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Administration
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Research Interests
Research in our laboratory is in three areas: 1. TGF-b signaling and tissue homeostasis. 2. Regulation of hepatocyte apoptosis. 3. Molecular basis of nuclear reprogramming.
- We are investigating the role of the TGF-b signaling pathway in the regulation of organ homeostasis and in the pathobiology of disease. Defective TGF-b signaling contributes to a wide range of human diseases including cancer, fibrosis and cardiovascular disease. The association of this signaling pathway with such diverse disease conditions highlights its importance in the regulation of basic cellular processes as such cell proliferation, differentiation and the regulation of extracellular matrix production. We are using a combined conventional transgenic and gene knock out approach to determine the role of this pathway in regulating these processes. We have generated and are using strains of mice overexpressing a constitutively active TGF-b ligand, a dominant-negative TGF-b type II receptor, a constitutively active TGF-b type I receptor, Smad 4 and Smad 7 targeted to the liver, kidney and adipose tissue. These strains of mice are being used in conjunction with Smad 3 null mice to assess the importance of this signaling pathway in these organs.
- We are investigating the regulation of hepatocyte apoptosis using a combined transgenic and knock-out approach. We have generated a unique strain of transgenic mice in which we can regulate both the degree of hepatocyte proliferation and the kinetics of hepatocyte cell death by simply altering the carbohydrate content of the diet. These mice are being crossed into various null backgrounds in an effort to determine the molecular basis of the regulation of hepatocyte cell death.
- A newly initiated effort in the lab, in association with the laboratory of Dr. David Garbers, is focused on investigating the molecular basis of nuclear reprogramming in mammals. Efforts are underway to investigate this process in mice and to extend the technology to rats. Efforts to extend gene knock-out technology to the rat are continuing by developing strategies to derive and maintain pluripotent rat embryonic stem cell lines.
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