Muscle Cell Biology T32 Fellow
Prior Training
University of Rochester, B.S. Cell and Developmental Biology
Program
MBIDP, Cell and Developmental Biology
Mentor
April Pyle, Ph.D.
Skeletal muscle progenitor cells (SMPCs) differentiated from human pluripotent stem cells (hPSCs) are difficult to expand while maintaining their stemness. This makes it difficult to use them for transplantation in cell therapies for muscular dystrophies. Recently, the Pyle lab has established a GFP reporter hPSC line that reflects the expression of PAX7, a critical factor for muscle cell stemness. My project focuses on using SMPCs derived from this reporter cell line to screen for small molecules that can support the growth and maintenance of PAX7+ progenitor cells.
Muscle Cell Biology T32 Fellow
Prior Training
UC Davis, B.S. in Neurobiology, Physiology, and Behavior
Program
Molecular, Cellular & Integrative Physiology
Mentor
Stephen Cannon, M.D., Ph.D.
Our lab studies the pathogenic basis of skeletal muscle excitability disorders due to ion channel mutations, with an emphasis on a group of channelopathies resulting in attacks of weakness known as periodic paralysis. My research centers around one such potassium channelopathy, known as Andersen-Tawil Syndrome, which affects both skeletal and cardiac muscle excitability. My work aims to understand the physiological basis which triggers such attacks, and characterize the phenotypic manifestation of the disease in both skeletal and cardiac muscle.
MBI T32 Fellow
Prior Training
UC Irvine, B.S.
Program
MBIDP, Cell and Developmental Biology
Mentor
Melissa Spencer, Ph.D.
I am interested in using CRISPR/Cas9 editing as a therapeutic strategy for Duchenne muscular dystrophy. I am also focusing on alternative editing platforms such as CRISPR/CpfI.
Muscle Cell Biology T32 Fellow
Prior Training
Colby College, B.S.
Research Assistant- Louis Kunkel Lab Harvard Medical School
Program
MBIDP, Molecular Biology Interdepartmental Doctoral Program
Mentor
April Pyle, Rachelle Crosbie-Watson
My research involves working with skeletal muscle progenitor cells derived from hPSCs, and human muscle stem cells to develop improved in vitro and in vivo systems for modeling human skeletal muscle diseases. These systems can then be used to test gene and stem cell therapies in a humanized skeletal muscle environment.
Muscle Cell Biology T32 Fellow
Prior Training
University of Illinois Urbana-Champaign, B.S.
Program
MBIDP, Cell and Developmental Biology
Mentor
Atsushi (Austin) Nakano
My research focuses on investigating the mechanisms underlying myocardial maturation and the application of stem cell therapy in cardiac regeneration. One aspect of my studies is trying to understand the contribution of non-genetic factors in hES-derived cardiomyocyte maturation and the role of cellular mechanosensing during development and differentiation.
Qatar Foundation Fellow
Prior Training
UCLA, Research Scholar
Qatar University, B.S. in Biological Sciences
Program
Molecular, Cellular & Integrative Physiology
Mentor
April Pyle, Ph.D.
Skeletal muscle is one of few organs in the human body that has its own stem cell niche capable of repopulating muscle fibers upon injury. Satellite cells (SCs), which lie between the sarcolemma of muscle fiber and basal lamina, form an adult stem cell source for muscle repair. In Duchenne Muscular Dystrophy (DMD), a devastating genetic disease characterized by muscle wasting, the SCs are rendered dysfunctional following continuous muscle insult. The migratory nature of these progenitors is of particular interest in the settings where systemic delivery in cell-based therapy is desired. My research will examine the migratory potential of skeletal muscle progenitor cells (SMPCs) and investigate their functionality in skeletal muscle niche.
Prior Training
UC Irvine, B.S. Developmental and Cell Biology
Program
Molecular Biology Interdepartmental PhD Program (MBIDP)
Home area: Cell and Developmental Biology
Mentor
Rachelle Crosbie-Watson, PhD
My research focuses on developing therapeutic approaches to treat various forms of muscular dystrophy. In collaboration with the Molecular Screened Shared Resource (MSSR) at UCLA, I am developing a high throughput screen to identify small molecules that can upregulate sarcospan expression. Overexpression of sarcospan in the Duchenne muscular dystrophy mouse model is shown to improve muscle health and function by stabilizing the muscle membrane. Thus, identifying small molecules that can regulate sarcospan expression may lead to new treatments for the muscular dystrophies.
Prior Training
Aix Marseille University/UMRS-910
(Marseille, France) Ph.D. degree
Mentor
M. Carrie Miceli
Assessment of new drugs to promote exon skipping for Duchenne Muscular Dystrophy. This project is to extend preclinical translational data in support of the therapeutic development path in relation to exon skipping for DMD. We have identified drugs that target RyR regulated Ca+ flux (RyR-antags) and synergize with AON in promoting human DMD exon 51 and mouse exon 23 skipping and rescue of an internally truncated, but partially functional dystrophin protein (Kendall et al, 2012). Now, we have secured industry partnerships that enable us to test proprietary compounds targeting these same pathways, but which have potential for even better therapeutic window(s) and commercialization.
Muscle Cell Biology T32 Fellow
Prior Training
Plymouth State University, B.S., Botechnology
Dartmouth College, Ph.D., Genetics
Mentor
Stanley Nelson, M.D.
