Research Interests

I have studied the molecular mechanisms by which TGFB family proteins suppress growth, focusing on Mullerian Inhibiting Substance (MIS) as a model. After purifying and cloning MIS, my colleagues and I cloned its heterodimeric receptors and a number of other receptors of this transmembrane serine/threonine kinase family and used homologous recombination to uncover their early embryonic function. We proposed that human ovarian and endometrial and later breast and prostate carcinomas would be targets for MIS and used human cancer cell lines growth-arrested by MIS to elucidate its signal transduction pathway. Having found that primary human ovarian cancer cells from patients express MIS receptors and respond to MIS, my laboratory has undertaken preclinical trials of MIS in preparation for phase I clinical trials in human ovarian cancer patients. I also have applied my experimental work on molecular mechanisms of sex differentiation to the care and surgical reconstruction of infants with intersex abnormalities. My colleagues and I have applied an understanding of foregut development to correct congenital abnormalities of the trachea and esophagus. We are searching for pathway gene defects causing congenital diaphragmatic hernia with the goal of designing in utero pharmacologic therapies to reduce their severity at birth.

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Section 42: Medical Physiology and Metabolism