Michael R. Freeman, PhD
Professor, Department of Surgery, Harvard Medical School
David E. Retik Director of Basic Urologic Research, Urology Research, Boston Children's Hospital
DF/HCC Program AffiliationProstate Cancer
My research centers on understanding mechanisms of genitourinary pathology at the molecular and cellular level. Our current work centers on the role of EGF-like growth factors as soluble and membrane-anchored signaling molecules, on the intracellular signaling systems these factors regulate, and on the physiologic consequences of EGF-like growth factor pathway activation in cell regulation and disease. We have recently determined that one of the high-affinity activating ligands for the EGF receptor/ErbB1 tyrosine kinase, heparin-binding epidermal growth factor-like growth factor (HB-EGF), is a mechanically responsive gene in bladder smooth muscle cells. This finding, and other recently published data from our laboratory, implicate this growth factor in mechanisms of bladder wound healing and hypertrophic bladder growth. We have also recently identified HB-EGF and amphiregulin, an EGF-like growth factor with a similar domain structure to HB-EGF and a similar affinity for heparin, as products of the interstitial smooth muscle cells of the human prostate. We found the HB-EGF and amphiregulin genes to be coordinately expressed in benign and malignant human prostate tissue. These factors likely serve as directional signaling molecules between the fibromuscular stroma and the epithelial compartments of the prostate. The consequences of this directional signaling system in terms of signal transduction pathway activation, mitogenesis and cell survival regulation are under investigation.
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