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

Bryce A. Binstadt, MD, PhD, is an Associate 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

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

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

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.

Executive Assistant:

Sally Sawyer
Administrative Phone: 612-624-6666 (then hit 4 for the Academic Office)
Administrative Email: sallyann@umn.edu
Administrative Fax Number: 612-624-0644

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.

• View Experts@Minnesota profile
• View PubMed article list
• Visit Walter Low Laboratory

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, 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

2020:

Arpke, R.W., B.C. Collins, N. Lu, D.A. Lowe, and M. Kyba. Assessment of satellite cell self-renewal reveals minimal decline with aging but strong evidence for competition within the stem cell compartment. Aging Cell. In Press, April 2020.

Bosnakovski, D., A.S. Shams, C. Yuan, M.T. da Silva, E.T. Ener, C.W. Baumann, A.J. Lindsay, M. Verma, A. Asakura, D.A. Lowe, and M. Kyba. Transcriptional and cytopathological hallmarks of FSHD in chronic DUX4-expressing mice. J. Clin. Invest. 2020. https://doi.org/10.1172/JCI133303.

Lindsay, A., C.W. Baumann, R.T. Rebbeck, S.L. Yuen, W.M. Southern, J.S. Hodges, R.L. Cornea, D.D. Thomas, J.M. Ervasti, and D.A. Lowe. Mechanical factors tune the sensitivity of mdx muscle to eccentric strength loss and its protection by antioxidant and calcium modulators. Skelet. Muscle 10:3, 2020. PMID 32007101. PMC6995146.

Baumann, C.W., G.L. Warren, and D.A. Lowe. Plasmalemma function is rapidly restored in mdx muscle after eccentric contractions. Med. Sci. Sport Exerc.52: 354-361, 2020. PMID 31415447. PMC6962540.

2019:

Iñigo, M.R., A.J. Amorese, M.D. Tarpey, N.P. Balestrieri, K.G. Jones, D.J. Patteson, K.C. Jackson, M.J. Torres, C.T. Lin, C.D. Smith, T.D. Heden, S.L. McMillin, L.A. Weyrauch, E.C. Stanley, C.A Schmidt, B.B. Kilburg-Basnyat, S.W. Reece, C.E. Psaltis, L.A. Leinwand, K. Funai, J.M. McClung, K.M. Gowdy, C.A. Witczak, D.A. Lowe, P.D. Neufer, and E.E. Spangenburg. Estrogen receptor-? in female skeletal muscle is not required for regulation of muscle insulin sensitivity and mitochondrial regulation. Mol. Metab. 34: 1-15, 2019. PMID 32180550. PMC6994285.

Collins, B.C., R.W. Arpke, A.A. Larson, C.W. Baumann, N. Xie, C.A. Cabelka, N.L. Nash, H.K. Juppi, E.K. Laakkonen, S. Sipilä, V. Kovanen, E.E. Spangenburg, M. Kyba, and D.A. Lowe. Estrogen regulates the satellite cell compartment in females. Cell Reports 29: 368-381, 2019. PMID 31291574. PMC6655560.

Collins, B.C., E.K. Laakkonen, and D.A. Lowe. Aging of the musculoskeletal system: How the loss of estrogen impacts muscle strength. BONE Special Issue: Musculoskeletal Aging123: 137-144, 2019. PMID 30930293. PMC6491229.

Rajaganapathy, S., J. McCourt, S. Ghosal, A.Lindsay, P.McCourt, D.A. Lowe, J.M. Ervasti, and M. Salapaka. Distinct mechanical properties in homologous spectrin-like repeats of utrophin. Scientific Reports 9(1): 5210, 2019. PMID 30914715. PMC6435810.

Lindsay, A., W.M. Southern, P. McCourt, A. Larson, J. Hodges, D.A. Lowe, and J.M. Ervasti. Variable cytoplasmic actin expression impacts the sensitivity of different dystrophin-deficient mdx skeletal muscles to eccentric contraction. FEBS J. 286: 2562-2576, 2019. PMID 30942954. PMC6613979.

Lindsay, A., A. Larson, M. Verma, J.M. Ervasti, and D.A. Lowe. Isometric resistance training increases strength and alters histopathology of dystrophin-deficient mouse skeletal muscle. J. Appl. Physiol.126:363-375, 2019. PMID 30571283. PMC6397410.

Cabelka, C.A., C.W. Baumann, B.C. Collins, N. Nash, G. Le, A. Lindsay, E.E. Spangenburg, and D.A. Lowe. Effects of ovarian hormones and estrogen receptor ? on physical activity and skeletal muscle fatigue in female mice. Exp. Gerontol. 115:155-164, 2019. PMID 30415069. PMC6331238.

