Department of Cell Biology, Neurobiology & Anatomy Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226-0509
Phone: (414) 456-8459 FAX: (414) 456-6517 email: jlough@mcw.edu
Education: PhD, Washington University, St. Louis, 1975 Postdoctoral, Massachusetts Institute of Technology
Graduate Programs: Program in Cell and Developmental Biology
Research Area: Cell and molecular biology of early heart development
Research in this laboratory is currently focused on adult cardiac regeneration, using principles learned from our previous investigations of heart development in the embryo. We are using two independent albeit complementary approaches to address this problem.
The first approach extends from our previously documented finding that embryonic tissues, specifically precardiac endoderm and mesoderm, can induce embryonic stem cells (ESCs) to differentiate into cell populations enriched in beating cardiac myocytes (Rudy-Reil & Lough, 2004). We are now extending this finding by identifying extracellular growth factors secreted by precardiac endoderm and mesoderm that mediate cardiogenic induction of ESCs. A related goal is to identify downstream transcription factors in ESCs which regulate developmental steps - i.e. specification and differentiation - of the cardiogenic process. Using these approaches we are obtaining sufficient numbers of ESC-derived cardiac myocytes to enable evaluation of their ability to re-muscularize and improve function of infarcted myocardium in a mouse model.
The second approach is to test the hypothesis that Tip60 (Tat Interactive Protein, 60 kD), a protein enriched in embryonic as well as adult myocardium (Lough, 2002), functions to keep adult cardiac myocytes in a non-proliferative state. This possibility is supported by our finding that although homozygous Tip60 -/- knockout mice cannot develop past the 64-128 cell stage of embryonic development (Kim et al., manuscript in preparation), Tip60 +/- heterozygous mice exhibit increased tumor formation (Amati B, Lough J, et al.). This suggests that Tip60 functions as a tumor suppressor, which in the context of the adult myocardium indicates a possible role in negative cell cycle regulation.
Selected Publications: