Graduate Program Faculty

Bio

Dr. Alejandro received her Ph.D. in Physiology from the University of British Columbia.

Research Summary

Diabetes and metabolism roles of O-linked GlcNAc Transferase (OGT) signaling in pancreatic beta-cell development and programming of beta-cell susceptibility to diabetogenic conditions.

Bio

Dr. Atsushi Asakura is an Associate Professor of Neurology and a faculty member of the Stem Cell Institute in the University of Minnesota Medical School. He also belongs to Paul & Sheila Wellstone Muscular Dystrophy Center in the Medical School. Education: Dr. Asakura received his Ph.D. at the Institute of Medical Science at the University of Tokyo Graduate School and the National Institute of Neuroscience in Tokyo with Dr. Yo-ichi Nabeshima where he learned the molecular biology of skeletal muscle differentiation. He trained at the post-doctoral level at the Fred Hutchinson Cancer Research Center in Seattle with Dr. Stephen J. Tapscott. His post-doctoral studies involved the transcription factors for skeletal muscle development during early embryogenesis. He trained at the senior post-doctoral level at McMaster University in Hamilton and the Ottawa Health Research Institute in Ottawa with Dr. Michael A. Rudnicki where he started projects on skeletal muscle stem cells that contribute to muscle regeneration.

Research Summary

Over the past 30 years, Dr. Asakura has studied the myogenic transcription factors and muscle stem cells with an emphasis on Duchenne muscular dystrophy (DMD) therapy. Since he was a graduate student and postdoctoral fellow in the laboratories of Drs. Yoichi Nabeshima, Stephen Tapscott and Michael Rudnicki, he has focused on MyoD gene regulation and muscle stem cells more than 60 peer-reviewed publications. His laboratory's goals include attempting to understand the molecular mechanisms controlling muscle satellite cell (muscle stem cell) self-renewal and differentiation, and to develop novel therapeutic methods for DMD. This also involves the stem cell niche associated with vasculature in normal and regenerating skeletal muscle. And, he has recently begun exploration of cell-based therapy with induced Pluripotent Stem Cells (iPSCs) toward muscular dystrophy model animals.

Vascular niche for satellite cell self-renewal, muscle regeneration and muscular dystrophy therapy:
For an effective form of therapy of DMD, both the muscle and the vasculature need to be addressed. To reveal the developmental relationship between DMD and vasculature, Dr. Asakura created mdx mice, an animal model for DMD, carrying Flt1 mutation with increased vasculature (Hum Mol Genet, 2010). Using the animal models, his study is the first showing that developmentally and pharmacologically increasing vascular density can rescue the dystrophic phenotype in DMD model mice (PLoS Genet, 2019). This approach might be also effective to treat Facioscapulohumeral muscular dystrophy (FSHD) (J Clin invest, 2020. These data suggest that increasing the vasculature in DMD may ameliorate the histological and functional phenotypes associated with this disease. A patent for this technology has been granted in 2018 (US Patent, 2018). In addition, he established a tissue clearing protocol for skeletal muscle. Using this protocol, he is the first to image murine whole skeletal muscle using confocal and two-photon microscopy (Methods Mol Biol, 2016), and demonstrate that satellite cells pattern the microvasculature to be in close proximity to them via VEGFA, keeps the satellite cells in a more quiescent state via Notch pathway, suggesting a beneficial cross-talk (Cell Stem Cell, 2018).

Circadian transcriptional regulation in muscle stemcells:
Dr. Asakura has dedicated much of his professional career to studying MyoD function during myogenesis and muscle regeneration, and he has published more than 30 original research articles related to MyoD since he was a graduate student. His first contributions to science as an independent investigator were to demonstrate: 1)that MyoD negatively regulates satellite cell self-renewal (PNAS, 2007) via a MyoD-mediated induction of apoptosis through microRNA-mediated Pax3 gene suppression (J Cell Biol, 2010): 2) that the CDK inhibitor p57 plays essential roles in muscle differentiation as a MyoD downstream gene(Elife, 2018): 3) that myogenesis is regulated by an isomerase activity of Fkbp5 (Cell Rep, 2018): 4) that the core circadian regulator Cry2 and Per2 which regulates MyoD and IGF2 expression promotes myoblast proliferation and subsequent myocytefusion to form myotubes in a circadian manner (Cell Rep, 2018; bioRxiv, 2020).Therefore, his hypothesis is that genetic modification of transplanted stem cells using a modification of MyoD cascade may be utilized to effectively treat DMD and improve musclefunction.

DMD therapy via induced Pluripotent Stem Cells(iPSCs):
Dr. Asakura also demonstrates that upon being infected with a retroviral vector expressing the four reprogramming factors, the satellite cell-derived myoblasts successfully gave rise to iPSC colonies. To the best of their knowledge, this study is the first showing that fully committed myogenic cells can be reprogrammed to iPSCs (Stem Cells. 2011). His hypothesis is that myoblast-derived iPSCs may maintain epigenetic memory of myogenic status, which might contribute to the higher myogenic differentiation potential. Recently, he established the blastocyst complementation to generate iPSC-derived skeletal muscle in chimeric animals (World Patent Application, 2016). A key to the generation of human myogenic cells and skeletal muscle in a host animal is the selective knockout of genes in the blastocyst that are critical for organ development. These concerted approaches will help us to create iPSC-derived myogenic cells in vivo, which can be transplanted into patients for a definitive cure of DMD. In addition, the generation of iPSC-derived DMD skeletal muscle in mice will serve as an animal model to study the characteristics and regeneration of the human skeletal muscle diseases and responses to pharmacological agents such as exon-skipping.

Research Summary

My laboratory is primarily interested in metabolic physiology, stress physiology and social determinants of health and aging. We developed a unique integrative approach to investigate the molecular physiology of obesity and chronic stress-related disease which combines behavioral and genetic models, metabolic, neuroendocrine and imaging techniques in living animals as well as sophisticated molecular and structural biology analyses of neuropeptides.
The major research topics include: 1) the functional role of Vgf-derived peptides in obesity and metabolism and their development as innovative drug targets for obesity-related disease; 2) autonomic nervous system regulation of white and brown adipocyte functions in obesity; 3) stress-induced cardiovascular and metabolic diseases; 4) social determinants of health, disease and aging.
Funding sources include: NIDDK, NIA, NHLBI and several Foundations

Research Summary

My lab seeks to develop a quantitative, system-level understanding of stress response pathways at multiple scales -- from individual cells to whole organisms. Much of our research focuses on cell stress responses mediated by the tumor suppressor protein p53. We have used long-term time-lapse imaging to show that p53 undergoes complex dynamics in response to different forms of DNA damage. For example, in response to DNA double-strand breaks p53 levels increase and decrease in oscillations of fixed amplitude, duration, and frequency. In contrast, in response to UV-induced DNA damage p53 levels increased in a single pulse with a duration and amplitude that increases with decreasing damage. We have identified the specific molecular mechanisms that regulate the distinct p53 dynamical modes. By using small molecule inhibitors to alter p53 dynamics, we can change the transcriptional program regulated by p53 and thereby control individual cell fates.
Our current work focuses on developing a more integrated, network-level view of the regulation and function of p53 dynamics in single cells. We focus on identifying the molecular details by which p53 dynamics regulate downstream damage response pathways, including those regulating cell cycle arrest, DNA repair, senescence, apoptosis, and metabolism. We aim to identify how specific p53 pulse characteristics (amplitude, duration, or frequency) encode information that is decoded at the promoters of transcriptional targets. We are also applying quantitative, single-cell approaches to identify novel modes of regulation between p53 and other important signaling pathways, including the MYC proto-oncogene network and MAPK signaling. By developing a more quantitative understanding of these important signaling pathways, we hope to not only increase our basic understanding of these signaling dynamics in regulating cell fate decisions, but also provide novel methods for chemotherapeutic manipulation of signaling dynamics to alter cell fate in cancers in which the pathways are deregulated.
 

Bio

Dr. Bellin completed her pediatric residency and pediatric endocrine fellowship training at the University of Minnesota, and joined the faculty in 2009, with a joint appointment in Pediatrics and Surgery. Dr. Bellin's research focus is islet transplantation (transplantation of the insulin producing cells of the pancreas) for patients with type 1 diabetes mellitus and for patients who have their pancreas removed to treat severe chronic pancreatitis. She provides care for children with diabetes or general endocrine disorders at M Health Maple Grove Clinic and for islet transplant recipients at the University site.

Research Summary

Total Pancreatectomy Islet Auto Transplant, Chronic Pancreatitis

Clinical Summary

Chronic Pancreatitis, TPIAT, T1DM, General Endocrine

Bio

Bryce A. Binstadt, MD, PhD, is an Professor of Pediatrics in the Division of Pediatric Rheumatology, Allergy, and Immunology and a Distinguished University Teaching Professor. Dr. Binstadt cares for children with arthritis, systemic lupus erythematosus, dermatomyositis, and related rheumatologic disorders. He heads a laboratory in the University of Minnesota's Center for Immunology focused on understanding the pathogenesis of autoimmune diseases with particular emphasis on immune-mediated cardiovascular disease. He is the Director of the Pediatric Rheumatology Fellowship Training Program, an Associate Director of the Medical Scientist Training Program (MD/PhD), and Director of the Pediatric Physician Scientist Training Program.

Dr. Binstadt received his MD degree from Mayo Medical School and his PhD in Immunology from Mayo Graduate School in Rochester, MN. He then completed his residency in the Boston Combined Residency Program in Pediatrics at Boston Children's Hospital and Boston Medical Center, followed by fellowship training in Pediatric Rheumatology at Boston Children's Hospital. He served as an attending physician in the Rheumatology Program at Boston Children's Hospital/Harvard Medical School as well as a research fellow in the Section on Immunology and Immunogenetics at the Joslin Diabetes Center for two years before joining the faculty at the University of Minnesota in 2007. Dr. Binstadt is board-certified in Pediatrics and Pediatric Rheumatology.

Research Summary

Autoimmunity, Innate Immunity
The Binstadt Laboratory is broadly interested in autoimmune disease pathogenesis.

One main line of investigation focuses on how systemic autoimmune diseases lead to cardiovascular inflammation and damage. We use the K/BxN T cell receptor (TCR) transgenic mouse model. K/BxN mice spontaneously develop both inflammatory arthritis and autoimmune valvular carditis. We use this model to study the effector pathways driving the cardiac valve inflammation. Current projects seek to understand the key contributions of macrophage subsets and cytokines in this model.

A second line of research focuses on the potential role of dual TCR T cells in the development of autoimmune diseases. Ongoing projects are focused on a) the contribution of dual TCR T cells to type I diabetes and other autoimmune diseases and b) engineering a dual TCRα reporter mouse.

Finally, new projects seek to understand the contribution of the nervous system to inflammatory arthritis, using the K/BxN serum-transferred arthritis model.

Current Funding Sources:

• National Institutes of Health (NIH)
• American College of Rheumatology/Rheumatology Research Foundation

Clinical Summary

Juvenile dermatomyositis; Juvenile rheumatoid arthritis; Pediatric autoimmune diseases; Systemic lupus erythematosus

Research Summary

Age is associated with increased inflammation, visceral adiposity and metabolic disease. Tissue resident immune cells are required for dampening inflammation and maintaining tissue homeostasis. There are changes in resident immune cells that drive the increased inflammation and metabolic impairments that are seen with increased age. We are studying the cellular and molecular changes within tissue resident immune cells that drive metabolic impairments in tissues. In particular, we are focused on lipolysis, a metabolic process that is required for release of energetic substrates from stored triglycerides in adipocytes. Lipolysis is impaired in aged individuals and this impairment may contributes to a worsened ability of elderly to maintain a healthy body-weight, stay warm or exercise. Our work has previously shown that adipose tissue immune cells reside in microenvironment niches and are able to inhibit lipolysis in the aged adipose tissue. There are two broad projects within the lab: Adipose tissue macrophage-specific regulatory effects on lipolysis and inflammation during aging Fat-associated lymphoid cluster (FALC) and lymphocyte regulation of metabolism Our lab focuses on mouse models of aging and uses a wide variety of techniques to investigate the changes occurring with age. We combine this in vivo approach with a complementary in vitro cell culture system to better understand a direct mechanism. Ultimately, our goal is to generate candidates that could be targets for therapeutically treating to improve health span and restore metabolism in the elderly.

Bio

Dr. Sunny Chan is an Assistant Professor in the Department of Pediatrics, Division of Blood and Marrow Transplant & Cellular Therapy. Dr. Chan received his BSc in Pharmacology (1998) and BASc in Computer Engineering (2001) from the University of British Columbia, Canada, and PhD in Pharmacology from the Chinese University of Hong Kong in 2005. He did his postdoctoral fellowship at the National Cheng Kung University, Taiwan, and at the University of Minnesota in the laboratory of Dr. Michael Kyba. Dr. Chan joined the faculty of the University of Minnesota in 2015.

