Stem Cell Institute 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

Neruo-immuno Interface Lab

Bio

Dr. Blazar is a Regents Professor of Pediatrics in the Division of Blood and Marrow Transplant & Cellular Therapy and attends on the Pediatric Blood and Marrow Transplantation (BMT) service. Dr. Blazar is the recipient of the Children’s Cancer Research Fund Land Grant Chair in Pediatric Oncology to recognize his pioneering work in the development of novel immune-based therapies. He is the Founding Director of the Clinical and Translational Sciences Institute and the Founding Director of the Center for Translational Medicine.
Dr. Blazar received his MD from Albany Medical College. He completed a residency in Pediatrics and a fellowship in hematology/oncology and bone marrow transplantation at the University of Minnesota. Dr. Blazar joined the University of Minnesota faculty in 1985. He is board certified in Pediatrics and Hematology/Oncology.
Dr. Blazar is the recipient of National Institutes of Health (NIH) MERIT Awards from the National Heart, Lung, and Blood Institute as well as the National Institute of Allergy and Infectious Diseases. He is the Principal Investigator of the UMN Clinical and Translational Sciences Award (U54), NIH funded R01 grants, P01 Projects, a U19 grant subcontract and Leukemia and Lymphoma Translational Research grants focusing on BMT immunological studies. Dr. Blazar is the author of more than 725 manuscripts, which have appeared in premier peer-reviewed publications.

Research Summary

1. Graft-versus-host disease (GVHD) . GVHD is a multi-organ system disorder in which donor T cells recognize host alloantigens present on antigen-presenting cells and tissues in the context of an inflammatory response. Studies are directed toward identifying and modifying signals that drive or inhibit acute and chronic GVHD generation. These include the analysis of positive costimulatory molecules and negative regulators of the immune response that counterbalance positive costimulation as well as intracellular signaling and metabolic pathways that regulate these responses at the level of the GVHD target organ. We are examining cell-based therapies such as regulatory T cells (see below) in mice and in patients and myeloid-derived suppressor cells (see below). We have also used a newly developed model of chronic GVHD that results from T:B cooperativity, leading to alloantibody and subsequently, collagen deposition, culminating in multi-organ system injury and pulmonary and liver fibrosis. We have tested drugs and cell populations that affect this interaction, many of which have been brought into the clinic, one of which has received FDA approval. For approaches that reduce acute or chronic GVHD in mice, we are assessing their immune competency to malignant cells (to assess graft-versus-leukemia, GVL) and to pathogens.
2. Regulatory cells. A) regulatory T cells (Treg) . Using phosphoproteomics, metabolomics, micro-RNA/mRNA binding partners and flow cytometry, we have identified pathways that can be targeted to upregulate Treg potency in mice and humans. Proof-of-principle has been demonstrated in allogeneic and xenogeneic mouse models . Other studies are focused on genome engineering approaches that should optimize GVHD and autoimmune disease treatment. Knockout, transgenic and conditional inducible strains of mice are utilized along with 2-photon microscopy to identify mechanisms of in vivo suppression. B) Myeloid-derived suppressor cells (MDSC). We have developed techniques to differentiation and active MDSCs from normal hematopoietic sources in mice and humans. Our studies have shown in murine allogeneic GVHD systems that inflammasome activation converts MDSCs into immune stimulatory cells. Knockout of inflammasome components or inflammasome inducers have ameliorated this loss of function. Ongoing studies are examining the production of human MDSCs from inducible pluriopotent stem cells, with or without genome engineering approaches, for mechanistic purposes and potential future clinical trials.
3. T cell generation from induced pluripotent stem cells (IPSCs). In order to understand the optimal requirements for T cell anti-cancer or anti-pathogen responses, we have focused on reprogramming various human cell populations into thymic progenitor cells and mature T cells. Transcriptomics and epigenetics are investigated. Genome modification of IPSCs readily induces chimeric antigen receptor (CAR) expression that directs T cells to lymphoma cells. Using a model that incorporates a CAR used in the clinic for treating B cell malignancies and a transgenic strain that expresses human B cell antigens, cytokine release syndrome and neurotoxicity have been shown. Studies are being examined to explore different approaches to mitigate these side-effects.

Clinical Summary

Pediatric hematology/oncology
Bone marrow transplant
Graft-versus-host disease
Graft-versus-leukemia
Tumor immunotherapy

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

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
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 complete research portfolio is now extremely collaborative using the strength of team science to drive success of investigations designed to find new approaches to disease modeling and treatment.  I am the PI of a project using miPSC-derived limb bud progenitors to improve limb and digit regeneration and the Team PI of an NEI-funded RO1 with Prof. Ferrington in the Department of Ophthalmology generating an extensive biobank of iPSC-derived RPE from patients and eye donors with Dry Age-related Macular Degeneration.  These iPSC-RPE provide an excellent experimental model to study mitochondrial dysfunction in AMD and for screening compounds that may maintain or restore mitochondrial function in the RPE of patients with AMD.  I have also developed novel accelerated neural induction protocols to efficiently generate hiPSC-derived neuronal and glial cells for testing regenerative strategies to treat neural injury and disease.  The experience from this work is directly relevant to the current Harrington proposal where we will utilize a similar protocol to generate the cortical neurons from multiple hiPSC lines for drug screening.  The research team I lead also works on a range of other team projects including using iPSCs and blastocyst complementation to generate liver cells, using iPSCs and automation to investigate DMSO-free cryopreservation strategies for stem cells and stem cell-derived products and we are working with the Lions Gift of Sight Eye bank in Minneapolis to derive limbal stem cells from hiPSCs to support potential clinical use of these cells to repair corneal damage.

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

Andrew Grande, MD, is from the Twin Cities. He grew up in the Minneapolis lakes area and then later moved to St. Paul where he attended high school at St. Thomas Academy. He graduated from St. Olaf College (Northfield, MN) with a BA in chemistry and then attended the University of Minnesota Medical School. During college and medical school, Dr. Grande was active in research, working in the laboratories of Drs Esam El Fakahany, Virginia Seybold, and Walter Low. These experiences later culminated in a burning curiosity in and passion for using stem cells to treat stroke.