Duchenne and Becker muscular dystrophy (DMD and BMD, respectively) patients often present with heterogeneous patterns of dystrophy within muscle biopsies. In some cases, small clusters of muscle fibers (known as revertant fibers) almost look healthy compared to the surrounding diseased tissue. The existence of these revertant fibers are thought to slow disease progression, as the muscle retains more functional muscle fibers. The mechanisms that drive the formation and maintenance of these fibers are still largely unknown. My research focuses on developing protocols to investigate the heterogeneity of DMD and BMD muscle biopsies at a single cell/single nucleus resolution. These tools will be instrumental in identifying the mechanisms that can act in vivo to modify disease progression, muscle repair mechanisms, and the formation of revertant fibers. Such studies may also yield the discovery of new druggable targets for the treatment of DMD and BMD.
Prior Training
University of Michigan, M.S., Ph.D.
Mentor
Rachelle Crosbie-Watson, Ph.D.
Muscle weakness in Duchenne muscular dystrophy is caused by the loss of a protein called dystrophin, which serves to protect the muscle cell membrane during contraction. I study the interaction of protein complexes that help stabilize the cell membrane, and how these complexes can be used to prevent membrane damage in Duchenne muscular dystrophy.
Eli and Edythe Broad Stem Cell Research Center Fellowship
Muscle Cell Biology T32 Fellow
Prior Training
Arizona State University
Mentor
April Pyle, Ph.D.
My research uses human pluripotent stem cells (HPSCs) to make skeletal muscle progenitor cells (SMPCs) as a means to repair and replace damaged muscle fibers. Dr. Pyle’s laboratory is at the forefront of using these cells to deliver dystrophin protein to mouse models of Duchenne Muscular Dystrophy in xenograft transplantations. I seek to test and improve upon the best differentiation protocols in the scientific and preclinical field to create SMPCs with robust myogenic potential and serve the role of an endogenous adult muscle stem cell. Much of my work is currently characterizing the muscle derived from HPSCs, maturing these cells via modeling the muscle stem cell niche, and identifying small molecules and growth factors to further drive their myogenesis.
Prior Training
University of Minnesota, Ph.D.
Mentor
Rachelle Crosbie-Watson, Ph.D.
My research focuses on characterizing cardiac fibrosis in Duchenne muscular dystrophy-associated cardiomyopathy. Fibrosis, on the excess deposition of extracellular matrix prevents efficient cardiac contraction, diminishes regenerative capacity, and is a major barrier to cell-based therapies. The central hypothesis I am testing is that the structural, mechanical, and proteomic profiles of the cardiac ECM in the context of muscular dystrophy represent a distinct pathological microenvironment that is resistant to remodeling and negatively impacts cardiomyocyte function.
Prior Training
UC Irvine, B.S., Biological Sciences,
UCSF, M.S., Physical Therapy,
USC, Ph.D., Biokinesiology
Mentor
Rachelle Crosbie-Watson, Ph.D.
My current research is focused on the role of skeletal muscle extracellular matrix (ECM) in muscle pathology associated with Duchenne muscular dystrophy (DMD). I study ECM biophysical and biochemical alterations that may contribute to DMD muscle pathology, and how the ECM is altered following gene and exon skipping therapies for DMD. Given the importance of the muscle microenvironment in directing resident cell function, research into ECM alterations in DMD will enhance our understanding of DMD muscle pathology and may provide insight into new therapies that facilitate and enhance the formation of new skeletal muscle.
Prior Training
University of Miami, Ph.D.
Mentor
April Pyle, PhD
During the progression of DMD, the constant damage of patients' skeletal muscle results in abnormal activation of the resident skeletal muscle stem cells (satellite cells, SCs), which leads to their exhaustion and eventually the loss of muscle regeneration. Therefore, to cure DMD, it is imperative to replenish patients with SCs or skeletal muscle progenitor cells (SMPCs) to support their long-term muscle maintenance. In this regard, human pluripotent stem cells (hPSCs) are a superior source for obtaining SMPCs due to their remarkable self-renewal and differentiation capabilities. My project is focusing on devloping an efficient and defined protocol to differentiate hPSCs to generate SMPCs following developmental myogenesis and understand the indentity of the in vitro-derived SMPCs. The ultimate goal is to use hPSC-derived SMPCs in cell transplantation therapy to cure DMD.
Prior Training
University College London, M.S.,
Johns Hopkins University, B.S.
Mentor
Melissa Spencer, Ph.D.
We are developing a CRISPR/Cas9-mediated gene editing platform to correct the reading frame for up to 60% of Duchenne muscular dystrophy patients. We are applying our platform to DMD human induced pluripotent stem cells and can restore dystrophin protein and function after differentiation to cardiac and skeletal muscle. Furthermore we are currently developing in vivo strategies for our gene editing approach.
Prior Training
Wellstone Fellow
Mentor
Andrea Hevener, Ph.D.
I am interested in mitochondrial dynamics and quality control in regulating skeletal muscle metabolism and the pathophysiology of muscular dystrophy. Early diagnosis of Duchenne muscular dystrophy (DMD) could enable early treatment that delay the symptoms and improve the quality of life. My current research focuses on detecting novel serum biomarkers to assess disease progression and response to therapies in mouse muscle dystrophy models and exploring the physiological role of these biomarkers in vivo.
