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Dr. Cohen is a research associate at the Center for Genetic Muscle Disorders at Kennedy Krieger Institute and the Department of Neurology at the Johns Hopkins University School of Medicine.
Dr. Cohen obtained her undergraduate degree from State University of New York at Buffalo and her doctoral degree in pharmacology from University of Maryland. Her thesis work focused on identifying genomic elements that regulate selective gene expression at neuromuscular synapses. Dr. Cohen completed postdoctoral fellowship training at the NIH where she studied the function of proteins making up the nuclear envelope and developed transgenic mouse models for disorders of the nuclear envelope, including Emery-Dreifuss muscular dystrophy and Limb Girdle muscular dystrophy (LGMD) 1B.
She then worked at Children’s National Medical Center in the laboratory of Terence A. Partridge, D. Phil, where she studied the regenerative potential of muscle stem cells in mouse models of Duchenne muscular dystrophy (DMD) and LGMD. In 2013, Dr. Cohen joined the laboratory of Dr. Kathryn R. Wagner, MD, PhD, at the Center for Genetic Muscle Disorders at Kennedy Krieger Institute, where she continues her studies in molecular mechanisms underlying muscular dystrophies.
Dr. Cohen investigates molecular mechanisms underlying muscle diseases, including Duchenne and Limb Girdle muscular dystrophies. While at the NIH, she developed transgenic mouse models of nuclear envelopathies that affect skeletal muscle function. Mutations in one nuclear envelope protein, lamin A/C result in Emery-Dreifuss muscular dystrophy and Limb Girdle muscular dystrophy 1B. Lamin A/C regulates chromatin structure and gene expression and thus plays an important role in the proliferation of satellite cells, the muscle fiber-associated stem cells that repair injured skeletal muscle. Dr. Cohen showed that mutations in lamin A/C cause it to form aberrant protein complexes with lamina-associated proteins 2alpha, but genetically silencing this protein can reverse the muscle growth deficits.
More recently, Dr. Cohen’s research has focused on modulating inflammation in muscular dystrophies. Myopathies such as Duchenne and Limb Girdle muscular dystrophy 2B are particularly prone to chronic inflammation. With mounting evidence suggesting that chronic inflammation is detrimental to muscle function, many investigators are currently examining the use of anti-inflammatory agents as possible therapies for these disorders. While at Children’s National Medical Center, Dr. Cohen used several approaches to show that modulating inflammation can improve muscle regeneration.
She showed that celastrol, a naturally occurring plant extract, can potentiate the growth of dystrophic muscle cells in vitro. Further, genetically ablating Myd88, an intracellular messenger activated in innate immunity, improved the pathology and muscle function in a mouse model of Duchenne muscular dystrophy. More recently, she showed that interleukin 1beta, secreted from infiltrating classically activated macrophages, is a major contributor to regeneration deficits in dystrophic muscle, and using a neutralizing antibody to interleukin 1beta can potentiate muscle growth.
Another research interest has been on the role of the TGFbeta pathway on muscle growth and regeneration. Dr. Cohen showed that lamin A/C and an interacting protein, MAN1, regulate the nuclear entry and efflux of TGFbeta signal mediators, Smads2/3 and thus play an important role in regulating gene expression of Smad2/3 targets. Additionally, overactivity of Smads2/3 contributes to muscle growth defects in lamin A/C-mutated muscle cells. More recently, Dr. Cohen has been focused on another member of the TGFbeta family, myostatin, which is expressed specifically in muscle, and when inhibited can greatly potentiate muscle mass.
Extracellular myostatin inhibitors are currently undergoing clinical trials for therapeutic use for muscular dystrophies. Dr. Cohen investigated the role of a naturally occurring intracellular inhibitor of myostatin, Smad7, and showed that mice carrying genetic disruption of Smad7 show severe deficits in muscle growth and regeneration. Thus, Smad7 may be a potential intracellular target of myostatin inhibition for treating muscle disorders.