Dr. Grande completed his neurosurgical training at the Mayfield Clinic and University of Cincinnati. During his training, he worked very closely with Dr. John Tew, learning the nuances of trigeminal neuralgia treatment, including both microvascular decompression and radiofrequency ablation. He then went on to complete a fellowship with Mario Zuccarello, Andrew Ringer, and Todd Abruzzo at the University of Cincinnati in both endovascular and cerebrovascular neurosurgery. During this time, Dr. Grande was exposed to intracranial bypass surgery for treating moyamoya disease and to cutting-edge endovascular treatments such as the use of Onyx glue for treating cerebral aneurysms.

During his residency and then continuing into his fellowship, Dr. Grande was involved in stem cell research with Dr. Masato Nakafuku at Cincinnati Children's Hospital. Professor Nakafuku was one of the world's first to demonstrate neurogenesis in the hippocampus following stroke and he remains internationally recognized for his work with adult neurogenesis. In Nakafuku's laboratory, Grande's research focused primarily on reprogramming cells within the cerebral cortex to form neurons following stroke.

In 2010, Grande was the recipient of the William P. Van Wagenen Fellowship from the American Association of Neurological Surgeons. As a Van Wagenen Fellow, he traveled to Munich, Germany, where he completed a post-doctoral fellowship in the laboratory of Dr. Magdalena Gotz at Ludwig-Maximilians-Universitat. There he focused his research on identifying afferent connections to new neurons generated in the rodent cortex following a cortical layer specific injury.

Following his post-doctoral fellowship, Dr. Grande spent one month as a visiting neurosurgeon with Dr. Juha Hernesniemi in Helsinki, Finland.

Dr. Grande joined the University of Minnesota Department of Neurosurgery in 2011. His clinical interests are in treating cerebral vascular diseases, using either open vascular or endovascular techniques. He has specific interests in treating complex aneurysms, moyamoya disease, and trigeminal neuralgia.

Dr. Grande also directs the Stroke, Brain Injury, and Stem Cell Lab at the University of Minnesota. His research is focused on translating stem cell therapies for stroke from the bench to the bedside. Ongoing studies include exogenous cord blood stem cell transplantation for neuroprotection, reprogramming reactive astrocytes to form neurons, and characterizing normal adult neural stem cells found in the brains of humans and other large animals.

"It has always been a dream of mine to be a neurosurgeon in Minnesota, in particular at the University of Minnesota. I was born and raised here, my entire family is here and there is nothing I enjoy more than interacting with Minnesota patients. When contemplating places to work, I only considered Minnesota; I just knew I could be a better neurosurgeon here. I think there is something comforting in having a neurosurgeon with whom you have some connection.

Philosophy of Care:
My philosophy is to care for others as I would my mother, father, wife or child. I ask my patients to call me "Andy" because it's important to be on a first name basis with those who entrust their lives with me. While neurosurgery is a world of unpredictable fates, I am committed to each patient to do my absolute best all the time.

Education

• MD, University of Minnesota
• Residency in Neurosurgery, University of Cincinnati
• Fellowship in Vascular/Endovascular Neurosurgery, University of Cincinnati
• Fellowship in Neural Stem Cells and Neurogenesis, Ludwig-Maximilians University, Germany
• BA, St. Olaf College
• Emerging Physicians Leadership Program, University of Minnesota, Minneapolis, MN, 2014-2017

Professional Associations

• American Association of Neurological Surgeons
• American Heart/American Stroke Association
• Congress of Neurological Surgeons
• Congress of State Neurosurgical Societies
• European Society for Gene and Cell Therapy
• Facial Pain Association
• Frank H. Mayfield Society
• International Society for Stem Cell Research
• Minnesota State Neurological Society
• Minnesota Stroke Association
• Society of Neurointervention

Board Certifications

American Board of Neurological Surgeons Diplomate

Research Summary

Dr. Grande co-directs the Stroke, Brain Injury, and Stem Cell Lab at the University of Minnesota. His research interest is focused on translating stem cell therapies for stroke from "the bench to the bedside." Ongoing studies include exogenous cord blood stem cell transplantation for neuroprotection, reprogramming reactive astrocytes to form neurons, and characterization of normal adult neural stem cells found in the brains of humans and other large animals.

View PubMed List

Experts@Minnesota Profile

Service Summary

Minnesota Brain Injury Alliance 2011-present

• Board Member, elected 2013-present
• Advocacy Committee, appointed 2012-present

Minnesota Stroke Association 2011-present

• Partnership Committee, appointed 2011-present
• Conference Planning Committee, appointed 2011-present

Clinical Summary

Cerebral aneurysms, arteriovenous malformations (AVMs); carotid artery disease; trigeminal neuralgia; hemifacial spasm; intracranial/extracranial stenosis; moya moya disease; skull-base surgery; and stroke treatment.

Bio

Dr. Hallstrom received his PhD in Molecular Biology at the University of Iowa in 1999. He then did post-doctoral studies with Joseph Nevins at Duke University studying the control of Rb/E2F induction of proliferation and apoptosis. He joined the University of Minnesota in 2007 as an Assistant Professor in the Department of Pediatrics Hematology and Oncology division.

Research Summary

Immune Response in Pediatric Retinoblastoma Tumors
Our research interests focus on two major areas. The first is on the pediatric cancer retinoblastoma, which forms in the retina of children and infants. This cancer is caused by deregulation of the Rb/E2F pathway. We developed a novel mouse retinoblastoma model that develops rapid bilateral tumors in both eyes. Recently, we learned that these tumors express a gene expression "signature" that causes recruitment and accumulation of immune cells to these tumors. Since this is a highly sought after clinical goal, we are elucidating the mechanisms of immune cell recruitment so they can be targeted to kill cancer cells.

