Our laboratory studies the molecular mechanisms by which TGFB family proteins suppress growth, focusing on Mullerian Inhibiting Substance (MIS) as a model. After purifying MIS protein and cloning its gene, we cloned the genes for its type I and type II receptors and a number of other receptors of this transmembrane serine/threonine kinase family, and used homologous recombination to uncover their early embryonic function using human ovarian and breast carcinomas as targets for MIS, the laboratory discovered that MIS produced G1 arrest and apoptosis by inducing p16 in ovarian cancer, and by inducing NFKB and regulating the specific IEX-1S isoform in breast cancer cell lines. Preclinical trials of MIS are underway in preparation for phase I clinical trials in human ovarian cancer patients.
We also study the molecular mechanisms of sex differentiation and of foregut development to correct congenital anomalies of the trachea and esophagus. As she and her colleagues search for gene defects causing congenital anomalies, they hope to design in utero pharmacologic therapies to reduce the severity of the abnormalities at birth.