Department of Molecular Biology & Genetics

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Se-Jin Lee - Professor Molecular Biology & Genetics 725 N. Wolfe Street 802 PCTB Baltimore, MD 21205 Office: 410-614-0198 Fax: 410-614-7079 sjlee@jhmi.edu

Assistant:	Christine Gazurian

Regulation of mammalian development and adult tissue homeostasis by growth and differentiation factors
The primary interest of my laboratory is to understand the role of signaling molecules in regulating embryonic development and adult tissue homeostasis. We have focused on the superfamily of secreted proteins that are structurally related to transforming growth factor-ß (TGF-ß). Members of this growth factor family have been shown to play important roles in regulating the development and function of many different tissues, and as a result, many of these factors have shown enormous therapeutic potential for a wide range of clinical applications. Using molecular genetic approaches, we have identified a large number of novel mammalian TGF-ß family members that we have designated growth/differentiation factors (GDFs). We have been using a variety of experimental approaches, including genetic manipulation of mice, to attempt to understand the precise biological functions of these molecules. We are particularly interested in understanding the roles of these molecules in regulating tissue growth. Much of our work has focused on a molecule that we have designated myostatin. We have shown that myostatin is expressed specifically in developing and adult skeletal muscle and that mice engineered to lack myostatin exhibit dramatic increases in skeletal muscle mass throughout the body. Based on these and other studies, we believe that myostatin normally acts to block skeletal muscle growth. We are currently attempting to elucidate the mechanism of action of myostatin as well as the mechanisms by which the activity of myostatin is regulated. Our long term goal is to attempt to exploit the biological properties of myostatin to develop novel therapeutic strategies for treating patients with muscle degenerative and wasting conditions, such as muscular dystrophy, sarcopenia, and cachexia resulting from diseases like cancer, AIDS, and sepsis.

Relevant Publications:	Se-Jin Lee, Lori A. Reed, Monique V. Davies, Stefan Girgenrath, Mary E.P. Goad, Kathy N. Tomkinson, Jill F. Wright, Christopher Barker, Gregory Ehrmantraut, James Holmstrom, Betty Trowell, Barry Gertz, Man-Shiow Jiang, Suzanne M. Sebald, Martin Matzuk, En Li, Li-fang Liang, Edwin Quattlebaum, Ronald L. Stotish, and Neil M. Wolfman (2005) Regulation of muscle growth by multiple ligands signaling through activin type II receptors. Proc. Natl. Acad. Sci., USA. 102:18117-18122. PubMed Abstract Markus Schuelke, Kathryn R. Wagner, Leslie Stolz, Christoph Hubner, Thomas Riebel, Wolfgang Komen, Thomas Braun, James F. Tobin, and Se-Jin Lee (2004) Myostatin mutation associated with gross muscle hypertrophy in a child. New Engl. J. Med. 350:2682-2688. PubMed Abstract Zimmers, T.E., M. V. Davies, L. G. Koniaris, P. Haynes, A. F. Esquela, K. N. Tomkinson, A. C. McPherron, N. M. Wolfman, S.-J. Lee (2002) Induction of Cachexia in Mice by Systemically Administered Myostatin. Science. 296:1486-1488. Science Abstract:Full Text McPherron, A.C., Lawler, A.M., and Lee, S.-J. (1999) Regulation of anterior/posterior patterning of the axial skeleton by growth/differentiation factor-11. Nature Genet. 22:260-264. PubMed Abstract McPherron, A.C., Lawler, A.M., and Lee, S.-J. (1997) Regulation of skeletal muscle mass in mice by a new TGF - ß superfamily member. Nature. 387:83-90. PubMed Abstract

Graduate Program Affiliations	Biochemistry, Cellular & Molecular Biology (BCMB) Cellular and Molecular Medicine (CMM) Human Genetics and Molecular Biology