Epigenetics of Retinal Development
The second major research interest is in the epigenetic control mechanisms responsible for normal retinal development. These mechanisms can malfunction in pediatric retinoblastoma, and may be harnessed during retinal regeneration to produce new retinal cell types after they've been lost. In particular, we study the retinal function of an epigenetic regulator called UHRF2, which binds to a DNA epigenetic base called 5-hydroxymethylcytosine (5hmC). It is still poorly understood how 5hmC accumulates during retinal development and how this leads to proper retinal gene expression. Furthermore, 5hmC is widely lost in human tumors, including retinoblastoma, although the mechanism behind its loss is unclear, as is the anti-tumor effectiveness of restoring 5hmC. We utilize genome-wide approaches to understand the altered gene expression and 5hmC distribution in retinal cells lacking the Uhrf2 gene.

Research Summary

• Molecular mechanisms of damage during freezing

• Mechanisms of cryoprotection or cryoinjury
• Low temperature imaging of biological systems
• Preservation of cells and tissues
• Microfluidics and transport in microfluidic channels

Bio

Dr. Keirstead received her Ph.D. in neurophysiology from Queen's University, Kingston, Canada, where she studied the role of neck muscle motoneurons and sensory afferents in the control of head movement in the laboratory of Dr. P. Ken Rose. As a post-doctoral fellow in the laboratories of Dr. M. Rasminsky and Dr. A.J. Aguayo at McGill University, Dr. Keirstead examined the capabilities of retinal neurons to regenerate axons and form functional synaptic connections with central nervous system neurons. Dr. Keirstead came to the University of Minnesota as a research associate in the Department of Physiology where she used calcium imaging techniques to study the regulation of intracellular calcium ion concentration in glial cells by neurotransmitters in the laboratory of Dr. Robert Miller. She continued these studies as an assistant professor in the Department of Ophthalmology.
Dr. Keirstead is an assistant professor in the Department of Integrative Biology and Physiology, and the Administrative Co-director and member of the Stem Cell Institute.

Research Summary

Current research interests include:
The functional characterization of stem cells at various stages of differentiation and their functional integration into host tissue after transplantation.
My research involves the use of calcium imaging and electrophysiological techniques to examine the functional characteristics of stem cells in vitro as they differentiate into cells of various tissue types. This system provides a useful model for the development of functional characteristics of neurons and other cells in culture. Furthermore, our functional studies will permit us to better define the optimum degree of differentiation for the successful integration of transplanted stem cells into target tissues of host animals.

Bio

EducationDr. Kikyo, Associate Professor of Genetics, Cell Biology and Development, is a member of the Stem Cell Institute and the Masonic Cancer Center. He received his M.D. in 1987 and Ph.D. in 1993 from Tokyo University Medical School, Japan. He studied genomic imprinting in Dr. Azim Surani's laboratory at Wellcome/CRC Institute, University of Cambridge as a postdoctoral fellow. He then moved to Dr. Alan Wolffe's laboratory at NIH to start biochemical analysis of somatic cell nuclear cloning in Xenopus. He joined the University of Minnesota in 2000.

Research Summary

Nuclear remodeling, stem cells and cancer The long-term goal of Dr. Kikyo's group is to understand molecular mechanisms underlying pluripotency and cell differentiation. This study is expected to contribute to the development of regenerative medicine. His group has been using somatic cell nuclear cloning in Xenopus and induced pluripotent stem cells (iPSCs) of mouse and human to investigate pluripotency. His group established an in vitro model of Xenopus nuclear cloning by incubating egg extract and somactic cell nuclei. From this study, they identified the SWI/SNF ATPase ISWI, the nucleolar disassembly proteins FRGY2a/b, and the histone chaperon nucleoplasmin as key proteins for nuclear remodeling in nuclear cloning. More recently, his group fused the powerful transactivation domain of MyoD to the pluripotency protein Oct4 and radically improved the efficiency of making iPSCs. In addition, fusion of the same domain to the cardiac transcription factor Mef2c facilitates the reprogramming of fibroblasts to cardiomyocyte-like cells. His group continues the search for other key regulators necessary for the reprogramming of a cell differentiation state.

Bio

Dr. Kyba is a Professor of Pediatrics and Carrie Ramey / CCRF Endowed Professor in Pediatric Cancer Research in the Department of Pediatrics' Division of Blood and Marrow Transplant & Cellular Therapy. He is also an Endowed Scholar of the Lillehei Heart Institute, and an affiliate member of the Stem Cell Institute.
Dr. Kyba received his PhD degree from the University of British Columbia in 1998, and completed a postdoctoral fellowship in stem cell biology at the Whitehead Institute at MIT, Cambridge, MA in 2003. From 2003-2008, he was Assistant Professor of Developmental Biology at the University of Texas Southwestern Medical Center at Dallas, TX. He joined the faculty at the University of Minnesota in July 2008.
Dr. Kyba has published over 100 research manuscripts in scientific journals, including: Cell, Science, and Nature Medicine.

Research Summary

Dr. Kyba's research laboratory focuses on regulation of tissue-specific stem cells (hematopoietic and skeletal muscle) with a view towards ex-vivo expansion and therapeutic transplantation, as well as the derivation of tissue-specific stem cells from embryonic or iPS cells. He is also developing methods of performing BMT without irradiation or chemical conditioning. He has performed seminal experiments establishing the proof of principle for hematopoietic stem cell repopulation using embryonic stem cells and maintains an active program in the development of gene-targeting / genetic correction / cell therapy models.

Deriving therapeutic hematopoietic stem cells from embryonic stem cells.

ES cells are totipotent and capable of recapitulating all of the developmental events of embryogenesis. They are therefore theoretically the ideal source of cells for regenerative therapies. However, turning theory into practice is not straightforward, and very few successful models of such therapy exist. We have developed one successful model, based on regulated expression of members of the Hox family of transcription factors. Current work is focused on understanding how Hox genes regulate hematopoietic stem cell self-renewal and identifying regulatory circuits under Hox control.

Skeletal muscle stem cells and FSH muscular dystrophy

Certain degenerative diseases may be the result of ineffective self-renewal or differentiation of lineage specific stem cells. We are particularly interested in Fascioscapulohumeral Muscular Dystrophy (FSHD), a dominant dystrophy associated with a contraction of 4q subtelomeric repeats. Although the condition is almost certainly caused by derepression of a gene in the vicinity of 4q, the protein products of candidate genes in this area can not be detected overexpressed in patient muscle samples. Because muscle stem cells (satellite cells) are rare, proteins overexpressed specifically in satellite cells are unlikely to be identified in patient biopsies. We are testing the hypothesis that a Hox gene embedded within the 4q repeats, DUX4, causes FSHD when derepressed in muscle satellite cells.

