Janice Dominov, Ph.D.

Scientist
Muscular Dystrophy; Skeletal Muscle Growth and Regeneration; Inflammation and Apoptosis in Muscle Disease
dominov@bbri.org

Research Summary

Muscular Dystrophy: The overall goal of our work is to define mechanisms that contribute to the pathogenesis of muscular dystrophies in order to identify targets for disease intervention. There are currently no cures for any of these devastating diseases. Our work includes studies on pathogenesis of Duchenne muscular dystrophy, a severe disease caused by abnormal levels of the protein dystrophin in muscle tissues, and congenital muscular dystrophy Type 1A (MDC1A), in which muscle weakness is evident from birth, caused by insufficient levels of the protein laminin alpha2 in the matrix material surrounding cells. We are studying inflammatory processes and key regulators of these (e.g. Toll-like receptors) that are induced early in congenital muscular dystrophy and could contribute to early muscle loss. In addition we are studying apoptosis pathways that can also play a role in regulating muscle survival in disease. Understanding the molecular events controlling muscle death and survival will better enable us to devise therapeutic strategies to minimize muscle loss, improve muscle repair, and thereby significantly enhance muscle function and patient quality of life.

 Muscle Regeneration: In response to trauma or muscle disease, muscle growth and repair occurs via activation of muscle progenitor cells that are resident among the muscle fibers (“satellite cells”). Subsets of these have qualities of self-renewing stem cells, producing both committed myogenic cells and more stem cells. Another goal of our work is to understand the biology of muscle stem cells and mechanisms of skeletal muscle growth and repair. Our focus is on factors involved in myogenic cell population expansion and chemoattractant signals that promote cell movement to sites of injury where they can effect muscle repair.

Research Support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the John W. Alden Trust.

Selected Publications

• Jeudy, S., Wardrop, K.E., Alessi, A. and Dominov J.A. 2011. Bcl-2 Inhibits the Innate Immune Response During Early Pathogenesis of Murine Congenital Muscular Dystrophy. PLoS ONE 6(8): e22369.
• Wardrop, K.E and Dominov J.A. 2011. Proinflammatory Signals and the Loss of Lymphatic Vessel Hyaluronan Receptor-1 (LYVE-1) in the Early Pathogenesis of Laminin alpha2-Deficient Skeletal Muscle. J. Histochem.Cytochem. 59: 167-179.
• Dominov, J.A., Kravetz, A.J., Ardelt, M., Kostek, C.A., Beermann, M.L. and Miller, J.B. 2005. Muscle-specific BCL2 Expression Ameliorates Muscle Disease in Laminin a2-Deficient, But Not Dystrophin-Deficient, Mice. Hum. Mol. Genet. 14: 1029-1040.
• Girgenrath*, M., Dominov*, J.A., Kostek, C.K. and Miller, J.B. 2004. Inhibition of Apoptosis Improves Outcome in a Model of Congenital Muscular Dystrophy. J. of Clin. Invest. 14: 1635-1639. (* equal contribution).
• Dominov, J.A., Houlihan-Kawamot, C.A., Swap, C.J. and Miller, J.B. 2001. Pro- and Anti-apoptotic Members of the Bcl-2 Family in Skeletal Muscle: a Distinct Role for Bcl-2 in Later Stages of Myogenesis. Developmental Dynamics 220: 18-26.
• Dominov, J.A., Dunn, J.J., and Miller, J.B. 1998. Bcl-2 Expression Identifies an Early Stage of Myogenesis and Promotes Clonal Expansion of Muscle Cells. J. Cell Biol. 142: 537-544.

PubMed:
Click here for a list of publications (searches the National Library of Medicine's PubMed database.)