Research Summary

Dr. Chan’s research focuses on regenerative medicine for muscular dystrophies using cardiac and skeletal myogenic progenitors derived from pluripotent stem cells. He is developing methods to model cardiopharyngeal mesoderm, a cell population that forms second heart field and head muscle cells. The goal is to produce cell types appropriate for studying the physiology of muscular dystrophies specific to second heart field and head muscles in vitro and for developing cellular therapy targeting these diseases in vivo.

Bio

Administrator Info
Email: endofixer@umn.edu
Fax: 612-626-3133
Mail: 420 Delaware Street SE, MMC 101, Minneapolis, MN 55455

Summary
Dr. Lisa Chow finished medical school at the University of Minnesota in 1999 and completed an internal medicine residency and endocrinology fellowship at the Mayo Clinic. She joined the faculty at the University of Minnesota in 2006 and completed a Master's in Clinical Research in 2011. Dr. Chow is actively engaged in clinical research and is especially interested in the effects of lifestyle intervention (dietary changes, exercise) to treat insulin resistance and diabetes. She is also highly interested in mentoring the next generation of scientists by serving as the Director of the T32 training program for Diabetes, Endocrinology and Metabolism at the University of Minnesota.

Research Summary

The effects of lifestyle changes (diet, exercise) on insulin resistance and diabetes

Clinical Summary

Bone; Diabetes; Osteoporosis

Bio

Administrator Info
Name: Kelly LaPara
Email: schot014@umn.edu
Mail: 420 Washington Ave SE, MMC 194, Minneapolis, MN 55455

Summary
Obesity and cardiovascular disease are among the leading causes of morbidity and mortality worldwide. Our research focuses on the interplay between intermediary metabolism and these disease processes. Derangements in the processing of carbohydrates, fats, and amino acids are central drivers of disease pathogenesis, but the roles of another metabolic fuel class, ketone bodies, are less well understood. We use novel genetic mouse models with engineered deficiencies in ketone body metabolism to study the metabolic shifts that occur in response to obesity, cardiovascular disease, and dynamic environmental challenges. From these models, we have developed new perspectives of how metabolism adapts in obesity, diabetes, nonalcoholic fatty liver disease (NAFLD/NASH), and cardiomyopathy; how these adaptations ultimately prove deleterious, and how innovative and personalized nutritional and pharmacological therapies may mitigate these adverse responses.

We leverage recent advances in stable isotope tracer based NMR and mass spectrometry-based untargeted metabolomics technologies to study metabolism on a systems level, and we also employ established techniques in molecular cell biology and biochemistry to reveal phenotypic shifts at the cellular level. Complex in vivo phenotyping methodologies are strategically aligned with these sophisticated chemical profiling platforms to generate high resolution phenotypic pictures. In addition to our mouse studies, we perform studies in humans to learn how alterations of ketone metabolism and related pathways may serve as diagnostic biomarkers and therapeutic targets for obesity, diabetes, NAFLD/NASH, heart failure/CHF, and metabolic maladaptations that can occur in any disease state.

Teaching Summary

Metabolic Biochemistry

Clinical Summary

Heart Failure

Bio

Awards & Recognition

• Helen May Bradley Alumni Achievement Award, Maryville University of St. Louis, 2014
• Craig H. Neilsen Fellowship in Spinal Cord Injury Research, 2013-2015
• Bryan Robinson Neuroscience Endowment Doctoral Research Grant, 2010
• University of Florida Medical Guild Research Incentive Award, 2008

Professional Associations

• American Physiological Society
  • Central Nervous System Section 
• American Physical Therapy Association 
  • Research Section 
  • Academy of Neurologic Physical Therapy (formerly - Neurology Section)

Teaching Summary

Academic Interests and Focus

As an Assistant Professor in the Division of Physical Therapy, Dr. Brendan Dougherty is active in training students and serves on the Admissions Committee and New Faculty Search Committee.

Bio

Administrator Info
Name: Mayna Xiong
Email: xion2253@umn.edu
Mail: 2231 6th Street SE
4-141 CCRB
Minneapolis, MN 55455

Summary
Prior to his position with the U of MN, he served as Chief of Cardiology at Brown University in Rhode Island. Previously, he served as Chief of Cardiology and co-director of the Center for Cardiovascular Research at the University of Illinois at Chicago.

He received his MD/PhD degrees from the Medical College of Virginia, Virginia Commonwealth University, in Richmond, Virginia. He completed his residency, postdoctoral fellowship and cardiology fellowship at the University of Chicago in Chicago, Illinois. He serves on several editorial boards for publications including the Journal of the American College of Cardiology. Dr. Dudley is a fellow of the American College of Cardiology and the American Heart Association and is a member of the Association of University Cardiologists, the American Society for Clinical Investigation, the Heart Rhythm Society, the Cardiac Electrophysiology Society, and the Cardiac Muscle Society, among others. His research interests include arrhythmias and diastolic heart failure.

Research Summary

• Diastolic heart failure
• Sudden cardiac death

Research Funding Grants

• NIH Grant Number: 1 T32 HL144472-01A1
  PI: Crawford, Peter A & Samuel Dudley, M.D., Ph.D. (Contact)
  Project Title: Training Program in Cardiac Innovation
• NIH RePORTER ID: 1R01HL134791-01A1
  PI: Samuel C. Dudley, M.D., Ph.D.
  Project Title: Unfolded Protein Response and Arrhythmias
• NIH RePORTER ID: 1R01HL136757-01
  Sub PI: Samuel C. Dudley, M.D., Ph.D.
  Project Title: Regulation of Mitochondrial Calcium Uniporter in the Heart

Clinical Summary

Cardiac arrhythmia, Arrhythmia, Heart failure, Heart failure with preserved ejection fraction

Research Summary

My laboratory primarily studies the structure and cellular function of the dystrophin-glycoprotein complex, which spans the muscle cell plasma membrane (or sarcolemma) and links the cortical actin cytoskeleton with the extracellular matrix. Greater understanding of the physiologic role of the dystrophin-glycoprotein complex is necessary to understand how its absence or abnormality leads to Duchenne muscular dystrophy and forms of human dilated cardiomyopathy. The lab has defined the complete actin-binding region of 400 kDa dystrophin and shown that its homologue utrophin binds actin filaments through a distinct molecular mechanism. Novel methods to visualize the sarcolemmal cytoskeleton without interference from internal structures provided the first evidence that dystrophin functions in vivo to mechanically stabilize ?-actin filaments in costameres. Studies of dystrophin-deficient mice and new animal models generated by the lab have provided insight into the function of costameres in striated muscle and suggest novel links between dystrophin deficiency and alterations in cell signaling, or gene expression manifest by dystrophic muscle. My lab's unique capability to express biochemical amounts of full-length dystrophin and utrophin has made possible new studies to i) characterize the effects of dystrophy-causing point mutations on dystrophin structure/function, ii) to identify novel associated proteins and iii) to develop new protein-based therapies for dystrophinopathies. In a completely new line of investigation, my group is working to determine the potentially unique roles of non-muscle actin isoforms in the establishment/maintenance of cell polarity in a variety of tissues. The ?- and ?-isoforms of actin distribute to distinct locations within a variety of polarized cell types, including neurons, epithelial cells, and hair cells of the inner ear yet ?- and ?-actin differ from each other by only 4 amino acids. Using new isoform-specific reagents and conditional knock-out mouse lines developed during the course of our muscular dystrophy studies, the lab is now working to identify non-overlapping functions of these two highly conserved and widely expressed proteins.

Bio

Dr. Kotz's training and background are in basic science obesity research. Her Ph.D. research was done in the area of neuropeptide regulation of feeding and energy expenditure, including effects on circulating hormones and enzymatic activity in white and brown adipose tissue. Cathy's post-doctoral research involved the role of orexin in body weight regulation and orexin's effects on learning and memory during aging.

Research Summary

Our laboratory focuses on brain sites and substrates mediating energy balance, in obesity prone and obesity-resistant animal models. The goal of our laboratory is to understand brain mechanisms important in determining the popensity for obesity. These investigations involve study of neuropeptides that regulate feeding behavior and energy expenditure, including that related to physical activity. Our most recent focus is on the role of orexin, also known as hypocretin. Orexin is a recently identified neuropeptide predominantly located in the lateral hypothalamus that enhances feeding and physical activity, and which also modifies sleep/wake patterns. Our laboratory has shown that orexin elevates non-volitional low-level activity, which has an important impact on body weight control. We have also shown that this low level activity may be important in maintaing obesity resistance during aging. The techniques we use include stereotaxic surgery, immunohistochemistry, food intake measurements, physical activity chamber measurements, indirect calorimetry, body composition (EchoNMR) radioimmunoassay and molecular biology procedures, including RNA/DNA extraction, northern blots, slot blots, rtPCR, cDNA probe synthesis, random primer labeling, hybridization, densitometry and microarrays.

Bio

Administrator Info
Name: Lisa Moe
Email: seif0046@umn.edu
Mail: Cancer & Cardiovascular Research Building
2231 6th St SE, 1st floor Mailroom CCRB
Minneapolis, MN 55455

Summary
The Garry lab has two major areas of focus. The first area of focus is the neural control of cardiovascular responses to exercise. Specifically, the lab focuses on the Exercise Pressor Reflex which is a reflex activated by skeletal muscle contraction. The Garry lab has developed novel rodent models (rat and mouse) to explore the mechanisms that mediate this reflex in both physiological and pathological states. Abnormal function of this reflex occurs in a variety of diseases such as heart failure, hypertension, and diabetes and extreme abnormalities serves as a poor prognostic indicator. The goal of the lab is to identify specific mechanisms that underlie the abnormal reflex in various disease such that normalization of the reflex can be targeted with novel therapies. The second area of focus for the Garry lab is the generation of humanized organs for 1) novel human research models and 2) transplantation purposes. To that end, we have generated several models in which pigs develop humanized organs. Specifically, we have developed pigs with human skeletal muscle and pigs with human blood vessels and blood. These models will be used to generate unique research models and even allow for a new form of clinical trial without human risk. Additionally, we are developing organs for human transplantation purposes that will treat injury based deficits such as volumetric muscle loss. Moreover, these technologies can treat peripheral artery disease and can help to meet the staggering demand for human blood and platelets.Come work with us! Visit https://med.umn.edu/lhi/about/jobs to see open positions in the Mary Garry lab.

Research Summary

• Neural control of cardiovascular responses to exercise
• Generation of humanized organs for 1) novel human research models and 2) transplantation purposes

Bio

Administrator Info
Name: Lisa Moe
Email: seif0046@umn.edu
Mail: Lillehei Heart Institute
2231 6th Street SE
1st floor Mailroom CCRB
Minneapolis, Minnesota 55455

Research Summary

Regenerative medicine, Cardiogenesis, and Stem-Cell BiologyDan's laboratory has a long-standing interest in regenerative and stem cell biology with a focus on the heart and skeletal muscle. In their studies of the heart and skeletal muscle, the Garry laboratory utilizes an array of technologies including gene disruption strategies, transgenesis, single cell genome analysis, gene editing (TALEN and CRISPR technologies), inducible ES/EB model systems, hiPSC technologies, FACS and other cellular, biochemical and molecular biological techniques. In addition, their use of lower organisms such as zebrafish and newt, which are highly regenerative model systems have successfully uncovered critical regenerative factors. Human iPSCs are another important model for cardiovascular disease investigation for the lab. Using these technologies, the Garry lab was among the first to discover the molecular markers of stem cell populations that regulate critical networks during heart and skeletal muscle development and regeneration. For example, their studies have uncovered novel Ets and Forkhead transcription factors, microRNAs and signaling pathways that direct fate determination of stem cell populations. The manipulation of these pathways using chemical genetics and molecular technologies has provided a platform focused on rebuilding and repairing the injured heart and skeletal muscle. Care Philosophy My philosophy is to provide outstanding comprehensive care to patients with cardiovascular disease, including a number of emerging technologies available at the University of Minnesota Medical Center-Fairview. My practice combines state-of-the-art therapies, compassion, and effective communication, creating a working partnership that results (overall) in high quality of life for my patients.