Stem cell biology

Our long-term goal is to understand the pathways that control self-renewal vs differentiation of stem cells and to use this knowledge to understand degenerative diseases and to design and improve cell therapies. Our work is interdisciplinary, spanning iPS cell-based and animal models involving transplantation and tracking of somatic stem cells, vector development, CRISPR and TALEN-mediated genome editing, and cell-based screening and medicinal chemistry.

Bio

David Largaespada, PhD, is a full professor in the Departments of Pediatrics and Genetics, Cell Biology, and Development and the Associate Director for Basic Research in the Masonic Cancer Center at University of Minnesota. He is an authority on mouse genetics, gene modification, and cancer genes. He received his BS in Genetics and Cell Biology from the University of Minnesota, Twin Cities in 1987 and his PhD in Molecular Biology with Dr. Rex Risser at the University of Wisconsin-Madison in 1992. He did a post-doctoral fellowship at the National Cancer Institute working with world-renowned geneticists Dr. Nancy Jenkins and Dr. Neal Copeland, where the Leukemia and Lymphoma Society of America awarded him a post-doctoral fellowship. He joined the faculty of the University of Minnesota in late 1996. Dr. Largaespada currently holds the Hedberg Family/Children's Cancer Research Fund Chair in Brain Tumor Research. He was awarded the American Cancer Society Research Professor Award in 2013, the highest award given by the ACS.

Research Summary

Cancer genetics, Neurofibromatosis type 1 (Nf1), RAS signaling, insertional mutagenesis, pediatric cancer, brain tumors, osteosarcoma, transposons, Sleeping Beauty

Dr. Largaespada's laboratory is working to exploit insertional mutagenesis, and other functional genomics methods (e.g. CRISPR/Cas9) to identify and understand genes and pathways that govern cancer cell behavior. The Largaespada lab pioneered the use of a vertebrate-active transposon system, called Sleeping Beauty (SB), for insertional mutagenesis in mouse somatic cells. SB is being used as a tool for forward genetic screens for cancer genes involved in sarcoma, hepatocellular carcinoma, and mammary, gastro-intestinal tract and NF1 syndrome-associated nervous system cancers. A special emphasis of this work is on genes that promote metastasis or govern treatment sensitivity. Also, novel mouse models are being used for preclinical evaluation of new drugs and drug combinations for cancer treatment.

The identity of the mutations and other changes that drive the development of cancer must be determined for developing molecularly targeted therapeutics. Studies on human cancer exon re-sequencing suggest that a large number of mutations are present in breast and colorectal tumors (Sjoblom et al., Science, 2006). But, the identification of those changes that are selected for is going to be difficult because the number of "passenger" alterations not selected for during tumorigenesis is very large. The human cancer genome project promises to help reveal the typical landscape of genomic changes in human cancer, but must be supplemented with complementary large-scale approaches for functional validation of targets and genetic screens that can identify cancer gene candidates. The Largaespada lab has developed approaches, using the SB transposon system, which can meet these needs. They have shown that SB transposon vectors can be mobilized in the soma of transgenic mice allowing forward genetic screens for cancer genes involved in sarcoma and lymphoma/leukemia to be performed in living mice (Collier et al., Nature, 2005; Dupuy et al., Nature, 2005). The system requires creating mice that harbor both a transposon array of the insertionally mutagenic SB vector, T2/Onc, and express the transposase enzyme in the target somatic tissue. If transposition can induce cancer, then tumor DNA is studied by cloning insertion sites. These insertion sites are analyzed and one looks for T2/Onc insertions at reproducibly mutated genes, called common insertion sites (CIS). The system has now been altered so that tissue-specific transposon mutagenesis for cancer gene discovery in various organs can be accomplished. In one illustrative project mice harboring mutagenic (SB) transposons were crossed to mice expressing SB transposase in gastrointestinal tract epithelium (Starr et al., Science, 2009). All mice developed intestinal lesions including intraepithelial neoplasia, adenomas, and adenocarcinomas. Analysis of over 95,000 transposon insertions from these tumors identified 77 candidate gastrointestinal tract cancer genes. These genes were then compared to those mutated in human cancer, including colorectal cancer (CRC), or amplified, deleted or misexpressed in CRC, which allowed us to generate an 18 gene list that is highly likely to contain driver mutations for CRC. These genes include many of the most commonly known genes mutated in human CRC, such as APC, BMPR1A, SMAD4 PTEN, FBXW7, DCC, MCC, in addition to several novel CRC candidate genes that function in pathways widely expected to participate in CRC such as the proliferation, adhesiveness and motility of epithelial cells. Similar work has revealed drivers for hepatocellular carcinoma development (Keng et al, Nature Biotech, 2009). These studies demonstrate the power of transposon-based mutagenesis when combined with human studies for identifying the driver mutations that cause cancer. Similar results are accumulating for hepatocellular carcinoma, brain tumors, sarcomas and several other types of cancer.

Dr. Largaespada is also using mouse models of murine leukemia virus induced acute myeloid leukemia (AML) to identify and characterize genes that have a role in leukemia progression after disease is initiated by mutations relevant to human AML. This work also includes genetic studies of myeloid leukemia chemotherapy resistance and relapse. AML is the most common adult leukemia. It is clear that genetically defined subsets of AML have varying prognoses. AML frequently harbor chromosomal translocations that create fusion oncoproteins that act as transcription factors or constitutively active kinases. These fusion genes are thought to be insufficient, by themselves, for AML induction. Instead, secondary mutations cooperate with them to produce AML. The full set of cooperating mutations and their usefulness as therapeutic targets are important unknown quantities. The lab is exploring these questions by using MuLV mutagenesis in mice carrying specific human translocation fusion oncogenes known to play a role in human AML. The lab has developed MuLV-accelerated models of AML initiated by expression of the MLL-AF9 and AML1-ETO fusion oncoproteins (Bergerson et al., In Preparation; Yin et al., In Preparation). We have cloned 4,731 unique proviral insertions from 89 MuLV accelerated Mll-AF9/+ leukemia and 79 control MuLV-induced leukemia. Preliminary analysis reveals ~90 common insertion sites with many showing strong bias for Mll-AF9+ leukemias. Comparisons to expression microarray data on human AML with MLL gene translocations are in progress. These data may help to distinguish between genes that are direct targets of MLL-AF9, those that are a cause of AML development and those that cooperate with MLL-AF9 to induce AML.