Lindsay, A., C.M. Chamberlain, B. Witthelm, D.A. Lowe, and J.M. Ervasti. Dystrophinopathy-associated dysfunction of Krebs cycle metabolism. Hum. Mol. Genet. 28:942-951, 2019. PMID 30476171. PMC6400043.

2018:

Nelson, D.M., A. Lindsay, L.M. Judge, K. Duan, J.S. Chamberlain, D.A. Lowe, and J.M. Ervasti. Variable rescue of microtubule and physiological phenotypes in mdx muscle expressing different miniaturized dystrophins. Hum. Mol. Genet. 27:2090-2100, 2018. PMID 29901725. PMC6049009.

Lindsay, A., McCourt, P., P. Karachunski, D.A. Lowe, and J.M. Ervasti. Xanthine oxidase is hyper-active in Duchenne muscular dystrophy. Free Rad. Biol. Med. 129:364-371, 2018. PMID 30312761. PMC6269445.

Olthoff, J.T., A. Lindsay, R. Abo-Zahrah, K.A. Baltgalvis, X. Patrinostro, J.J. Belanto, D. Yu, B.J. Perrin, D.J. Garry, G.G. Rodney, D.A. Lowe, and J.M. Ervasti. Loss of peroxiredoxin-2 exacerbates ROS-mediated force loss in dystrophin-deficient muscle. Nat. Commun. 30;9(1):5104, 2018. PMID 30504831. PMC6269445.

Levy, Y., J.A. Ross, M. Niglas, V.A. Snetkov, S. Lynham, C. Liao, M.J. Puckelwartz, Y. Hsu, E.M. McNally, M. Alsheimer, S.D.R. Harridge, S.G. Young, L.G. Fong, Y. Español, C. Lopez-Otin, B.K. Kennedy, D.A. Lowe, and J. Ochala. Prelamin A causes aberrant myonuclear arrangement and results in muscle fiber weakness. J. Clin. Invest. Insight 3(19): e120920, 2018. PMID30282816. PMC6237469.

Phung, L.A., S.M. Karvinen, B.A. Colson, D.D. Thomas, and D.A. Lowe. Age affects myosin relaxation states in skeletal muscle fibers of female but not male mice. PLoS ONE 13(9): e0199062, 2018. PMID 30226869. PMC6143227

Le, G., S.A. Novotny, T.L. Mader, S.M. Greising, S.K. Chen, M. Kyba, D.A. Lowe, and G.L. Warren. A moderate estradiol level enhances neutrophil number and activity in muscle after traumatic injury but strength recovery is accelerated. J. Physiol. 596(19): 4665-4680, 2018.PMID 30035314. PMC6166067.

Lindsay, A., A. Schmiechen, C.M. Chamberlain, J.M. Ervasti, and D.A. Lowe. Neopterin/7,8-dihydroneopterin is elevated in Duchenne muscular dystrophy patients and protects mdx skeletal muscle function. Exp. Physiol. 103 (7): 995-109, 2018. PMID 29791760. PMC6026059.

Collins, B.C., T.L. Mader, C.A. Cabelka, M.R. Iñigo, E.E. Spangenburg, and D.A. Lowe. Deletion of estrogen receptor alpha in skeletal muscle results in impaired contractility in female mice. J. Appl. Physiol. 124: 980-992, 2018. PMID 29345963. PMC5972463

O'Rourke, A.R., A. Lindsay, M.D. Tarpey, S. Yuen, P. McCourt, D.M. Nelson, B.J. Perrin, D.D. Thomas, E.E. Spangenburg, D.A. Lowe, and J.M. Ervasti.Impaired muscle relaxation and mitochondrial fission associated with genetic ablation of cytoplasmic actin isoforms. FEBS J. 285: 481-500, 2018. PMID 29265728. PMC5799018

McCourt, J.L., D.M. Talsness, A. Lindsay, R.W. Arpke, P.D. Chatterton, D.M. Nelson, C.M. Chamberlain, J.T. Olthoff, J.J. Belanto, P.M. McCourt, M. Kyba, D.A Lowe, and J.M. Ervasti. Mouse models of two missense mutations in actin-binding domain 1 of dystrophin associated with Duchenne or Becker muscular dystrophy.Hum. Mol. Genet. 27(3): 451-462, 2018. PMID 29194514. PMC5886145.

Torres, M.J., K.A. Kew, T.E. Ryan, E.R. Pennington, C.T. Lin, K.A. Buddo, A.M. Fix, C.A. Smith, L.A. Gilliam, S. Karvinen, D.A. Lowe, E.E. Spangenburg, T.N. Zeczycki, S.R. Shaikh, and P.D. Neufer.17?-Estradiol Directly Lowers Mitochondrial Membrane Microviscosity and Improves Bioenergetic Function in Skeletal Muscle. Cell Metab. 27(1):167-179.e7, 2018. PMID 29103922. PMC5762397.

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

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

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.