Training Fellows

Joana Capote

Joana Capote

Prior Training
Universidad Central de Venezuela, Licenciado

Program
Molecular, Cellular & Integrative Physiology

Mentor
Melissa Spencer, Ph.D.

My work in Dr. Spencer's lab is focused on defining the role of Osteopontin (OPN) expression on the regulation of the course of the Duchenne Muscular Dystrophy (DMD) pathology. My project is devoted to identifying the sources of OPN expression in muscle and to studying the effect that OPN exerts on the regulation of the muscle inflammatory, fibrotic and regenerative processes involved in the DMD pathology. Moreover, I aim to identify the pathways involved in these effects by using a combination of in vivo and in vitro approaches.

Brian McMorran, MS

Brian McMorran, M.S.

Prior Training
UCLA, MS

Program
Pathology and Laboratory Medicine

Mentor
Linda G. Baum, M.D., Ph.D.

Brian’s research focuses on the function and regulation of glycosylation during muscle development and in muscle disease. Research thus far has demonstrated distinct patterns of glycosylation in healthy human muscle compared to dystrophic muscle; similarly, changes in glycosylation which occur following muscle human muscle differentiation are distinct from those observed for mouse muscle cells, emphasizing the species-specific nature of some forms of glycosylation. The overarching goals of this project are to determine how changes in glycans on human cells affect function of healthy and dystrophic muscle, and to identify novel therapeutic approaches that will restore proper glycosylation, membrane stability, and sarcolemmal adhesion in dystrophic muscle.

Cynthia Shu, B.S.

Cynthia Shu, B.S.

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, Ph.D.

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.

Derek Wang, B.S.

Derek Wang, B.S.

Prior Training
UCLA, B.S. in Microbiology, Immunology, & Molecular Genetics

Program
Microbiology, Immunology, and Molecular Genetics

Mentor
Carrie Miceli, Ph.D.

Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive disorder primarily caused by large frameshifting deletions in the DMD gene that result in a loss of dystrophin protein expression. Antisense oligonucleotide (AO)-mediated exon skipping shows promise as a therapeutic approach by restoring the DMD reading frame, allowing internally deleted but partially functional dystrophin production and restoration of the dystrophin associated glycoprotein complex. We identified Dantrolene, an FDA approved drug, as an enhancer of exon skipping when administered with AO. We aim to establish optimal Dantrolene formulation, delivery route, Dantrolene/AO dose, and test efficacy of long term treatment of optimal Dantrolene/AO on exon skipping and muscle function in vivo, establish efficacy and dosing of combinatorial therapy in multiple exon 51-skippable patient-derived fibroblasts differentiated into myotubes, and establish a DMD xenograft model system for studying DMD in vivo.

Courtney Young, M.S.

Courtney Young, M.S.

Prior Training
University College London, M.S.,
Johns Hopkins University, B.S.

Program
MBIDP, Cell and Developmental Biology

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.

Florian Barthélémy, Ph.D.

Florian Barthélémy, Ph.D.

Prior Training
Aix Marseille University/UMRS-910
(Marseille, France) Ph.D. degree

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.

Elizabeth Gibbs, Ph.D.

Elizabeth Gibbs, Ph.D.

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.

Michael Hicks

Michael Hicks, Ph.D.

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.

Ekaterina Mokhonova, Ph.D.

Ekaterina Mokhonova, Ph.D.

Mentor
Carrie Miceli, Ph.D.

Development of combination therapy to enhance antisense mediated exon skipping for Duchenne Muscular Dystrophy. Assessment activity of dantrolene in combination with antisense oligonucleotide in vitro in DMD patient-derived myotube cultures and in vivo in mdx mice.

Michelle S. Parvatiyar, Ph.D.

Michelle S. Parvatiyar, Ph.D.

Prior Training
University of Miami (Ph.D.)

Mentor
Rachelle Crosbie-Watson, Ph.D.

My project focuses on correcting cardiac dysfunction and pathology associated with muscular dystrophies. Our approach involves the overexpression of a naturally occurring protein, sarcospan with a known role in stabilizing cell membranes in the absence of dystrophin, the primary defect in Duchenne muscular dystrophy. We have shown that overexpression of sarcospan increases laminin binding in the heart and upregulates utrophin, a protein, which compensates for dystrophin loss. Significantly, we have shown improved cardiac function in dystrophin-deficient mdx mice overexpressing sarcospan, suggesting its promise as a therapeutic strategy to restore DMD-associated cardiac dysfunction.

Kristen Stearns-Reider, Ph.D., P.T.

Kristen Stearns-Reider, Ph.D., P.T.

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.

Haibin Xi

Haibin Xi, PhD

Prior Training
University of Miami, PhD

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.