In another area of AML research, we have sought to address the role of the activated NRAS oncogene in AML maintenance. We therefore developed Vav-tTA (expressed in hematopoietic cells) and TRE-NRASG12V transgenic lines in FVB/n mice. Interestingly, the doubly transgenic Vav-tTA plus TRE-NRASG12V mice developed a myeloproliferative disease very similar to human aggressive systemic mastocytosis (ASM) without other detectable hematopoietic tumors (Wiesner et al., Blood, 2005). To determine the ability of NRASG12D to cooperate with a fusion oncogene encoding an altered transcription factor we created triple transgenic Vav-tTA; TRE-NRASG12V; Mll-AF9 lines in C57BL/6J X FVB/n F1 mice. AML were obtained in triple transgenic mice. When we transplanted triple transgenic Vav-tTA; TRE-NRASG12V; Mll-AF9 AML into SCID mice we found that doxycycline (DOX) treatment via the drinking water could prevent AML engraftment or eliminate AML cells after letting them grow to full-blown leukemia in recipients. However, at least some of these mice develop DOX-resistant AML, which do not re-express the NRASG12V (Kim et al., Blood, 2009). This suggests that RAS oncoproteins may be good therapeutic targets, even in complex tumors induced in cooperation with another strong oncogene. The mechanisms for oncogene addiction are not clearly understood. We are currently exploring the mechanism of AML cell death after NRAS oncogene suppression, the mechanism by which rare AML cells escape death in this context, and interactions between RAS targeted therapies and conventional chemotherapy.

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

Dr. Lund is interested in the use of hematopoietic stem cell transplantation (HSCT) primarily for patients with inherited metabolic disorders, like Adrenoleukodystrophy (ALD), Hurler syndrome (MPS-1H), Hunter syndrome, Metachromatic Leukodystrophy, and others. He studies the onset of disease, biomarkers of disease, mechanism of disease, and how HSCT improves the disease process. His work both in his research laboratory and with his patients has created many new approaches to treatment, which will ultimately make HSCT safer and more effective.
"Yes, we're saving lives. But that's not enough. I want to improve the quality of life for these kids, and that's where I'm focusing my energy."

Research Summary

Dr. Lund's research focuses improving the outcomes for all patients undergoing blood and marrow transplantation by increasing the speed at which hematopoietic stem cells reconstitute the immune system after transplant. He also works to increase our understanding the pathophysiological processes underlying inherited metabolic diseases. One area Dr. Lund is exploring is how an autoimmune reaction may trigger the cerebral form of adrenoleukodystrophy (cALD), the most serious form of ALD. This study represents the largest screening for immune-reactivity in cALD ever performed, and further research could help identify ALD patients with immune-reactivity prior to the onset of cALD.

Clinical Summary

Clinical Interests
Adrenoleukodystrophy; Bone marrow transplant; Hurler syndrome; Peripheral blood stem cell transplant; Umbilical cord blood transplant

Bio

Dr. McKenna holds the American Red Cross Chair in Transfusion Medicine and is Director of the Division of Transfusion Medicine. He also serves as the Scientific and Medical Director of Molecular and Cellular Therapeutics (MCT), the University's cGMP facility, as well as Laboratory and Medical Director of the University of Minnesota Medical Center Clinical Cell Therapy Laboratory and the director of the fellowship program in Transfusion Medicine/Blood Banking. McKenna is an active AABB member, serving on the board of directors for four years and leading the AABB Cellular Therapy Section Coordinating Committee for several years. He was a key investigator in the NIH-sponsored Production Assistance for Cellular Therapies contract from 2003-2015.

Research Summary

Interests include umbilical cord blood research, quality assurance/quality control in cellular therapy, and translational research/clinical scale-up of biotherapeutics.

Publications

• Mamo T, Dreyzin A, Stroncek D, McKenna DH. Emerging biomarkers for monitoring chimeric antigen receptor T-cell therapy. Clin Chem. 2024 Jan 4;70(1):116-127. doi: 10.1093/clinchem/hvad179. 
• Mamo T, Hippen KL, MacMillan ML, Brunstein CG, Miller JS, Wagner JE, Blazar BR, McKenna DH. Regulatory T cells: A review of manufacturing and clinical utility. Transfusion. 2022 Apr;62(4):904-915. doi: 10.1111/trf.16797.
• Walton K, Fernandez MR, Sagatys EM, Reff J, Kim J, Lee MC, Kiluk J, Hui JYC, McKenna D, Hupp M, Forster C, Linden MA, Lawrence NJ, Lawrence HR, Pidala J, Pavletic SZ, Blazar BR, Sebti SM, Cleveland JL, Anasetti C, Betts BC. Metabolic reprogramming augments potency of human pSTAT3-inhibited iTregs to suppress alloreactivity. JCI Insight. 2020 Apr 7. pii: 136437. doi: 10.1172/jci.insight.136437.
• Hussein E, DeFor T, Wagner JE, Sumstad D, Brunstein CG, McKenna DH. Evaluation of post-thaw CFU-GM: clinical utility and role in quality assessment of umbilical cord blood in patients receiving single unit transplant. Transfusion. 2019 Nov 22. doi: 10.1111/trf.15592. 
• McKenna D. Challenges in the cGMP manufacturing of MSCs for multicenter academia trials. Transfusion (2016);56(4):18S-9S. doi: 10.1111/trf.13565.
• Courville EL*, Singh C*, Yohe S, Linden MA, Naemi K, Berger M, Ustun C, McKenna R, Dolan M. Patients with a history of prior chemotherapy and isolated del(20q) with minimal myelodysplasia have an indolent course. *co-first authors. Am J Clinical Pathol.2016 Apr; 145(4):459-66.

