Regulation of Muscle Growth by the TGF-β family

Se-Jin Lee, MD, PhD

Johns Hopkins University School of Medicine (Baltimore, MD)

Dr. Lee is a Professor in the Department of Molecular Biology and Genetics, at the Johns Hopkins University School of Medicine (Baltimore, MD).

Past Projects

Objective: 
Elucidate the regulatory components involved in the control of muscle growth by myostatin and other TGF-β family members

Myostatin (MSTN) is a secreted protein that acts to suppress skeletal muscle growth. As a result, there has been considerable interest in developing strategies to target MSTN signaling to increase muscle growth and regeneration in patients with muscle degenerative diseases. In recent work, we have demonstrated that other signaling molecules related to MSTN also limit muscle growth in vivo and that the capacity for increasing muscle growth by targeting this general signaling pathway is much greater than previously appreciated. The goal of this project is to conduct a detailed comparative analysis of the effects of various potential inhibitors of this signaling pathway with respect to their potency and efficacy. Our focus will be on engineered biologics based on proteins that can bind and inhibit the activities of various members of the TGF-ß superfamily, including MSTN. Because these binding proteins have varying specificities with respect to the spectrum of signaling molecules that they are capable of blocking, our studies will provide essential information regarding the optimal specificity of therapeutic agents aimed at promoting muscle growth and regeneration in patients with muscular dystrophy. Genetic approaches employing transgenic animals over-expressing follistatin, an MSTN inhibitory gene, will be performed in parallel to further assess the hypothesis that the modulation of MSTN may have therapeutic efficacy in dysferlinopathy.

Although the Jain Foundation is no longer financially supporting this project, Dr. Lee is continuing this line of research under funding from other sources. The Jain Foundation is still interested in the outcome of these studies, and Dr. Leecontinues to update us with regard to the status of the research.