Clinical Summary

General cardiology; Advanced heart failure; Orthotopic heart transplant

Bio

Dr. Curtis Hughey, PhD, completed his doctoral studies at the University of Calgary in Biochemistry and Molecular Biology. During his doctoral training he received a Canadian Institutes of Health Research Doctoral Scholarship and the Izaak Walton Killam Memorial Scholarship to study the use of stem cell therapy to promote in vivo insulin sensitivity in mouse models of diet-induced obesity and heart failure. With an interest in the genetic and environment regulation of in vivo glucose control, Dr. Hughey then pursued a postdoctoral fellowship at Vanderbilt University. While at Vanderbilt, he received a Canadian Diabetes Association Postdoctoral Fellowship to test the role of liver energy state in the regulation of glucose production during exercise. This work employed a metabolic flux analysis technique that uses stable isotopes, mass spectrometry, and computational modeling to quantify in vivo metabolic fluxes. An emerging research focus for the Hughey Laboratory at the University of Minnesota is to define the role of transmethylation in the metabolic reprogramming that occurs in non-alcoholic fatty liver disease and hepatocellular carcinoma.

Research Summary

Metabolic dysregulation underlies many public health challenges of modern society. The overarching objective of research in the Hughey Laboratory is to identify pathways within complex metabolic networks that can be used for early identification of disease or targeted to prevent or treat metabolic diseases. To accomplish this aim, studies combine the use of stable isotopes, mass spectrometry, and computational modeling to quantify in vivo metabolic fluxes in genetically-engineered mice. Many studies also employ provocative stimuli such as exercise and diet to challenge metabolic networks. Areas of focus are: The role of dysregulated hepatic transmethylation in the metabolic programming that promotes non-alcoholic fatty liver disease and hepatocellular carcinoma. Regulation of hepatic glucose formation during acute exercise and in response to habitual exercise.

Bio

To learn more about Dr. Iaizzo's research, please visit the Visible Heart Laboratories website.

Research Summary

Translational Systems Physiology Physiology of skeletal and cardiac muscle (in vivo, in situ and in vitro); Medical device design. Cardiac Anatomy: http://www.vhlab.umn.edu/atlas Pathophysiology of human skeletal muscle. Effects of anesthetic agents on the function of extrafusal and intrafusal skeletal muscle and cardiac muscle. Development of novel instrumentation and biomedical devices for physiological monitoring, clinical evaluation and/or therapeutic use. Role of elevated intracellular [Ca2+] in: 1) cell signaling; 2) dystrophic processes within skeletal muscle; and 3) cell toxicity. Physiological and pathological oscillations of the musculoskeletal system (e.g., tremor, shiver and clonus). Physiology of thermoregulation and biomedical applications of heat transfer in humans. Non-invasive and invasive correlates of wound formation, status, healing and prevention: development of animal models, and the design of biomedical instrumentation. Cervical and lumbar spinal cord biomechanics and management of back pain.

Bio

Peter B. Kang, MD, FAAN, FAAP is a pediatric neuromuscular neurologist and physician-scientist whose laboratory studies the genetics of muscular dystrophy and mechanisms of rare muscle diseases, with the goal of discovering new therapeutic targets for these diseases. He also studies DNA repair disorders including Cockayne syndrome and xeroderma pigmentosum.  He has published extensively on these subjects, has co-edited a textbook of pediatric electromyography, and has been awarded multiple grants from the NIH and the Muscular Dystrophy Association to support his investigations. With support from the CDC, he led the successful initiation of the first site in Florida for the MD STARnet consortium and continues to work on this project. He is an associate editor of Muscle & Nerve and serves on the editorial board of Neurology. National presentations include lectures on pediatric neuromuscular topics at the annual meetings of the American Academy of Neurology, American Academy of Pediatrics, American Association of Neuromuscular and Electrodiagnostic Medicine, the Child Neurology Society, and the Muscular Dystrophy Association. His former trainees hold faculty positions in the United States, Canada, South Korea, and Japan.  He is President of the Child Neurology Society.

Previously, Dr. Kang was Professor of Pediatrics, Chief of the Division of Pediatric Neurology, and Director of the Child Neurology Residency Program at the University of Florida College of Medicine. Earlier in his career, he was Director of the Electromyography Laboratory at Boston Children's Hospital and Associate Professor of Neurology at Harvard Medical School.

In clinic, Dr. Kang sees children with confirmed or suspected neuromuscular disorders such as muscular dystrophy, congenital myopathy, neuropathies, brachial plexus injuries, spinal muscular atrophy, and myasthenia gravis, as well as children with DNA repair disorders such as Cockayne syndrome and xeroderma pigmentosum. He will see adult patients with these conditions upon request.

Bio

Awards & Recognition

• National Institutes of Health Loan Repayment Program (LRP), competitive Renewal, 2019
• Faculty Success Program, National Center for Faculty Development, 2018
• National Institutes of Health Loan Repayment Program (LRP), 2017
• NIKE, Inc. Loren G. Myhre Environmental and Exercise Physiology Postdoctoral Research Award, EEP Section of the American Physiology Society, 2015
• Recognition Award for Beginning Investigators (Exercise and Environmental Physiology, EEP) section of the American Physiological Society, 2014
• Promotion of Doctoral Studies (PODS II) Scholarship from the Foundation of Physical Therapy, Marquette University, 2010
• Canadian Institutes of Health Research (CIHR) Research Award, McMaster, 2008
• Clinical Excellence Award, Marquette University, 2006

Professional Associations

• American Heart Association
• American Physical Therapy Association
• American Autonomic Society   
• American College of Sports Medicine, Member
• American Physiology Society, Member
  • Exercise and Environmental Physiology Section Member
  • Cardiovascular Section Member

Research Summary

The Cardiovascular Research and Rehabilitation Laboratory (CRRL) has a primary interest to investigate 1) factors that contribute to the greater cardiovascular risk in women after menopause and 2) exercise intolerance in those with cardiovascular and pulmonary disorders. In addition, we aim to develop novel treatment strategies to improve cardiorespiratory regulation and decrease cardiovascular disease.

The CRRL uses a multi-system approach to understand blood pressure regulation as the maintenance of blood pressure at rest and during exercise involves a highly redundant and sophisticated integration of multiple systems with the goal of maintaining homeostasis. Our laboratory uses several techniques to quantify autonomic function and limitations to exercise in healthy and clinical populations, such as those with cardiovascular diseases and muscular dystrophy. Techniques in our lab to quantify autonomic function are muscle sympathetic nerve activity (MSNA), which is the gold standard for measuring sympathetic activity, electrocardiography, heart rate variability, baroreflex function and venous occlusion plethysmography to measure limb blood flow. Our laboratory is also interested in limitations to exercise, including cardiopulmonary and skeletal muscle factors in healthy and clinical populations. We conduct maximal/peak oxygen consumption (VO_2max/peak)tests as well as fatigability tests isolated to single muscle groups. We aim to understand the contributing factors of autonomic dysregulation to cardiovascular disease and identify optimal treatment strategies to reduce cardiovascular risk and mortality in adults.

Current projects

• Mechanisms of increased cardiovascular disease risk in women who enter menopause premature or early
• Influence of menopausal symptoms, including hot flashes and sleep disturbance, to autonomic blood pressure regulation.
• Mechanisms of exercise intolerance in clinical populations including muscular dystrophy and heart failure
• The contribution of locomotor muscle afferents (group III and IV) to central drive and cardiorespiratory responses during exercise in both healthy adults and those with heart failure
• Use of neuromodulation to improve blood pressure in clinical populations.

Research Funding Grants

Institute of Engineering Medicine Working Grant University of Minnesota 
Working group to establish Autonomic Neuromodulation.
Role: Co-PI (Osborn-PI) 
2/2019-12/2020

Grant-In-Aid, University of Minnesota 
Autonomic blood pressure regulation in older premature and early menopause 
The goal of this GIA is to determine autonomic regulation of blood pressure in older women who entered menopause premature or early.
Role: PI
1/2020-6/2021

1 K01 AG064038-01A1, National Institute of Health
Autonomic blood pressure regulation in older premature and early menopause 
The goal of this Career Development grant to study autonomic blood pressure regulation in premature and early post-menopausal women.
Role: PI
5/2020-4/2025

Women’s Health Research Program, University of Minnesota (Keller-Ross-PI)
Sympathetic activity and baroreflex function in postmenopausal black females
The goal of this study is to investigate the differences in blood pressure regulation in typical age and premature/early menopause in black females.
Role: PI
10/2020-10/2021

Publications

2021

• Vera, K, McConville, Kyba, M, Keller-Ross, ML. Resting Metabolic Rate in Adults with Facioscapulohumeral Muscular Dystrophy. Appl Physiol, Nutr, Metab (2021). Mar 18. doi: 10.1139/apnm-2020-1119. PMID: 33735584.
• Anderson, E, Kelly, T, Sharp, A, Keller-Ross, ML, Brunsvold, ME. (2021) Active Rehabilitation in a patient during and after venovenous extracorporeal membrane oxygenation with a diagnosis of COVID-19, a case report. J Acute Care Phys Ther (In Press).
• Keller-Ross, ML, Chantigian, DP, Nemanich, S, Gillick, BT. (2021) Cardiovascular effects of transcranial direct current stimulation and bimanual training in children with cerebral palsy. Pediatric Physical Therapy Journal. Jan 1;33(1):11-16. DOI: 10.1097/PEP.0000000000000762.

2020

• Smith, JR, Joyner, MJ, Curry, TB, Borlaug, BA, Keller-Ross, ML, Van Iterson, EH, Olson, TP. In press. Locomotor Muscle Group III/IV Afferents Constrain Stroke Volume and Contribute to Exercise Intolerance in Human Heart Failure. J Physiol.
• Keller-Ross, ML, Chantigian, DP, Nemanich, S, Gillick, BT. In press. Cardiovascular effects of transcranial direct current stimulation and bimanual training in children with cerebral palsy. Pediatric Physical Therapy Journal. 
• Vera, K, McConville, Kyba, M, Keller-Ross, ML. (2020) Sarcopenic obesity in Facioscapulohumeral Muscular Dystrophy. Frontiers in Physiology. doi.org/10.3389/fphys.2020.01008. 
• Keller-Ross, ML, Cunningham, HA, Carter, JR. (2020) Impact of age and sex on neural cardiovascular responsiveness to cold pressor test in humans. Am J Physiol Regul Integr Comp Physiol. doi: 10.1152/ajpregu.00045.2020 
• Lalande, S. Cross, TT, Keller-Ross, ML, Morris, N, Johnson, BD, Taylor, BJ (2020) Exercise Intolerance in Heart Failure: Central Role for the Pulmonary System. Exercise and Sport Sciences Reviews. Jan;48(1):11-19.doi: 10.1249/JES.0000000000000208

2019

• Keller-Ross ML, Larson, M, Johnson, BD. Skeletal Muscle Fatigability in Heart Failure (2019). Frontiers in Physiology. Feb 21;10:129. doi:10.3389/fphys.2019.00129.
• Keller-Ross ML, Chantigian DP, Rich TL, Chen M, Chen CY, Gillick BT. Stability of the cardiovascular response during single-pulse TMS in perinatal stroke. (2019) Brain Stimul. pii: S1935-861X(18)30376-0. doi: 10.1016/j.brs.2018.11.010. 

2018

• Keller-Ross ML, Chantigian DP, Rich TL, Chen M, Chen CY, Gillick BT. Stability of the cardiovascular response during single-pulse TMS in perinatal stroke. Brain Stimul. (2018) Nov 20. pii: S1935-861X(18)30376-0. doi: 10.1016/j.brs.2018.11.010. 
• Keller-Ross, ML, Sarkinen, AL, Chantigian, DP, Cross, TJ, Johnson, BD, Olson, TP. Interaction of Chemoreflex and Ergoreflex during Dynamic Exercise in Healthy Adults. (2018). Translational Sports Med. doi.org/10.1002/tsm2.60. 
• Keller-Ross, ML, Chantigian, Dl, Evanoff, N, Bantle, Anne, Dengel, Donald, Chow, Lisa (2018). VE/VCO2 slope in Lean and Overweight Women and Its Relationship to Lean Leg Mass. Int J Cardiol Heart & Vasculature.

2017

• Ann Van de Winckel, Yu-Ting Tseng, Daniel Chantigian, Kaitlyn Lorant, Zinat Zarandi, Jeffrey Buchanan, Thomas A. Zeffiro, Mia Larson, Becky Olson-Kellogg, Jürgen Konczak, Manda L. Keller-Ross (2017). Age-Related Decline of Wrist Position Sense and its Relationship to Specific Physical Training. Front Hum Neuroscie.;11:570. 
• Wheatley, Courtney M., Baker, Sarah E, Taylor, Bryan J, Keller-Ross, Manda L. Chase, Steven C, Carlson, Alex R., Wentz, Robert J. Snyder, Eric M, Johnson, Bruce D. Influence of Inhaled Amiloride on Lung Fluid Clearance in Response to Normobaric Hypoxia in Healthy Individuals. (2017) High Altit Med & Biol.; 18:4: 343-354.