Bio

Dr. McLoon received her PhD from the Department of Anatomy at the University of Illinois Medical Center, followed by postdoctoral studies with Dr. Ray Lund at the University of Washington and Medical University of South Carolina. She is a tenured Professor in the Department of Ophthalmology and Visual Neurosciences. She studies pharmacologic approaches to the treatment of eye movement disorders in children, specifically strabismus and nystagmus. She is focused on the cell biology and muscle stem cell populations within the muscles that move the eyes in the orbit, the extraocular muscles, to understand their sparing in diseases such as Duchenne muscular dystrophy and what goes awry in eye movement disorders. Recently she has added an interest in sex differences in retinal function and how this relates to neuropsychiatric disease.

Expertise
Strabismus, nystagmus, muscle stem cells, muscle injury, muscle regeneration, craniofacial muscles, neurotrophic factors

Research Summary

My laboratory focuses on understanding the potential mechanisms for two types of eye movement disorders: strabismus and nystagmus. Untreated these result in decreased visual acuity. Both involve the ocular motor system and the specialized skeletal muscles that move the eye, the extraocular muscles (EOM). We focus on the ability of retrogradely transported neurotrophic factors to alter the function and structure of the ocular motor system with the goal of developing a permanent therapeutic approach for these movement disorders. We have used RNAseq data to identify potential new therapeutic targets for development of treatments.

A second focus is the study of the muscle stem cell populations in the EOM that cause their differential sparing in degenerative disorders such as muscular dystrophy and amyotrophic lateral sclerosis. We have identified a specific stem cell, expressing Pitx2, which we have implicated in this differential sparing. Further work will focus on using these stem cells to prevent limb muscle degeneration in these currently untreatable diseases.

Finally, we have started a new project looking at the electroretinogram (ERG) in various mouse models of disease. Our recent studies show a significant difference in ERG characteristics in a mouse model of schizophrenia compared to controls, suggesting a specific method by which differences in the brain can be measured in the retina.

Research interests:
Development of pharmacologic treatments for strabismus and infantile nystagmus syndrome
Extraocular muscle cell biology
Sparing of the extraocular muscles in muscular dystrophies
Molecular control of extraocular muscle properties and how these are affected in strabismus and nystagmus
Sex differences in the electroretinogram

Teaching Summary

Courses
NSC 5203 Neuroscience of Vision
NSC 8321 Career Skills for Neuroscientists

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

Bio

Dr. Branden Moriarity is currently an Associate Professor in the Department of Pediatrics, Division of Hematology/Oncology. He graduated from Saint Olaf College in 2007 with a BA in Biology, Chemistry, and Biomolecular sciences. He received his PhD in Molecular, Cellular, Developmental Biology & Genetics at the University of Minnesota in 2012. From 2012-2014 he was a post doctoral fellow in David Largaespda's lab, where he worked on identifying the genetics of pediatric sarcomas. He joined the Department of Pediatrics Faculty in 2014.

Dr. Moriarity runs a basic/translational research laboratory working to develop novel cellular therapeutics for gene therapy and cancer immunotherapy with the goal of translating new therapeutics to the clinic. To accomplish these goals, the Moriarity lab uses cutting edge genome engineering technologies, including CRISPR/Cas9, base editor technology, transposons, and rAAV. These tools allow for high frequency gene knockout, gene knock-in, induction of targeted sequence changes, and activation and/or repression of endogenous gene expression. Target cells for engineering include T cells, B cells, NK cells, Monocytes, and hematopoietic stem cells. In addition to developing cellular based therapeutics, the Moriarity lab also performs preclinical drug testing for pediatric cancers, such as osteosarcoma, in order to launch new clinical trials using antibody therapies rather than toxic chemotherapy.

Research Summary

Preclinical Drug Testing, Genome Engineering, Gene Therapy, and Cancer Immunotherapy.
Dr. Moriarity runs a basic/translational research laboratory working to develop novel cellular therapeutics for gene therapy and cancer immunotherapy with the goal of translating new therapeutics to the clinic. To accomplish these goals the Moriarity lab uses cutting edge genome engineering technologies including CRISPR/Cas9, base editor technology, transposons, and rAAV. These tools allow for high frequency gene knockout, gene knock-in, induction of targeted sequence changes, and activiation and/or repression of endogenous gene expression. Target cells for engineering include T cells, B cells, NK cells, Monocytes, and hematopoietic stem cells. In addition to developing cellular based therapeutics, the Moriarity lab also performs preclinical drug testing for pediatric cancers, such as osteosarcoma, in order to launch new clinical trials using antibody therapies rather than toxic chemotherapy. 

Research Summary

Our current interests include the intrinsic mechanisms of thalamic development and the roles of thalamic input in neocortical development. We extensively use mouse genetics and in vivo gene delivery into developing embryos. Efforts in our lab are directed at two major goals: We are trying to understand how the developing thalamus produces different neuronal populations that later form distinct nuclei. We have characterized the spatial and temporal heterogeneity of progenitor cell populations in the thalamus. We are now trying to reveal molecular mechanisms that regulate such heterogeneity. Some of our recent works have determined the roles of Sonic hedgehog and Wnt signaling in this process, and how these intrinsic patterning mechanisms eventually affect the formation of thalamic nuclei in mice. We are trying to examine the roles of thalamocortical projections in the formation of functionally and anatomically distinct sensory areas in neocortex. To dissect local patterning mechanisms operating within neocortex and extrinsic mechanisms conveyed by the thalamic input, we are analyzing mutant mice in which certain thalamic nuclei are specifically alerted in size or the entire thalamocortical projections are compromised. Using these mice, we will determine the precise roles of thalamic afferents in neocortical development.

Bio

Dr. Osborn is an Assistant Professor in the Department of Pediatrics, Division of Blood and Marrow Transplantation. He is also a member of the Cancer Center. Dr. Osborn received his PhD degree from the University of Minnesota in 2009 in the laboratory of Dr. Bruce R. Blazar, MD.

