Faculty

Bio

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

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

Research Summary

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

Bio

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

Research Summary

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

Clinical Summary

General cardiology; Advanced heart failure; Orthotopic heart transplant

Research Summary

The Gordon Lab is interested in how cell surface receptors convert signals from extracellular stimuli like mechanical force into a biological response, as dysregulation in a cell's force-sensing ability can lead to disease. We use X-ray crystallography and other biophysical methods to ask what "mechanosensors" look like in order to understand the range of structures nature uses to sense forces of different magnitudes and in different contexts, and hopefully identify potentially novel therapeutic targets. We also use and develop single molecule and cell-based assays based on magnetic tweezers to apply forces to mechanosensors to probe how mechanosensors are converted from an "off" to "on" state. We measure both magnitudes of forces to effect a biological response and are developing methods to probe the corresponding structural changes that occur. Finally, we are developing general signaling assays to help us map mechanosensor domains, understand differences between on and off states, and search for new potential mechanosensors.

Bio

Areas of interest

Skeletal muscle physiology, exercise physiology, orthopaedic trauma, regenerative rehabilitation

Degrees

2015 Mayo Clinic, Rochester, MN; Postdoctoral Fellowship

2011 University of Minnesota, Minneapolis, MN; PhD Rehabilitation Science

2006 Canisius College, Buffalo, NY; MS Health and Human Performance

2004 Winona State University, Winona, MN; BS Exercise Science - Athletic Training

Positions and Academic Appointments

2015 - 2018, Adjunct Assistant Professor of Physiology, Mayo Clinic

2015 - 2018, Research Physiologist in Extremity Trauma and Regenerative Medicine, US Army Institute of Surgical Research

2018 - 2022, Assistant Professor of Kinesiology, University of Minnesota

2020 - 2022, McKnight Land-Grant Professor, University of Minnesota

2021 - Present, Faculty Center for Clinical Movement Science, University of Minnesota

2022 - Present,  Graduate Faculty Rehabilitation Science, University of Minnesota

2022 - Present, Associate Professor of Kinesiology, University of Minnesota

2022 - Present, Henry L. Taylor-Arthur S. Leon Professorship in Exercise Science and Health Enhancement

Professional Memberships and Activities

2004 - Present, American College of Sports Medicine

2011 - Present, American Physiological Society - Member of eBook Committee

2018 - Present, Orthopaedic Research Society - Co-Chair Women's Leadership Forum

2019 - Present, Tissue Engineering & Regenerative Medicine Society - Chair Musculoskeletal TWIG

Associate Editor, Connective Tissue Research

Research Summary

Research

Skeletal Muscle Plasticity and Regeneration Laboratory

Current research interests and long-term scientific goals of the laboratory revolve around the plasticity and regeneration of skeletal muscle, in efforts to mitigate the devastating functional limitations of limb salvage and traumatic muscle injuries. The laboratory examines the musculoskeletal and neuromuscular systems in efforts to understand and develop effective strategies to address the deleterious effects of complex traumatic muscle injuries, namely volumetric muscle loss.

Selected publications

1. Complete list of peer-reviewed articles

Teaching Summary

Teaching

Exercise Physiology (KIN 4385)

Applied Exercise Physiology (KIN 5122)

Seminar: Exercise Physiology (KIN 8122)

MS & PhD Advising Statement

Bio

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

Research Summary

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

Bio

Dr. Kamdar is an Assistant Professor of Medicine in the Cardiovascular Division of the Department of Medicine at the University of Minnesota. She received her M.D. from the University of Minnesota Medical School. She completed her training in internal medicine and cardiovascular disease at the University of Minnesota through the Physician-Scientist Training Pathway, in which she pursued a Ph.D. in Integrative Biology and Physiology. She completed her advanced heart failure, heart transplant, and mechanical circulatory support fellowship at the Cleveland Clinic. Her clinical and research interests focus on cardiomyopathy associated with neuromuscular disorders, such as muscular dystrophies, and clinical and translational research in mechanical circulatory support.

Research Summary

Cardiac Calcium Regulation Muscular Dystrophy Associated Cardiomyopathy Human induced pluripotent stem cell research Myocardial structural proteins Mechanical circulatory support Kamdar Lab Website

Clinical Summary

Advanced heart failure, Advanced hemodynamic support, Cardiac transplant/Mechanical Circulatory Support, Heart failureHeart transplantation and regeneration, Hypertrophic cardiomyopathy, Mechanical circulatory support, Muscular dystrophy associated cardiomyopathy, Right ventricular dysfunction, Women's heart health

Bio

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

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

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

Bio

Dr. Karachunski is board certified neurologist with special qualification in pediatric neurology. He is specializing in neuromuscular medicine. Dr. Karachunski is a director of comprehensive multidisciplinary Muscular Dystrophy Association Care Center. Dr. Karachunski treats adult and pediatric patients with variety of neuromuscular disorders including muscular dystrophies and related disorders, spinal muscular atrophies, hereditary polyneuropathies, myasthenia gravis and myositis. He directs clinical research unit at the Paul and Sheila Wellstone muscular dystrophy center.

Clinical Summary

Specialties: Muscular Dystrophy, Neuromuscular Medicine, Nerve and Muscle Pathology, EMG

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

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. 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

Expertise

Skeletal muscle biology in aging, health and disease

Professional Associations

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

Research Summary

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

Research Funding Grants

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

Publications

2023:

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

2022:

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

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

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

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

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

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

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

2021:

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

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

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

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

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

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

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

Teaching Summary

Grant Writing: RSC 8206