2016

• Keller-Ross, ML, Cowl, A, Cross, TJ, Johnson, BD, Olson, TP. (2016). Ventilation Increases with Lower Extremity Venous Occlusion in Young Adults. Med Sci Sports Exerc, 48 (3): 377-383.

2015

• Keller-Ross, ML, Johnson.BD, Carter, R, Joyner, MJJ, Eisenach, J, Curry, T, Olson, TP. (2015). Improved Ventilatory Efficiency with Locomotor Muscle Afferent Inhibition is Strongly Associated with Leg Composition in Heart Failure. Int J Cardiol, 202: 159-166.
• Cross TJ, Keller-Ross ML, Issa A, Wentz R. Taylor B, Johnson B. (2015). The impact of averaging window length on the desaturation indexes obtained via overnight pulse oximetry at high altitude. Sleep, 38(8): 1331-1334.

2014

• Keller-Ross ML, Joyner, MJ, Johnson, BD, Olson, TP.(2014) Influence of the metaboreflex on arterial blood pressure in heart failure patients. Am Heart J, 167(4):521-8.
• Keller-Ross ML, Pruse, J, Yoon T, Schlinder-Delap B, Harkins, A & Hunter SK. (2014) Stress- Induced increase in muscle fatigability of young men and women is predicted by strength but not voluntary activation. J Appl Physiol, 116(7):767-768.
• Keller-Ross ML, Schlinder-Delap B, Doyel, R, Larson, G & Hunter SK. (2014) Muscle fatigability is greater in veterans with posttraumatic stress disorder. Med Sci Sports Exerc, 46(7):1302-13.

2011

• Yoon T, Schlinder-Delap B, Keller ML & Hunter SK (2011b). Supraspinal fatigue impedes recovery from a low-intensity sustained contraction in old adults. J Appl Physiol 112, 849- 858.
• Keller ML, Pruse, J, Yoon T, Schlinder-Delap B, Harkins, A & Hunter SK (2011). Supraspinal Fatigue in men and women during a low force fatiguing contraction. Med Sci Sports Exerc.43, 1873-1883.
• Pereira H, Keller ML (2011). Understanding the mechanisms of neuromuscular fatigue with paired- pulse stimulation. J Physiol 589 (Pt 14), 3533-3544.

2010

• Hoeger Bement M, Weyer A, Keller, ML, Harkins AL, Hunter SK (2010) Anxiety and stress can predict pain perception following a cognitive stress. Physiology & Behavior 101: 87-92.

2009

• Yoon T, Keller ML, Delap BS , Harkins A, Lepers R, & Hunter SK (2009). Sex differences in response to cognitive stress during a fatiguing contraction. J Appl Physiol: respiratory, environmental and exercise physiology 107: 1486-1496.
• Hoeger-Bement M, Rasiarmos R, DiCapo R, Lewis A, Keller ML, Harkins A, Hunter S (2009). The Role of the Menstrual Cycle Phase In Pain Perception Before and After an Isometric Fatiguing Contraction. Eur J Appl Physiol 106: 105-112. (PMID:19189119).

Teaching Summary

Physiology

Research Summary

My lab studies the role of mitochondria in generating, signaling, and responding to cellular stress, particularly in cardiac and skeletal muscle. In particular, we currently focus on how the dysregulation of mitochondrial calcium leads to physiological changes in mouse models. Mitochondrial calcium handling plays a critical role in energy production as well as cell death. To decipher the impact of calcium perturbation on multiple scales, our approaches span a variety of experimental techniques, from biochemical measurements on isolated mitochondria to live cell microscopy to in vivo phenotyping.

Bio

After completing undergraduate studies in biochemistry at SUNY College at Geneseo, Dr. Lou received his M.D. and Ph.D. degrees (Microbiology and Immunology) from SUNY Upstate Medical University in 2004. He performed his residency training in Internal Medicine at Duke University Medical Center and then subsequently completed his Medical Oncology and Hematology fellowship at the Memorial Sloan-Kettering Cancer Center in 2010. He also completed an additional fellowship in Neuro-Oncology at the Preston Robert Tisch Brain Tumor Center at Duke. Dr. Lou, a diplomate of the American Board of Internal Medicine, is board certified in Medical Oncology and Internal Medicine. In addition he is also board certified in Neuro-Oncology through the United Council for Neurologic Subspecialties. He joined the faculty in the Division of Hematology, Oncology and Transplantation in 2011 and is a member of the Masonic Cancer Center, University of Minnesota. Care Philosophy New Patients If you are scheduled or interested in scheduling a clinic consultation with Dr. Lou, click here for more information and a welcome from Dr. Lou. Tips to be a Great Patient Advocate Dr. Lou's interview with Caringbridge.org

Research Summary

Role of tunneling nanotubes in intercellular communication and pathophysiology of cancer.  Biomarkers of drug resistance in cancer Genomic markers of exceptional response or non-response to drug therapy in solid tumor malignancies (colorectal cancer and malignant brain tumors) 

Clinical Summary

Appendix Cancer; Neuroendocrine Tumors; Pancreatic Cancer; Esophageal Cancer; Gastric Cancer; Colorectal Cancer; Cancer Metastasis; Solid Tumor Metastasis to the Brain; Brain Tumors

Bio

Dr. Walter Low is a Professor in the Department of Neurosurgery and serves as the Associate Head for Research. He earned his PhD in Bioengineering from the University of Michigan, and was a National Science Foundation/NATO Fellow in Neurophysiology/Neuroscience at the University of Cambridge in England. He is currently Director of the Research Laboratories in the Department of Neurosurgery.

Dr. Low was formerly on the faculty at Indiana University School of Medicine where he was the Director of the Graduate Program in Physiology and Biophysics. He has served as a member of numerous grant review study sections for the National Institutes of Health, the National Science Foundation, and the Veterans Administration Medical Centers.

The h-index for the scientific impact of Dr. Low's research publications is ranked above the 95th percentile among faculty in neurosurgery departments in the United States.

Research Summary

Dr. Low's research is focused on translating neuroscience developments from the laboratory to the clinic. He has been involved in a number of technologies that include neural progenitor/stem cell therapies, gene therapies, neuroprotective therapies, and medical devices for treating a variety of neurological conditions. Neural disorders of interest include ischemic and hemorrhagic stroke, Parkinson's disease, brain tumors, Alzheimer's disease, lysosomal storage disorders of the brain, Huntington's disease, spinal cord injury, and traumatic brain injury.

Dr. Low's group was the first to: Demonstrate that the transplantation of cholinergic neurons into the hippocampal formation could restore learning and memory function in a rat model of Alzheimer's disease Demonstrate the efficacy of immunotherapy for eradicating intracranial tumors in rodents Receive FDA approval for clinical trials in the United States to study the efficacy of deep brain stimulation for the treatment of Parkinson's disease. Read more.

Brain and tumor immunology and development of cancer vaccines

Dr. Low's laboratory is focused on the study of brain tumors. Primary tumors that originate in the brain represent some of the most malignant types of cancers. Patients diagnosed with grade IV glioblastoma multiforme have a mean survival time of 11 months after diagnosis. Our studies of brain tumors have emphasized the development of immunotherapeutic approaches for the treatment of these tumors. Cancer vaccines consisting of cytokines and tumor antigens are used to stimulate cells of the immune system to recognize and destroy tumors within the brain.

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Bio

Expertise

Skeletal muscle biology in aging, health and disease

Professional Associations

• Fellow, American College of Sports Medicine
• Member, American Physiological Society
• Member, Institute on the Biology of Aging and Metabolism (iBAM), UMN
• Member, Paul and Sheila Wellstone Muscular Dystrophy Center, UMN

Research Summary

Dr. Lowe's laboratory investigates cellular and molecular mechanisms underlying skeletal muscle deterioration that occur with age, injury, and disease. We are particularly interested in how the loss of estradiol causes muscle weakness and impaired regeneration of injured muscles. Our studies point toward the deterioration of myosin function and satellite cells as two of the culprits. We are highly collaborative in muscular dystrophy research having published with eight other UMN muscle biologists. Our studies often have a flavor of exercise science and preventative medicine as well as rehabilitation. Trainee research experiences are enriched by the collaborative nature of our work that intersects muscle research from fields of biochemistry, physiology, biophysics, engineering, molecular and stem cell biology, pathology, endocrinology, immunology, and bone biology.

Research Funding Grants

• NIH, T32 AS007612-21 (MPI with Ervasti and Thomas)
  Minnesota Muscle Training Program
  05/01/2022-04/30/2027
• NIH, T32 AG029767-14 (MPI with Arriaga and Niedernhofer)
  Functional proteomics of aging training grant
  05/01/2019-04/30/2023
• NIH, R01 AG031743-12
  Interaction of Estrogen, Age and Activity on Musculoskeletal Strength in Females
  02/01/2009 - 01/31/2024
• NIH, R01 AG062899-2 (MPI with Michael Kyba)
  Dissecting Effects of Estrogen Deficiency on Satellite Cells on Muscle Regeneration in Females and Males
  10/01/2019 - 09/30/2024

Publications

2023:

Le G, Baumann CW, Warren GL, and Lowe DA (2023). In vivo potentiation of muscle torque is enhanced in female mice through estradiol-estrogen receptor signaling. J Appl Physiol (1985) 134(3):722-730. PMID: 36735234. PMC10027088.

2022:

Peyton MP, Tzu-Yi Y, Higgins L, Markowski TW, Vue C, Parker LL, Lowe DA (2022). Global phosphoproteomic profiling of skeletal muscle in ovarian-hormone deficient mice. Physiol Genomics 54(11):417-432. PMID 36062884. PMC9639773.

Norton A, Thieu K, Baumann CW, Lowe DA, Mansky KC (2022). Estrogen regulation of myokines that enhance osteoclast differentiation and activity. Scientific Reports 12:15900. PMID 36151243. PMC9508086.

Larson AA, Shams AS, McMillin SL, Sullivan BP, Vue C, Roloff ZA, Batchelor E, Kyba M, Lowe DA (2022). Estradiol deficiency reduces the satellite cell pool by impairing cell cycle progression. Am J Physiol Cell Physiol 322:C1123-C1137. PMID 35442828. PMC9169829.

Baumann CW, Ingalls CP, Lowe DA (2022). Mechanisms of weakness in mdx muscle following in vivo eccentric contractions. J Muscle Res 43(2):63-72. PMID 35445349.

Lin Y, Nhieu J, Liu P, Le G, Lee DJ, Wei C, Lin Y, Oh S, Lowe DA, Wei L (2022). CRABP1-CaMKII-Agrn regulates the maintenance of neuromuscular junction in spinal motor neuron. Cell Death Differ 29:1744-1756. PMID 35217789. PMC9433400.

McMillin SL, Minchew EC, Lowe DA, Spangenburg EE (2022). Skeletal muscle wasting: the estrogen side of sexual dimorphism. Am J Physiol Cell Physiol 322:C24-C37. PMID 34788147. PMC8721895.

Sidky SR, Ingalls CP, Lowe DA, Baumann CW (2022). Membrane proteins increase with the repeated bout effect. Med Sci Sports Exerc 54(1):57-66. PMID 34334717. PMC8678180.

2021:

Baumann CW, Lindsay A, Sidky SR, Ervasti JM, Warren GL, Lowe DA (2021). Contraction-Induced Loss of plasmalemmal electrophysiological function is dependent on the dystrophin glycoprotein complex. Front Physiol 12:757121. PMID 34764884. PMC8576390

Arpke RW, Shams AS, Collins BC, Larson AA, Lu N, Lowe DA, Kyba M (2021). Preservation of satellite cell number and regenerative potential with age reveals locomotory muscle bias. Skeletal Muscle 11:22. PMID 34481522. PMC8418011.

Trost JP, Chen M, Stark MM, Hodges JS, Richter S, Lindsay A, Warren GL, Lowe DA, Kimberley TJ (2021). Voluntary and magnetically evoked muscle contraction protocol in males with Duchenne muscular dystrophy: Safety, feasibility, reliability, and validity. Muscle Nerve 64:190-198. PMID 33974714.

Vang P, Baumann CW, Barok R, Larson AA, Dougherty BJ, Lowe DA (2021). Impact of estrogen deficiency on diaphragm and leg muscle contractile function in female mdx mice. PLoS ONE 16(3):e0249472. PMID 33788896. PMC8011782.

Lindsay A, Holm J, Razzoli M, Bartolomucci A, Ervasti JM, Lowe DA (2021). Some dystrophy phenotypes of dystrophin-deficient mdx mice are exacerbated by mild, repetitive daily stress. FASEB J 35(4):e21489. PMID 33734502.

Lindsay A, Kemp B, Larson AA, Baumann CW, McCourt PM, Holm J, Karachunski P, Lowe DA, Ervasti JM (2021). Tetrahydrobiopterin synthesis and metabolism is impaired in dystrophin-deficient mdx mice and humans. Acta Physiol (Oxf) 231(4):e13627. PMID 33580591.