Research Summary

Dr. Osborn's current research is focused on gene and cellular therapy for disorders treated by hematopoietic cell transplantation including: Fanconi anemia, epidermolysis bullosa, and Hurler syndrome. This involves utilizing a patient's own cells for precision gene targeting and correction of their disease causing mutation. Genome editing nucleases and multiple terminally differentiated and stem cell populations are utilized towards optimizing ex vivo cellular therapies.
Gene Therapy
- Non-viral gene transfer for the treatment of inborn errors of metabolism.
Genome Editing
- Correction of disease specific mutations in a precise manner using homologous recombination.
Cellular Therapy
- Ex vivo correction of murine and human adult stem cells.

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

Dr. Parr is interested in finding new therapies for spinal cord injury. As such, she is Principal Investigator in the Parr Laboratory and at the U of M's Stem Cell Institute (SCI) She is also a faculty member in the Graduate Program in Neuroscience and SCI and has several active, ongoing research projects funded by organizations such as the Minnesota Spinal Cord Injury and Traumatic Brain Injury Research Grant Program, the Morton Cure Paralysis Foundation, the University of Minnesota Foundation and Vertex Pharmaceuticals. She is also site leader for several business and industry clinical trials.

Regenerative Medicine Minnesota Grant Video

Dr. Parr is listed as the first author for 8 of the 15 articles she's had published in peer-reviewed journals and 7 of the 9 articles in non-peer reviewed publications. She authored two books chapters and is named in two provisional patents.

She earned her BSc in Life Sciences with Honours and her MD from Queen's University in Kingston, Ontario. Dr. Parr participated in the Neurosurgical Residency Program at the University of Manitoba in Winnipeg. She then went on to complete a Neurosurgical Research Fellowship as a PhD candidate in the Institute of Medical Science's Clinical Investigator Program at the University of Toronto, Ontario. She completed her Neurosurgical Residency Program at the University of Toronto and a Complex Neurosurgical Spine Fellowship in the Department of Neurosurgery of the University of Miami and Jackson Memorial Hospital in Miami, FL.

Dr. Parr is board-certified in both the United States and Canada and has been a faculty member since 2010. She has been the Medical Director for Spinal Neurosurgery at the U of M since 2017.

As a committed leader in neurosurgery, Dr. Parr has held numerous leadership positions in professional organizations, including as a board member of the American Association of Neurological Surgeons, Chair of the Northwest Quadrant for the Council of State Neurological Societies, and president of the Minnesota Neurological Society. She is particularly committed to bringing more women into neurosurgery and has held several leadership positions in the American Association of Neurological Surgeons/Congress of Neurological Surgeons Joint Section on Women in Neurosurgery.

As a sought-after speaker, Dr. Parr has served as visiting professor or presenter for numerous organizations and during national/international meetings.

In the News

• U of M, Hennepin Healthcare study gives hope to those told they would never walk again
• University of Minnesota Researchers Created 3D-printed Implant that Restores Function in Spinal Cord
• U of M may have spinal injury breakthrough with 3D printing
• University of Minnesota reports breakthrough in 3-D printing for spinal cord repair
• New 3D-printed device could help treat spinal cord injuries
• Spine surgeon leader to know: Dr. Ann Parr of UMN Medical School

Executive Assistant

Nicole Falk
Administrative Phone: 612-624-6666 (then hit 4 for the Academic Office)
Administrative Email: falkx188@umn.edu

Research Summary

Dr. Parr's research currently centers around transplanting neural stem cells grown from a patient's own skin into the injured spinal cord. She has an active translational research laboratory at the Stem Cell Institute. She is interested in examining mechanisms of functional recovery using techniques such as histology and immunohistochemistry, cell tracking through magnetic resonance imaging, and animal modeling.

In the Media

• U Researchers 3-D Print Device for Spinal Cord Repair (10-17-2018 U of M Medical School Medical Bulletin)
• A look at the "bag of tricks" the U of M is creating to help patients with spinal cord injury (9-24-2018 Neurosurgery Department News)
• U of M may have spinal injury breakthrough with 3D printing (8-9-2018 KARE 11 TV News Story)
• University of Minnesota Medical School researchers collaborate in cutting-edge cell bioengineering and unique 3D-printing techniques (8-9-2018 Neurosurgery Department News)

View PubMed List

Clinical Summary

Spine; General neurosurgery; Complex spinal surgery; Minimally invasive spinal surgery

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.

Research Summary

Research in the Rivera-Mulia Lab is focused on 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.

Bio

Dr. Santi is a Professor Emeritus.

Bio

Dr. Bhairab Singh is an Assistant Professor in the Department of Rehabilitation Medicine, Division of PM&R, Medical School at the University of Minnesota. He received his PhD degree from the Center for Cellular and Molecular Biology, India in the area of Cell Biology and Biochemistry. Dr. Singh's laboratory focuses on studying the molecular regulation of mammalian heart regeneration and cardiovascular disease modeling.  His laboratory uses a number of cutting-edge technologies including tissue engineering, stem cell technology and in vivo models. 

Honors and Awards

University of Minnesota, USA

• Top Basic Science Abstract Award, American Heart Association, AHA 2019
• Dr. Marvin, and Hadassah Bacaner Research Award in Cardiology 2016
• Best Scientist Award in Cardiovascular Sciences 2016
• Best Post-Doctoral Award in Cardiovascular Sciences 2013

Center for Cellular and Molecular Biology, India

• NMITLI Fellowship, CSIR 2009 
• Senior Research Fellowship, CSIR 2008 Bhairab N Singh 2
• Dr. Amjad Rahi Award in Eye Research, LVPEI 2007
• Junior Research Fellowship, CSIR 2006

Jawaharlal Nehru University, India

• Department of Biotechnology Fellowship, DBT, India 2003
• Summer Fellowship at Panacea Biotech Ltd. 2002

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

Jakub Tolar, MD, PhD is the dean of the University of Minnesota Medical School and a Distinguished McKnight University Professor in the Department of Pediatrics, Blood and Marrow Transplant & Cellular Therapy. He is also the vice president for Clinical Affairs at the University of Minnesota, board chair for University of Minnesota Physicians and co-leader of M Health Fairview, the joint clinical enterprise among the University of Minnesota Medical School, University of Minnesota Physicians and Fairview Health Services. An internationally recognized physician and researcher, Dr. Tolar is known for his care of patients with recessive dystrophic epidermolysis bullosa. His research is focused on developing cellular therapies for rare genetic disorders. Originally from the Czech Republic, Dr. Tolar received his medical education (MD) in Prague at Charles University. In 1992, he came to the University of Minnesota, where he received his PhD in Molecular, Cellular & Developmental Biology and Genetics.

