Henry F. Epstein, M.D.
Professor

Henry F. Epstein, M.D.

About the Lab

Dr. Epstein's laboratory is studying the role of chaperone-mediated folding in regulatory mechanisms of development and disease.

Biochemical and genetic studies on the C. elegans model as well as in various fungal species have demonstrated that a novel molecular chaperone is required for the proper folding, assembly, and function of myosins and myosin-like protein motors. The chaperone protein, named UNC-45 after the canonical gene in C. elegans, binds the well-known molecular chaperone Hsp90 as well as myosin. In mice and humans, two UNC-45-like genes are present and encode closely related but distinct isoforms. One isoform is present in many cell types and appears necessary for cell division and membrane fusion; the other isoform is expressed predominantly in heart and skeletal muscle and is necessary for sarcomere organization. The UNC-45 mammalian homologues may prove to be important targets for genetic and pharmacological intervention in certain cancers and heart failure.

Selected Publications:

Landsverk, M.L., Li, S., Hutagalung A.H., Najafov, A., Hoppe, T., Barral, J.M. and Epstein, H.F.  The UNC-45 Chaperone Mediates Sarcomere Assembly through Myosin Degradation in C. elegans.  J. Cell Biol. 177:205-210, 2007.

Guo, W., Chen, D., Fan, Z., and Epstein, H.F. Differential turnover of myosin chaperone UNC-45A isoforms increases in metastatic human breast cancer.  J. Mol Biol. 

Ni, W., Hutagalung, A.H., Li, S. and Epstein, H.F. The myosin-binding UCS domain but not the Hsp90-binding TPR domain of the UNC-45 chaperone is essential for function in Caenorhabditis elegans.   J. Cell Sci.  124:3164-3173, 2011.

Benian G.M. and Epstein H.F.  Caenorhabditis elegans muscle: a genetic and molecular model for protein interactions in the heart.  Circ Res.  109:1082-1095, 2011.

Chen, D., Li, S., Singh, R., Spinette, S., Sedlmeier, R. and Epstein, H.F. Dual function of the UNC-45b Chaperone with myosin and GATA4 in cardiac development.  J. Cell Sci (in press).

Kaiser, C.M., Bujalowski, P.J., Ma, L., Anderson, J., Epstein, H.F., & Oberhauser A.F. Tracking UNC-45 Chaperone-Myosin Interaction with a Titin Mechanical Reporter. Biophys J (in press).

 

Link to my publications on pubmed (in addition to the one on the sidebar):

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