Karvinen S, Juppi HK, Le G, Cabelka CA, Mader TL, Lowe DA, Laakkonen EK (2021). Estradiol deficiency and skeletal muscle apoptosis: Possible contribution of microRNAs. Exp Gero 147:111267. PMID 33548486.

Teaching Summary

Grant Writing: RSC 8206

Bio

Administrator Info
Mail: 6-155 Jackson Hall
1214A
321 Church St. SE
Minneapolis, MN 55455

Research Summary

Research in the Mashek laboratory focuses on the relationship between lipid metabolism and the development of metabolic and aging-related diseases. A primary emphasis is on studies involving lipid droplet biology in the context of non-alcoholic fatty liver disease, Type 2 Diabetes, cancer and aging. A major focus is on understanding how lipid droplets are catabolized and how they communicate within cells to influence cell function. We also conduct pre-clinical and clinical studies to determine how alterations in diet and dietary patterns (fasting, time-restricted feeding, etc.) and exercise alter metabolism to improve health.

Bio

Joseph M. Metzger, Ph.D., is the Maurice Visscher Land-Grant Chair of Physiology and Professor and Head of Integrative Biology and Physiology at the University of Minnesota Medical School. The Metzger laboratory uses molecular and integrative biomedical approaches for mechanistic investigations of heart and skeletal muscle function, with the long-range goal of translating these findings to new therapies and treatments for acquired and inherited heart and muscle diseases.
Metzger Lab Mission Statement: We seek mechanistic insights into normal and diseased cardiac and skeletal muscle function. Our overarching goal is to translate basic science discoveries into potential therapeutic strategies to combat inherited and acquired forms of heart and muscle diseases. Lab projects embrace individuality, emphasize cooperation and collaboration, and encompass a standard of excellence to all that we do as individual researchers and as a laboratory. Our guiding principles are to treat others with respect and courtesy, to maintain the lab in a collegial, safe and professional environment, and to work each day to the fullest of our capabilities.
Metzger received a Bachelor's degree in Natural Science from Saint John's University, Collegeville, Minnesota (1980), a Master's degree in Biology and Exercise Physiology from Ball State University, Muncie, Indiana (1982), a Ph.D. degree in Biology/Physiology under the mentorship of Dr. Robert Fitts from Marquette University Milwaukee, Wisconsin (1985), and performed post doctoral studies with Dr. Richard Moss at the University of Wisconsin, Madison, Wisconsin (1991). His lab designed and implemented a cardiac muscle-cell system that allows the transfer of genes into heart cells in order to assess the impact of those genes on the production of force and motion, the major function of cardiac muscle cells. The approach has the advantage of shedding light on the primary role of a normal or mutated gene in an otherwise normal muscle cell.
Metzger's findings have been published in top peer journals including Nature, Science, Nature Medicine, the Journal of Clinical Investigation, and the Proceedings of the National Academy of Sciences. This research is funded by the National Institutes of Health (NIH), the American Heart Association, the Muscular Dystrophy Association, and the Federation to Eradicate Duchenne, and has opened the path to treatment for a variety of heart and muscle diseases.

Research Summary

We are a mechanistically driven biomedical research lab focused on the form and function of heart and skeletal muscle in health and disease. We use molecular and integrative biomedical approaches for mechanistic investigations of heart and skeletal muscle function, with the long-range goal of translating these findings to new therapies and treatments for acquired and inherited heart and muscle diseases.Integrative systems biology of cardiac and skeletal muscle function Gene therapy, Gene and Base Editing Synthetic chemistries as membrane stabilizers Transgenic models of heart and muscle diseases Molecular mechanisms of sarcomere function Human iPS cell cardiac and skeletal muscle

Research Summary

My research career has been dedicated to investigating the impact of DNA damage on the structure of DNA, cell function and organism health. The DNA in each of our cells is damaged thousands of times per day by exposure to environmental factors, dietary components, chemotherapeutic agents and even endogenous by-products of normal metabolism. Studying patients with rare diseases caused by inherited defects in DNA repair provides important insight into the consequences of DNA damage. These patients have a dramatically increased risk of cancer and age prematurely. We engineered mouse models of these genome instability syndromes as a sensitive tool to test hypotheses about how DNA damage promotes cancer and aging.

Research Summary

Our laboratory focuses on G-protein coupled receptor (GPCR) signaling in the heart, with two main areas of emphasis.
1. Free fatty acid receptor 4 (Ffar4). Ffar4 is a G-protein coupled receptor for long chain fatty acids (Carbon chains 14-24) including omega-3 polyunsaturated fatty acids (omega 3-PUFAs). Clinically, omega 3-PUFAs improve outcomes in heart failure, but the mechanism is unclear. We previously demonstrated that eicosapentaenoic acid, or EPA an omega 3-PUFA, prevents heart failure in a mouse model but not through the traditional mechanism of membrane incorporation. Alternatively, we found that the cardioprotective effects of EPA might be mediated through Ffar4, an entirely novel molecular mechanism to explain the benefits of omega 3-PUFAs in the heart. Currently, our research is focused on understanding this novel role for Ffar4 as a cardioprotective nutrient sensor in the heart that responds to fatty acid composition to protect the heart from pathologic stress.
2. alpha 1-Adrenergic receptors (alpha 1-AR): alpha 1-ARs are receptors activated by the endogenous sympathetic catecholamines norepinephrine (produced in sympathetic nerve terminals) and epinephrine (produced in the adrenal gland). Clinically, alpha 1-ARs were originally used for the treatment of hypertension (HTN) and are currently used to treat benign prostatic hyperplasia (BPH). Clinical trials demonstrated that alpha 1-AR antagonists (doxazosin) worsened outcomes in patients with HTN, significantly increasing cardiac events and doubling the risk of heart failure. Our work has provided a mechanistic basis to explain the failure of alpha 1-blockers in patients with HTN, demonstrating that alpha 1-ARs in cardiac myocytes protect the heart from pathologic stress. Currently, our research is focused on understanding the molecular basis for the cardioprotective effects of alpha 1-ARs focusing on how differential subcellular compartmentalization of receptors affects their function. Further, based on our work on alpha 1-AR subcellular compartmentalization, we are developing a next-generation alpha 1-blocker for HTN without cardiac side-effects.

Bio

Administrator Info
Name: Esther Almeida
Email: ealmeida@umn.edu
Mail: 2231 6th Street SE
4-132
Minneapolis, MN 55455

Summary
Jin O-Uchi MD, PhD is Assistant Professor of Medicine at the Lillehei Heart Institute, Department of Medicine, Cardiology Division at the University of Minnesota. Dr. O-Uchi received the MD and PhD degree from Jikei University School of Medicine in Japan. He did a postdoctoral fellowship at University of Rochester and worked as an Instructor and a Research Assistant Professor at Thomas Jefferson University. Prior to his position with the U of MN, , he was at Cardiovascular Research Center at Brown University and Rhode island Hospital as an Assistant Professor of Medicine. His research potential has been recognized at a national level by grant awards from NIH/NHLBI, NIH/NIGMS, American Heart Association (AHA) and American Physiological Society (APS). He serves on several editorial boards for publications including Frontiers in Physiology; Frontiers in Cardiovascular Medicine; Frontiers in Genetics; Frontiers in Cell and Developmental Biology; World Journal of Cardiology; Journal of Biochemistry and Molecular Biology Research; and JSM Biochemistry and Molecular Biology. Dr. O-Uchi is a Fellow of Cardiovascular Section of American Physiological Society (FCVS), and a Trustee (elected) of Japanese Physiological Society (JPS). He is a member of the and the American Heart Association (AHA), International Society for Heart Research (ISHR), American Physiological Society (APS), Biophysical Society (BPS), and Cardiac Muscle Society, among others. His research interests include cardiac excitation-contarction/metabolism coupling, heart failure, sudden cardiac death, cardiac channelopathies, and cardiac mitochondrial biology. Come work with us! Visit https://med.umn.edu/lhi/about/jobs to see open positions in the O-Uchi lab.

Research Summary

Arrhythmia Heart Failure Adrenergic Signaling Ion Channels Mitochondria

Clinical Summary

Arrhythmia; Heart Failure

Bio

Areas of Interest

Cellular Physiology

Research Summary

Investigations in my laboratory focus on understanding mechanisms and regulation of electrolyte transport across epithelial tissues and on innate immune function of the airway epithelium in relation to cystic fibrosis, asthma and allergic airway disease. Cultured human airway epithelial cells are currently used to study regulation of ion transport and cell migration by a variety of signaling molecules. A combination of electrophysiological approaches and molecular techniques provide a means of identifying transport mechanisms and signaling pathways that are important in controlling salt and fluid movement across the airway epithelium. Studies of innate immune function are being conducted in collaboration with Dr. Hirohito Kita from the Mayo Clinic. These studies address the role of the airway epithelium in allergic inflammation induced by environmental allergens and fungal infection of the lung.

Publications

Refereed Articles

Srisomboon, Y., K. Iijima, M. Colwell, P.J. Maniak, Marissa Macchietto, C. Faulk, H. Kita, S.M. O’Grady, Allergen-induced DNA release by the airway epithelium amplifies type 2 immunity, J. Allergy Clin. Immunol. https://doi.org/10.1016/j.jaci.2022.09.034 (Oct 25, 2022) (IF = 14.29)

Srisomboon, Y., Ohkura, N., Iijima, K., Kobayashi, T., Maniak, P.J., Kita, H., O’Grady, S.M., Airway exposure to polyethyleneimine nanoparticles induces type 2 immunity by a mechanism involving oxidative stress and ATP release. International Journal of Molecular Sciences, 22 (16), 9071-9089, 2021.

Srisomboon Y, Squillace DL, Maniak PJ, Kita H, O'Grady SM. Fungal allergen-induced IL-33 secretion involves cholesterol-dependent, VDAC-1-mediated ATP release from the airway epithelium. J Physiol., 598 (10):1829-1845. 2020.

Editors’ Choice Award: The Journal of Physiology. This paper was highlighted in the Perspectives article by: Ahmad S and A. Ahmad. Treating fungus-induced allergic asthma: Do VDACs have the answer! J Physiol. 598 (10), 1799–1800, 2020.

Journal Cover: The editors of The Journal of Physiology chose Fig 5C from this paper as the cover image for volume 598 (10), 2020. 

Graeff R, Guedes A, Quintana R, Wendt-Hornickle E, Baldo C, Walseth T, O'Grady S, Kannan M. Novel Pathway of Adenosine Generation in the Lungs from NAD(+): Relevance to Allergic Airway Disease. Molecules, 25 (21), 1-18, 2020.

Refereed Articles on PubMed

Book Chapter

O’Grady, SM, Ion Transport: Potassium Channels, Encyclopedia of Respiratory Medicine, 2nd Edition, Volume 1, pp 669-677, 2021.

O’Grady, S.M. (Invited review) Ion Transport, Potassium Channels. Encyclopedia of Respiratory Medicine In Press. 2020.

O’Grady, S.M. 2017. CFTR involvement in cell migration and epithelial restitution. In: Progress in Understanding Cystic Fibrosis. D.D. Sriramulu, Ed., Rijeka: InTech; 2017, pp 1-22.

Bankers-Fulbright, J. and S.M. O'Grady. 2012. Mechanisms of eosinophil degranulation: pH Regulation and release of major basic protein. In: Eosinophils: Structure, Biological Properties and Role in Disease. NOVA Science Publishers, Hauppauge, NY.

Brown, D.R. and S.M. O'Grady. 2008. The Ussing chamber and measurement of drug actions on mucosal ion transport. In: Current Protocols in Pharmacology. John Wiley, NY, 41:7.12.1-7.12.17, 2008.

Abstracts

Collins, M., M. Imbrogno, E. Kramer, J. Brewington, N. Zhang, P. Sharon, E. Kopras, J Meeker, H. Morgan, A. Ostmann, S. O'Grady, B. Trapnell, J. Clancy, K. Hudock, Neutrophil extracellular traps disrupt bronchial epithelial barrier function: Alpha-1 antitrypsin to the rescue. J. Cystic Fibrosis, 21: S223, 2022

Iijima, K., T. Kobayashi, K. Ohara, K. Matsumoto, R. Tei, S. O'Grady, H. Kita, Allergen-induced extracellular release of self-DNA promotes innate type 2 immune responses in the lung, J. Allergy Clin Immunol., 149: AB75, 2022

Almutlaq, R., A. Dayton, J. Ross, Y. Srisomboon, S. O'Grady, L.C. Evans, Exposure to excess albumin causes inflammatory activation of the proximal tubule, Hypertension, 79: AP082, 2022.