Research Summary

Dr. Tolar's research focuses on finding new ways to treat children with lethal, inherited diseases. He is also looking for safer and more effective gene therapy for diseases such as epidermolysis bullosa, mucopolysaccharidosis type I (Hurler syndrome), Fanconi anemia, and dyskeratosis congenita. Additional research interests include reducing the negative effects of stem cell transplantation (such as using mesenchymal stromal cells for graft-versus-host disease); creation and use of induced pluripotent stem cells; gene therapy using gene addition (with viral vectors and trasposons); and gene editing (with synthetic nucleases to repair genes).

Clinical Summary

Blood and marrow transplantation; Gene therapy for correction of genetic diseases

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. Andrew Venteicher specializes in minimally invasive, endoscopic endonasal, and traditional open microsurgical approaches to cranial base tumors and cerebrovascular diseases. He is the neurosurgical director of the Center for Cranial Base Surgery, which focuses on diagnosis and comprehensive treatment for patients with tumors along the base of the brain, pituitary gland, and brainstem.

Dr. Venteicher earned his BA from the University of Pennsylvania in Mathematics, Biochemistry and Economics, as well as an MS in Chemistry. He attended Stanford for both his MD and PhD in Biophysics, trained at Harvard Medical School for his residency, and was selected for the prestigious cerebrovascular and cranial base fellowship at the University of Pittsburgh.

Professional Associations

• American Association of Neurological Surgeons
• Congress of Neurological Surgeons
• North American Skull Base Society
• Society of Neuro-Oncology

Executive Assistant

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

Research Summary

On the research side, Dr. Venteicher is part of a new translational research initiative between the U's Medical School and the Masonic Cancer Center that is exploring the genomics of brain tumors. His laboratory focuses on using new molecular techniques to understand how and why brain tumors develop and resist chemotherapy and radiation treatment. Translational research efforts such as these are of particular importance to identify new treatment options for patients with these diseases. He will one of the first to move into the new multidisciplinary consortium located at the Masonic Cancer Center Discovery Labs in the Malcolm Moos Health Sciences Tower on campus.

View PubMed list

View Experts@Minnesota Profile

Venteicher Lab

Bio

John E. Wagner, MD, is a Professor in the Department of Pediatrics, Division of Blood and Marrow Transplant & Cellular Therapy. He is the Founding Director of the new Institute of Cell, Gene and Immunotherapeutics at the University of Minnesota. Co-Director of the Center for Translational Medicine, and holds two endowed chairs—Children's Cancer Research Fund/Hageboeck Family Chair in Childhood Cancer Research, and the University of Minnesota McKnight-Presidential Chair.
Dr. Wagner's research is focused on the development of novel cell therapies for treatment of life threatening diseases. Examples include the development of regulatory T cells that could be used in the treatment of autoimmunity, organ graft rejection as well as graft-versus-host disease, thymic progenitors to repair damaged immune systems, cardiac myoblasts to reverse heart failure, skeletal myoblasts to repair or replace dystrophic muscle fibers in muscular dystrophy, and expansion of the blood-forming stem cell to speed blood and marrow recovery after high doses of chemotherapy and radiation. Dr. Wagner is best known for his pioneering work on the use of placental/cord blood as a source of stem cells for transplantation – a procedure that has now been performed in more than 50,000 patients worldwide.

Research Summary

Dr. Wagner's research has focused on the development of new treatment approaches for life-threatening diseases for which conventional treatments are unsatisfactory. Dr. Wagner is recognized for pioneering the use of double umbilical cord blood transplantation in adults and embryo selection to insure an HLA matched, healthy child ('savior sibling') for another child in need of transplant. He is also a leader in the use of regulatory T cells to prevent rejection and graft versus host disease, expanded blood forming stem cells to speed blood and marrow recovery, novel conditioning regimens to dramatically increase the chance of cure of patients with Fanconi anemia and bone marrow derived stem cells to repair the skin in severely affected children with Epidermolysis Bullosa.

1. Umbilical Cord Blood Transplantation in Children and Adults
Ex vivo expansion of hematopoietic stem cells
Double unit transplantation
Non-myeloablative preparative therapies
Co-infusion of T-regulatory cells
Graft vs. Leukemia Effector Therapies

2. Fanconi anemia
Novel preparative therapies
Gene therapy - multipotent adult stem cell
Phenotype-genotype correlations (collaboration with Rockefeller University)
Pathophysiology

3. Multipotent Adult Stem Cells (MAPC) in tissue repair
Translational development/large scale manufacture of MAPC
Evaluation of MAPC therapeutic potential in congenital and acquired disorders

Research Summary

Our research interests pertain to leukocyte biology with a current focus on natural killer (NK) cells. Various receptors expressed on the surface of leukocytes that are critical for their function can be rapidly downregulated in expression upon cell activation by “ectodomain shedding”. This process is primarily mediated by the membrane-associated metalloprotease ADAM17. Ectodomain shedding operates in part as a negative feedback mechanism to restrain leukocyte function and ADAM17 serves as a broad acting regulatory checkpoint that controls NK cell activity in a polyfunctional manner. Our goal is to manipulate this process to enhance NK cell function in killing tumor cells and virus-infected cells. 

Experts@Minnesota Profile (https://experts.umn.edu/en/persons/bruce-walcheck)
PubMed Article List (https://pubmed.ncbi.nlm.nih.gov/?term=walcheck%20b)