Moore, P., Wiggen, T., Kent, L., Arif, S., Lucas, S., O’Grady, S.M. Hunter, R., Anaerobic microbiota facilitate Pseudomonas aeruginosa access to the airway epithelium in a novel co-culture model of colonization. Journal of Cystic Fibrosis, 20, S195, 2021.

Ohara, K., Iijima, K., O'Grady, S.M., Kita, H., Detergent induces active release of IL-33 from airway epithelial cells and promotes innate type 2 responses in the lungs. Journal of Allergy and Clinical Immunology 147 (2), AB38, 2021.

Srisomboon, Y,  Maniak PJ,  Kita H, O'Grady SM. K2P channel inhibition enhances allergen‐induced ATP release by a mechanism involving PKC activation in human bronchial epithelial cells. FASEB J. 34(S1): doi.org/10.1096/fasebj.2020.34.s1.05204.

Srisomboon Y, Maniak PJ, Squillace D, Kita H, O’Grady SM. Simvastatin Inhibits Allergen-induced IL-33 Secretion in Human Bronchial Epithelial Cells by Blocking ATP Release and Ca2+ Uptake. FASEB J 33: 734.5-734.5, 2019.

Presentations

O' Grady, S.M. Invited Seminar: City-wide Pulmonary Research Conference, Minneapolis MN, 06/25/2021. "Vital DNA Release by the Airway Epithelium and its role in Inflammation."

O' Grady, S.M. Invited Speaker (Zoom Presentation): Department of Biology, Virginia Commonwealth University, Richmond VA, 10/07/2020: “VDAC-1 mediated ATP release and type 2 immunity in airways”.

O' Grady, S.M. 2019. Epithelial ETosis and airway host-defense following fungal aeroallergen exposure. CVM Research Seminar, St. Paul, MN. March 6. 

O' Grady, S.M. 2018. Glucocorticoid regulation of airway epithelial ion transport during mucociliary differentiation. Department of Medicine, Minneapolis, MN. November 14.

Invited Reviews

Ingbar, D.H., M. Bhargara, and S.M. O'Grady. 2009. Mechanisms of alveolar epithelial chloride absorption. Am. J. Physiology [Lung Cell and Mol. Physiol.] 297: L813-L815.

Chanson, M., B.A. Kotsias, C. Peracchia, and S.M. O'Grady. 2007. Interaction of gap junction channels with other membrane channels and transporters. Prog. Biophys. Mol. Biol. 94:233-244.

O'Grady, S.M. 2006. Ion transport: Potassium channels. Encyclopedia of Respiratory Medicine 8:477-482.

Palmer, M.L., A.C. Fahrenkrug, and S.M. O'Grady. 2006. RNA interference and ion channel physiology. Cell Biochem. Biophys. 46:1-17.

O'Grady, S.M. and S.Y. Lee. 2005. Molecular diversity and function of voltage-gated (Kv) potassium channels in epithelial cells. Int. J. Biochem. Cell Biol. 37:1578-1594.

Lee, S.Y. and S.M. O'Grady. 2003. Modulation of ion channel function by P2Y receptors. Cell Biochem. Biophys. 39:75-88.

O'Grady, S.M. and S.Y. Lee. 2003. Chloride and potassium channels in alveolar epithelial cells. Am. J. Physiology (Lung Cell and Molecular Physiol.) 284:L689-L700.

O'Grady, S.M., X. Jiang, and D.H. Ingbar. 2000. CL channel activation is necessary for stimulation of amiloride-sensitive NA transport in cultured adult rat alveolar epithelial cells. Am. J. Physiol. [Lung Cell and Molecular Physiology] 278:L239-L244.

Honors and Awards

• Dec 2022: Editor’s Choice Recognition; Journal of Allergy and Clinical Immunology.
• Oct 2022: Star Reviewer Award; American Journal of Physiology [Cell Physiology].
• May 2020: Editor’s Choice Recognition; Journal of Physiology.
• Jul 2017: Editor's Choice Recognition; Journal of Physiology.
• Jun 2017: APSselect Award; American Physiological Society.
• Apr 2017: Paper of the Year Award; American Journal of Physiology [Cell Physiology].
• Aug 2016: APSselect Award; American Physiological Society.
• Apr 2012: Star Reviewer Award; American Journal of Physiology [Cell Physiology].
• Jul 2007: Teaching excellence in Veterinary Physiology Award, College of Veterinary Medicine, University of Minnesota.
• May 1990: Gordon L. Starr Outstanding Faculty Contribution Award, University of Minnesota.

Teaching Summary

ANSC/PHSL 5702; PHSL 4702: Cell Physiology

Editorial Service

Editorial Board and Topic Editor, International Journal of Molecular Sciences 

Editorial Advisory Board, American Journal of Physiology [Cell Physiology].

Editorial Advisory Board, International Archives of Clinical Pharmacology.

Bio

Dr. Osborn is interested role of the autonomic nervous system in long-term control of cardiovascular function and the pathogenesis of cardiometabolic diseases. The primary focus of his laboratory the role of renal nerves in the pathogenesis and maintenance of hypertension. This is motivated by clinical trials of targeted sympathetic ablation in humans using medical devices. Dr. Osborn’s laboratory is investigating the mechanisms of organ specific sympathetic nerve activity in the maintenance of neurogenic hypertension as a translational platform for development of novel antihypertensive therapies in the very near future. Dr. Osborn is Director Minnesota Center for Autonomic Neuromodulation which is leading a 7-center global study of the effects of vagal nerve modulation on physiological systems in human subjects.

Dr. Osborn’s research efforts are concentrated on therapies for the treatment of cardiovascular and metabolic diseases. He has made important contributions to our understanding the role of the sympathetic nervous system in the pathogenesis of hypertension. Dr. Osborn is also an internationally recognized expert in the development of autonomic neuromodulation therapies.

Research Summary

Research in my laboratory is directed towards gaining an integrative understanding of the role of the central nervous system in the long-term regulation of arterial pressure and the pathogenesis of hypertension. At the present time we are investigating how circulating hormones, such as angiotensin II and aldosterone, are monitored by specialized sites within the brain called circumventricular organs. We are investigating how these regions influence ongoing sympathetic nerve discharge and ultimately the regulation of arterial pressure. Our long-term goal is to understand, in a quantitative way, the role of such hormonal-sympathetic interactions in normal physiology and the pathophysiology of hypertension. Specifically, we are studying how such interactions are influenced by alterations in dietary salt in hopes of understanding the neurogenic basis of salt-dependent hypertension. A variety of experimental approaches are employed to address these issues including state-of-the-art long-term monitoring of cardiovascular hemodynamics and application of cellular/molecular neurobiological techniques. We have also initiated a collaborative project with the Department of Mathematics to begin developing new mathematical models of how the nervous system regulates cardiovascular function over long periods of time.

Bio

The Pacak laboratory investigates mechanisms that lead to mitochondrial dysfunction in a variety of disease settings using differentiated patient-derived induced pluripotent stem cells (iPSCs), mouse models, and adeno-associated virus (AAV) mediated gene delivery systems.

Research Summary

The Pacak laboratory is focused on identifying common mechanisms of disease related to mitochondrial function that can be augmented through gene therapies. The lab uses differentiated iPSCs and a variety of in vivo models to pursue these investigations.

Bio

Angela Panoskaltsis-Mortari, PhD is a Professor of Pediatrics in the Division of Blood and Marrow Transplant & Cellular Therapy. She is also a Professor of Medicine in the Division of Pulmonary, Allergy, Critical Care and Sleep. Dr. Panoskaltsis-Mortari is the Director of the Cytokine Reference Laboratory, the Director of the 3D Bioprinting Facility at the University of Minnesota and Vice Chair for Research for the Department of Pediatrics.
Dr. Panoskaltsis-Mortari received her PhD from the University of Western Ontario. She was a post-doctoral fellow in the Department of Pathology at the University of Alabama and a post-doctoral research associate in the Department of Pediatrics at the University of Minnesota. She joined the University of Minnesota faculty in 1995.
Dr. Panoskaltsis-Mortari has board certification from the American Board of Medical Laboratory Immunology. She is a member of numerous immunology, pulmonary, and hematology professional societies, and the author of over 275 articles which have appeared in such publications as Advanced Materials, Journal of Clinical Investigation, Blood, Biology of Blood and Marrow Transplantation, and American Journal of Physiology (Lung, Cell. & Mol. Physiol.).

Research Summary

With 25 years of experience in animal models of stem cell transplant, lung injury, mesenchymal stem/stromal cell therapy and the biology of graft-vs-host disease (GVHD) after bone marrow transplant, Dr. Angela Panoskaltsis-Mortari's work has evolved into the bioengineering field, and she is recognized as one of the thought leaders in lung bioengineering. Dr. Panoskaltsis-Mortari's laboratory research currently focuses upon 2 major themes: 1) bioengineering autologous tissues such as trachea and esophagus using 3D bioprinting and customized hydrogels including decellularized extracellular matrix; and 2) 3D bioprinting of cancer models.
Dr. Panoskaltsis-Mortari established and directs the 3D Bioprinting Facility at the University of Minnesota. She also directs the UMN Cytokine Reference Laboratory (a CLIA-licensed facility). She is a member of the Stem Cell Institute, the Institute for Engineering in Medicine, the Lillehei Heart Institute, the Masonic Cancer Center, the Center for Immunology, and the Robotics Institute. She is funded by the NIH, has mentored many post-docs, MD trainees, graduate students and undergrads in various training programs. Her goal is to realize the potential of regenerative medicine by converging the fields of stem cell biology, mechanical & biomedical engineering, biomaterials, physiology, robotics, and surgery to bioengineer autologous tissues/organs for transplant using a patient's own cells that would not be rejected by their immune system.

Bio

Our laboratory has a long-term interest in understanding the molecular mechanisms controlling lineage-specific differentiation of pluripotent stem cells (PSC), which has led to the efficient generation of  PSC-derived myogenic progenitor cells endowed with in vivo regenerative potential. Current research projects focus on the effect of the environment on the engraftment and maturation of PSC-derived myogenic progenitors, the development of allogeneic and autologous cell therapy for muscular dystrophies (MD), and application of MD patient-specific iPSC-derived muscle derivatives for disease modeling and drug discovery.

Creative Activity Summary

Full list of publications at Experts@Minnesota or PubMed.

1. Baik J, Ortiz-Cordero C, Magli A, Azzag K, Crist SB, Yamashita A, Kiley J, Selvaraj S, Mondragon-Gonzalez R. Perrin E, Maufort JP, Janecek JL, Lee RM, Stone LH, Rangarajan P, Ramachandran S, Graham ML, & Perlingeiro RCR. (2023). Establishment of skeletal myogenic progenitors from non-human primate induced pluripotent stem cells. Cells, 12(8), 1147; https://doi.org/10.3390/cells12081147.
2. Singh BN, Yucel D, Garay BI, Tolkacheva EG, Kyba M, Perlingeiro RCR, van Berlo J, & Ogle BM, (2023) Proliferation and Maturation: Janus and the art of engineered cardiac tissue. Circulation Research, 132(4):519-540.  PMCID: PMC9943541.
3. McKenna DH & Perlingeiro RCR, (2023) Development of allogeneic iPS cell-based therapy: from bench to bedside. EMBO Molecular Medicine, 15(2):e15315. PMCID: PMC9906386.
4. Azzag K, Bosnakovski D, Tungtur S, Salama P, Kyba M, & Perlingeiro RCR, (2022) Transplantation of pluripotent stem cell-derived myogenic progenitors counteracts disease phenotypes in a mouse model of FSHD. NPG Regenerative Medicine,  7(1):43. PMCID: PMC9440030.
5. Garay BI, Givens S, Stanis N, Magli A, Yücel D, Abrahante JE, Goloviznina NA, Soliman HAN, Dhoke NR, Baik J, Kyba M, van Berlo JH, Ogle B, & Perlingeiro RCR, (2022) Inhibition of mitogen-activated protein kinase pathway enhances maturation of human iPSC-derived cardiomyocytes. Stem Cell Reports. 17(9):2005-2022. PMCID: PMC9481895.
6. Kim H, & Perlingeiro RCR, (2022) Generation of human myogenic progenitors from pluripotent stem cells for in vivo regeneration. Cellular and Molecular Life Sciences. 8;79(8):406. doi: 10.1007/s00018-022-04434-8. PMCID: PMC9270264.
7. Ortiz-Cordero C, Bincoletto, C, Dhoke N, Selvaraj S, Magli A, Zhou H, Kim D-H, Bang AG, & Perlingeiro RCR, (2021), Defective autophagy and increased apoptosis contribute toward the pathogenesis of FKRP-associated muscular dystrophies. Stem Cell Reports. 16(11):2752-2767. PMCID: PMC8581053.
8. Dhoke N, Kim H, Selvaraj S, Oliveira NAJ, Azzag K, Tungtur S, Ortiz-Cordero C, Kiley J, Lu QL, Bang A, & Perlingeiro RCR, (2021), A universal gene correction approach for FKRP-associated dystroglycanopathies to enable autologous cell therapy. Cell Reports. 36(2):109360. PMCID: PMC8327854.
9. Ortiz-Cordero C, Magli A, Dhoke N, Kuebler T, Selvaraj S, Oliveira NA, Zhou H, Sham YY, Bang AG, & Perlingeiro RCR, (2021), “NAD+ enhances ribitol and ribose rescue of α-dystroglycan functional glycosylation in human FKRP-mutant myotubes”. Elife, 2021 10:e65443. PMCID: PMC7924940
10. Ortiz-Cordero C, Azzag K, & Perlingeiro RCR, (2021), “Fukutin-Related Protein: from Pathology to Treatments”. Trends in Cell Biology, 31:197-210. PMID: 33272829 (cover article).
11. Kim H, Selvaraj S, Kiley J, Azzag K, Garay BI, & Perlingeiro RCR, (2021), “Genomic safe harbor expression of PAX7 for the generation of engraftable myogenic progenitors”. Stem Cell Reports, 16:10-19.PMCID: PMC7815936
12. Baik J, Felices M, Yingst A, Theuer, CP, Verneris MR, Miller JS, & Perlingeiro RCR,(2020), “Therapeutic effect of TRC105 and decitabine combination in AML xenografts”. Heliyon, 6(10):e05242. PMCID: PMC7566100.
13. Incitti T, Magli A, Jenkins J, Lin K, Yamamoto A and Perlingeiro RCR, (2020), “Pluripotent stem cell-derived skeletal muscle fibers preferentially express oxidative myosin heavy-chain isoforms: new implications for Duchenne Muscular Dystrophy”. Skeletal Muscle, 10(1):17. PMCID: PMC7268645
14. Azzag K, Ortiz-Cordero C, Oliveira NAJ, Magli A, Selvaraj S, Tungtur S, Upchurch W, Iaizzo PA, Lu QL and Perlingeiro RCR, (2020) “Efficient Engraftment of Pluripotent Stem Cell-Derived Myogenic Progenitors in a Novel Immunodeficient Mouse Model of Limb Girdle Muscular Dystrophy 2I”. Skeletal Muscle, 10(1):10. PMCID: PMC7175515.
15. Selvaraj S, Mondragon-Gonzalez R, Xu B, Magli A, Kim H, Lainé J, Kiley J, McKee H, Rinaldi F, Aho J, Tabti N, Shen W, & Perlingeiro RCR, (2019) “Screening identifies small molecules that enhance the maturation of human pluripotent stem cell-derived myotubes”. eLIFE, 8. pii: e47970. PMCID: PMC6845233.
16. Selvaraj S, Dhoke N, Kiley J, Aierdi AJM, Mondragon-Gonzalez R, Killeen G, Oliveira VKP, Tungtur S, Munain AL & Perlingeiro RCR, (2019) “Gene Correction of Limb Girdle Muscular Dystrophy Type 2A Patient-Specific iPS Cells for the Development of Targeted Autologous Cell Therapy”. Molecular Therapy,27:2147-2157. PMCID: PMC6904833.
17. Selvaraj S, Kyba M & Perlingeiro RCR, (2019) “Pluripotent Stem Cell-Based Therapeutics for Muscular Dystrophies” Trends in Molecular Medicine. 25:803-816. PMCID: PMC6721995. (cover article)
18. Mondragon-Gonzalez R, Azzag K, Selvaraj S, Yamamoto A & Perlingeiro RCR, (2019) “Transplantation studies reveal internuclear transfer of toxic RNA in engrafted muscles of myotonic dystrophy 1 mice”. eBioMedicine. 47:553-562. PMCID: PMC6796515.
19. Magli A, Baik J, Pota P, Ortiz Cordero C, Kwak IY, Garry DJ, Love PE, Dynlacht BD and Perlingeiro RCR, (2019) “Pax3 cooperates with Ldb1 to direct local chromosome architecture during myogenic lineage specification”. Nature Communications, 10:2316. PMCID: PMC6534668.

Full list of publications at Experts@Minnesota or PubMed.

Bio

Administrator Info
Name: Lisa Moe
Phone:
Email: seif0046@umn.edu
Fax: 
Mail: Cancer & Cardiovascular Research Building
Lillehei Heart Institute
1st Floor Mailroom CCRB
2231 6th Street SE
Minneapolis, MN 55455

Summary
Dr. Prins is dedicated to understanding right ventricular (RV) dysfunction in pulmonary hypertension. He studies the RV in clinical studies as well as his basic science laboratory. He has given talks at multiple international conferences and receives grant funding from the NIH. Come work with us! Visit https://med.umn.edu/lhi/about/jobs to see open positions in the Prins lab.

Research Summary

• Pulmonary Hypertension
• Right Ventricular Failure
• CTEPH
• Clinical Trial Participation
• Pulmonary Balloon Angioplasty

Teaching Summary

• Cardiac Physiology

Clinical Summary

CTEPH, Invasive hemodynamics, Pulmonary embolus, Pulmonary artery hypertension, Pulmonary hypertension and right heart failure, Right ventricular dysfunction

Bio

Dr. Revelo is an Associate Professor in the Department of Integrative Biology & Physiology and Center for Immunology. He has a broad background in physiology, immunology, and metabolism and expertise in inflammation during cardio-metabolic disease. His research explores the role of the immune system and inflammation in the pathophysiology of obesity-related diseases such as fatty liver disease and heart failure.

Research Summary

Dr. Revelo's research program focuses on the following areas:
1. Mechanisms of hepatic and intestinal inflammation in fatty liver disease and cancer.
2. Immune mechanisms of cardiac remodeling during heart failure
3. Anti-inflammatory mechanisms of exercise training and bariatric surgery

Bio

Research in our lab is focused in understanding the mechanisms that control the genome organization and function during development, as well as their alterations in human diseases. We are exploiting differentiation protocols of induced pluripotent stem cells (iPSCs) derived from patients to model disease progression and genomic technologies to characterize nuclear organization

Research Summary

The pathways important for driving autoimmune and inflammatory diseases as well as age related degeneration are surprisingly similar. For example, inhibition of the transcription factor NF-?B is therapeutic in mouse models of autoimmunity and inflammation as well as Duchenne muscular dystrophy and aging. Similarly, inhibition of IL-1ß signaling by gene transfer of the IL-1 receptor antagonist protein is therapeutic in multiple models of diseases. The Robbins laboratory is developing novel approaches to treat autoimmune (type 1 diabetes, rheumatoid arthritis), inflammatory (inflammatory bowel disease, delayed type hypersensitivity) and age-related degenerative diseases using biologics and small molecules. The therapeutic approaches being developed include: 1) AAV mediated gene transfer of anti-inflammatory or immunosuppressive agents; 2) Peptide and small molecule inhibitors of the transcription factor of NF-?B; 3) Novel osteogenic peptides; 4) Adult stem cells; 5) Microvesicles (exosomes) derived from immunoregulatory or stem cells able to block inflammation or promote regeneration; and 6) Identification of drugs able to reverse cellular senescence for improving healthy aging. Although the majority of the studies are being performed in mouse models of disease, approaches to treat osteoarthritis by intra-articular AAV-mediated gene transfer and Duchenne muscular dystrophy by systemic treatment with a NF-?B inhibitory peptide will soon be entering the clinic.

Bio

Dr. Ruan received his Ph.D. in Genetics from Nanjing University in 2008. He then did his postdoctoral training at Yale University School of Medicine from 2009 to 2015. In January 2016, he started his independent research lab at the Department of Integrative Biology & Physiology of University of Minnesota Medical School.

Research Summary

The research in my laboratory is directed towards understanding how environmental cues and intrinsic signals are integrated to regulate metabolic processes in health and disease. The Ruan laboratory currently conducts an integrated program in the following directions on tissue adaptation and remodeling upon metabolic stress: (1) protein O-GlcNAcylation in physiology and disease, (2) adipose Biology remodeling and energy balance, (3) intestinal epithelium at the interface between gut microbes and host physiology, and (4) immune homeostasis and its regulation of systemic metabolism. Using an integrative approach, we aim to define the pathological alterations of metabolic communication in diseases including obesity, diabetes, inflammation, and aging. Ultimately, we hope to identify targets and to design therapeutics for these diseases.

Bio

Dr. Elizabeth Seaquist is the Nesbitt Chair and Head of the Department of Medicine. Awards recognizing her research and mentoring include the American Diabetes Association’s Transformative Woman in Diabetes Award in 2019 and the Albert Renold Award for Mentoring in 2020. She served as the President for Medicine and Science of the American Diabetes Association in 2014. As a clinical investigator, Dr. Seaquist is interested in hypoglycemia and the complications of diabetes. Her research focuses on the effect of diabetes on brain metabolism, structure, and function. She was the site investigator for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) study, and the Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) study. She has an active clinical practice and is board certified in Internal Medicine and Endocrinology, Diabetes, and Metabolism.

Research Summary

• Impact of diabetes on cerebral structure and function
• Hypoglycemia in diabetes

Clinical Trials

• Cerebral Responses to Insulin-Induced Hypoglycemia
• Effect of Recurrent Hypoglycemia

Clinical Summary

• Management of type 1 and type 2 diabetes
• Complications of diabetes
• Hypoglycemia in diabetes

Research Summary

My laboratory focus on the development of consistent and accurate computational models to understand the fundamental forces that governs the biomolecular recognition process. These models serves as the platform for understanding binding selectivity and structure-based drug discovery. We work collaboratively with researchers across the University to develop novel cardiovascular, antiviral, antibacterial and anticancer therapies.

Bio

Administrator Info
Name: GI Division
Phone: 612-625-8999
Email: gidivision@umn.edu
Mail: 420 Delaware Street SE, MMC 36, Minneapolis, MN 55455

Summary
Dr. Steer accepted a Hepatology Fellowship at the NIH in the Section on Diseases of the Liver in 1976 and remained on staff at the NIH as an Expert in his field for an additional 10 years. In 1989, Dr. Steer returned to the University of Minnesota as a Professor in the Departments of Medicine, and Genetics, Cell Biology and Development. During his time at the University, Dr. Steer has been active in mentorship of PhD students and post-doctoral fellows in his lab, is a member of multiple committees and has continued to be academically productive in his current area of research, which is regenerative medicine.

Research Summary

The Sleeping Beauty (SB) transposon system in non-viral gene therapy Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, as an anti-apoptotic agent Role of microRNAs in gene regulation for different target organs and stem cell populations Basic and translational applications to human disease Regenerative medicine using gene editing (CRISPR) and blastocyst complementation Steer's laboratory has been involved in three major areas of research during the last five years. The Sleeping Beauty (SB) transposon system functions via a cut-and-paste mechanism catalyzed by the binding of SB transposase to inverted repeats/direct repeats (IR/DRs) of the mariner transposon. It excises the relevant transgene from the transposon at the IR/DRs and inserts the element into random TA dinucleotide sites within the genome. They are applying SB as a gene therapy vector to a variety of different animal disease models, including liver, bone marrow and brain disorders. Steer's laboratory is also interested in characterizing the effects of SB transposition on genomic methylation and histone acetylation.The second major area of research involves the use of ursodeoxycholic acid (UDCA), a hydrophilic bile acid, as a potent antiapoptotic agent. They have used UDCA as a therapeutic agent to treat transgenic models of Huntington's disease and retinitis pigmentosa as well as acute stroke, spinal cord injury, myocardial infarction, and acute renal failure. Steer's laboratory continues to study basic mechanisms and translational applications of UDCA. Of note, the South Korean FDA has recently approved its use for the treatment of ALS.Steer's lab is actively characterizing the role of microRNAs in gene regulation for a number of different target organs and stem cell populations. In particular, they have identified specific microRNAs that may be involved in the progression of colon from polyp to cancer; as well as their role in the regenerating liver. The studies are both basic and translational in nature. They are also identifying specific microRNAs as biomarkers of disease that can be assayed in blood. Most notably, they have recently discovered a unique nuclear profile of mature microRNAs; and a subset of microRNAs in mitochondria that may act as a rheostat for the control of apoptosis.Over the past seven years, Steer's lab has also focused on regenerative medicine, and research to create human livers in pigs for transplantation. The approach utilizes a combination of gene editing and a technology referred to as blastocyst complementation. This involves the knockout (KO) of specific developmental genes in the blastocyst of the pig; and the intra-blastocyst injection of pluripotent stem cells from the human donor to generate offspring that carry organs/cell types derived from that donor. The ultimate goal is to create human livers in pigs that are immunology identical to the recipient, thereby not requiring the use of immunosuppression…a paradigm shift in organ transplantation.

Bio

The Thomas Lab studies fundamental molecular motions and interactions that are responsible for cellular movement, to determine the molecular bases of muscle disorders, and to devise novel therapies based on these discoveries

Research Summary

Molecular dynamics of energy transduction in muscle health and disease, using site-directed spectroscopic probes Our goal is to understand the fundamental molecular motions and interactions that are responsible for cellular movement, to determine the molecular bases of muscle disorders, and to devise novel therapies based on these discoveries. We approach this multidisciplinary problem with a wide range of techniques -- physiology, enzyme kinetics, molecular genetics, peptide synthesis, computer simulation -- but our forte is site-directed spectroscopic probes. After attaching probes (spin labels, fluorescent dyes, phosphorescent dyes, or isotopes) to selected muscle proteins in solution or in cells , we perform magnetic resonance or optical spectroscopy to directly detect the motions of the force-generating proteins, actin and myosin, or the membrane ion pumps and channels responsible for muscle excitation and relaxation. These same tools are then used to test the efficacy of gene or drug therapies designed to treat heart failure or muscular dystrophy. Our research involves several types of muscle, but the laboratory focuses increasingly on the heart. Indeed, our newest and most exciting direction is to use the principles of structural biophysics to design new molecular therapies for heart failure. This is an extremely ambitious and high-risk goal, but we are in a unique position to achieve it, due to an unparalleled combination of technologies, insights, and expert collaborators. As a result of these advances, we have started a company, Photonic Pharma LLC ( http://www.photonicpharma.com/ ),with the goal of commercializing our discoveries in the field of drug discovery. 1 min video.

Research Summary

My laboratory utilizes an integrative approach to study the pathophysiological mechanisms of heart failure, with a specific focus on dystrophic cardiomyopathies. Patients with many forms of muscular dystrophy also have significant cardiac disease. Interestingly, several of the proteins associated with these dystrophic cardiomyopathies have also been implicated in heart failure resulting from more common causes (i.e., ischemic heart disease). Duchenne muscular dystrophy, the most common form of muscular dystrophy, is caused by mutations in the protein dystrophin. Dystrophin is a large protein that spans from the intracellular cytoskeletal actin lattice to a complex of glycoproteins in the sarcolemmal membrane, which in turn binds to the extracellular matrix. It functions both as a mechanical shock absorber and scaffold for a large array of signaling molecules. We study heart disease at varying levels of biological complexity including intact animals, isolated organs, and indivdual adult cardiomyocytes to obtain insights into disease mechanisms. We also probe molecular physiology, utilizing biochemical methodologies, transgenesis, and in vivo gene transfer. This highly integrated approach provides unique insights into the pathophysiology of heart disease and ultimately will enable us to develop novel therapeutic approaches.

Bio

Phu Tran is an Associate Professor in the Department of Pediatrics. His research focuses on mechanisms (molecular and epigenetic) underlying the long-term effects of early-life adversity on neural development. His lab has been investigating how early-life (fetal and early postnatal) environmental exposures (nutritional deficiency, opioids) result in long-term neural gene dysregulation associated with altered epigenetic signatures. His lab employs cutting-edge technology (ATACseq/ChIPseq/Single-cell sequencing/exosomes) to probe these changes in cord blood stem cells and rodent hippocampal cells with an ultimate goal to establish non-invasive biomarkers for brain development and health. His other research interests include molecular mechanisms regulating post-operative pain, neonatal hypoxic-ischemic brain injury, and nicotinic acetylcholine receptor chaperones.

Research Summary

Our research activities focus on two major goals. First, we investigate the long-term effects of early-life iron deficiency on hippocampal function. Iron deficiency is a major global health concern that affects conservatively 2 billion individuals worldwide, including about 30% of pregnant women and pre-school age children.It is well established that early-life iron deficiency has long lasting negative effects on cognition and socio-emotional behaviors in humans despite prompt iron treatment following diagnosis.These long-term effects constitute a significant cost to society in terms of educational attainment, job potential, and mental health.Thus, understanding at the cellular and molecular level how early iron deficiency affects brain development in animal models may lead to important insights into alternative therapeutic development to prevent and treat at risk pregnancies and children with iron deficiency. Second, we investigate the biological role of TMEM35A (NACHO) in the nervous system. TMEM35A has been shown to function as a chaperone for neuronal nicotinic acetylcholine receptors, which have been implicated in neuropathologies and psychopathologies (e.g., addiction, pain, Autism, Alzheimer, and schizophrenia). Defining the precise molecular function of this novel chaperone using a gene knockout mouse model and drug treatment is promising in defining new mechanisms and pathways that regulate cognition, pain, and addictive behaviors.The work may lead to new strategies to improving quality of life and productivity.

Bio

Administrator Info
Name: Mayna Xiong
Email: xion2253@umn.edu
Mail: Lillehei Heart Institute
2231 6th Street SE
1st-floor Mailroom CCRB
Minneapolis, Minnesota 55455

Summary
After obtaining his M.D. and Ph.D. degrees from the University of Maastricht, the Netherlands, Dr. Jop van Berlo performed postdoctoral research with Dr.Jeffery Molkentin at the Howard Hughes Medical Institute, Cincinnati Children's Hospital Medical Center. Upon joining the University of Minnesota he has built a research program focused on the cellular and molecular mechanisms of cardiac remodeling and regeneration. An active area of research is on the role of the immune system in orchestrating cardiac remodeling. Separately, the laboratory is interested in discovering regulators of cardiomyocyte proliferation.

Research Summary

My laboratory studies the cellular and molecular mechanisms of cardiac remodeling and regeneration. The goal of this research is to develop innovative strategies to enhance the limited ability of the heart to regenerate and stimulate reverse remodeling. To identify these strategies, we study the underlying mechanisms of endogenous remodeling and regeneration in mice. We are currently interested in discovering novel regulators of cardiomyocyte proliferation. We have candidate regulators that we are verifying in cell culture and in genetic mouse models. Furthermore, we are interested in the role of the immune system in orchestrating remodeling and regeneration.

Bio

Dr. Wendt has a long-standing interest in clinical and translational research in COPD, specifically focusing on biomarkers and pathways of disease. Dr. Wendt has participated on five large NIH COPD trials, three of which are ongoing and are a resource for developing trainees and junior faculty interested in clinical research. In addition, Dr. Wendt was recently the PI of a FAMRI award for a clinical trial related to the microbiome. This study provided a platform for a junior faculty (CDA awardee) to gain experience in clinical trials and to participate in the expansion to a multi-center trial. Dr. Wendt's current translational work has focuses on biomarkers and causal pathways in COPD leading to lung cancer (VA Lung Precision Oncology Program) and HIV associated COPD (NIH R01). These translational projects combine multiple investigators with expertise in genomics, transcriptomics, proteomics, computational and systems biology. Dr. Wendt also participates in a VA Cooperative Study (SHADE) to determine the respiratory effects of particulate matter in deployed Veterans and has a VA Collaborative Merit Award to phenotype exposure related pulmonary disease in the SHADE cohort. Through all this work Dr. Wendt has fostered cross-discipline collaborations, creating mentoring and collaborative opportunities for trainees and junior faculty. Dr. Wendt has and continues to accumulate a substantial and successful mentoring record. Dr. Wendt has mentored 5 graduate students,11 fellows, 3 PhD post-doctoral fellows and 5 faculty. Most notably are Dr. Alexa Pragman, recipient of VA CDA and recent VA Merit Award (microbiome in COPD), Dr. Theresa Laguna, recipient of NIH R01 (microbiome in CF infants) and recently recruited as Division Director of Pulmonary, Northwestern University, Dr. Maneesh Bhargava, recipient of CTSI K award and NIH R01, Dr. Arianne Baldomero, recipient of CTSI KL2 Award, Dr. Dwight Stoll, Professor and Co-Chair of Chemistry at Gustavus University and Dr. Filippo Colleti, Aerospace Engineering, recipient of NIH R22 (structure-function in COPD) and promoted to Associate Professor with tenure. Dr. Wendt also has extensive involvement with the American Thoracic Society (ATS) including chairing multiple assembly committees, which is a resource for networking and involvement for trainees and junior faculty.

Research Summary

Dr. Wendt’s research has focused on both clinical and translational research in COPD and associated contributors including tobacco, HIV, air pollution and COPD as a causal pathway to lung cancer. Dr. Wendt has participated on five large NIH COPD trials, including the NIH COPD Clinical Research Network and COPDGene. A significant area of focus includes identifying biomarkers and pathways of disease, particularly in lung cancer and HIV associated COPD. This translational program combines multiple investigators with expertise in genomics, transcriptomics, proteomics, computational and systems biology. Much of this work has included applying mass spectrometry techniques to measure proteins and metabolites in bronchoalveolar lavage fluid (BALF). This includes the development of a robust protocol to perform mass spectrometry, high throughput proteomics on small volumes of BALF. This workflow is highlighted in a recent publication and part of Dr. Wendt’s participation in an ATS document on BALF. Using this robust technique has led to new discoveries in proteomic and metabolic pathways in HIV-associated COPD and the role of complicated protease networks. 

Dr. Wendt’s interest in air pollution and chronic lung disease dates to her participation as a delegate for the University of Minnesota and Chinese Academy of Science to address the health effects of air pollution in China. This resulted in two publications on the effects of air pollution exposure on lung disease and biomarkers of lung disease. Following this she became a Site PI for the VA Cooperative Study #595 Service and Health Among Deployed Veterans (SHADE). SHADE is an epidemiology study to determine the effects of deployment-related air pollution exposure, including burn pits, on lung function and symptoms. This study uses sophisticated modeling to identify individual air pollution exposure to correlate to lung function and symptoms. To further characterize this population, Dr. Wendt was awarded a VA Merit Award as part of a Cooperative Merit Award to characterize biomarkers of airway injury and inflammation in a subset of SHADE participants with respiratory symptoms. These biomarkers in combination with assessment of anatomical and structural changes on chest computed tomography and airway physiology in the same Veteran population will allow detailed characterization of respiratory endotypes related to PM2.5 exposure. In addition, using the VA Corporate Data Warehouse (CDW) we have identified over 1.2 million Veterans with COPD and using this unique cohort is in collaboration with Dr. Berman, Environmental Sciences, to determine the association of air pollution and mortality in a vulnerable population.

Clinical Summary

Clinical Interests COPD; Critical Care Clinic Focus My major clinical focus has been on advanced therapies for emphysema. I am the Co-Director of the Lung Volume Reduction Surgery Program and I am currently participating on the NIH COPD Clinical Research Network. The University of Minnesota has been designated the clinical coordinating center for this network.

Research Summary

My lab is interested in understanding the contribution of myeloid cells in the pathogenesis of metabolic and cardiovascular diseases, like atherosclerosis. We aim to determine mechanisms regulating the development and function of tissue-resident macrophages, as well as fate-decisions of circulating monocytes upon entry into inflamed tissues.

Bio

Administrator Info
Name: Kathy Vang
Email: vang3630@umn.edu
Mail: 420 Delaware Street SE
MMC 508 Mayo
8508A (Campus Delivery Code)
Minneapolis, MN 55455

Summary
Born in London, UK, Dr. Yannopoulos received his M.D. from the University of Athens in Greece. He completed his medicine residency and general-cardiology fellowship at the University of Minnesota. Following an interventional-cardiology fellowship at Johns Hopkins University in Baltimore, Maryland, Dr. Yannopoulos joined the University of Minnesota faculty in 2008. In March 2010, he became the research director for interventional cardiology.Dr. Yannopoulos is board-certified in internal medicine, cardiology, and interventional cardiology. His clinical interests include emergent cardiac care, coronary-artery disease, and congenital and peripheral intervention.Dr. Yannopoulos's research involves cardiopulmonary resuscitation, hypothermia, and myocardial salvage during acute coronary syndromes. He is considered an authority in cardiorespiratory interactions and hypothermia during CPR. His work in the laboratories of Dr. Keith Lurie (at the University of Minnesota) and Dr. Henry Halperin (at Johns Hopkins University) has helped change current CPR practices.Dr. Yannopoulos is a member of the American Heart Association's CPR guidelines-writing committee, and of the basic life support and research working-group subcommittees. He also serves on the organization committee for the AHA's Resuscitation Science Symposium (ReSS), the largest international conference addressing CPR and emergent cardiac/trauma care.Dr. Yannopoulos is the recipient of two American Heart Association Young Investigator awards (2005 and 2008), and has received AHA and NIH grant support for his work in CPR devices designed to improve bloodflow and clinical outcomes.

Clinical Summary

• Coronary artery disease and intervention
• CPR
• Interventional cardiology
• Peripheral vascular disease
• Resuscitation
• Structural heart disease