Jonathan D. Smith, PhD
Professor, Cellular and Molecular Medicinesmithj4@ccf.org 216.444.2248 (o) 216.444.9404 (f)
Member, GU Malignancies Program
I am applying my expertise in cellular lipid metabolism and lipoprotein metabolism to a new area of interest in prostate cancer. The project I have started in my lab is based on the novel hypothesis that different aspects of HDL metabolism have opposite effects on prostate cancer (CaP) cell signaling and sterol metabolism. Specifically, we hypothesize that: 1) systemic HDL can deliver cholesterol to CaP cells via the HDL receptor, SR-BI, which fuels CaP cell growth by providing cholesterol needed for cell division, and perhaps in some cells as a metabolite for de novo androgen synthesis; and 2) the generation of nascent HDL by CaP cells using extracellular apoAI and cellular ABCA1 can remove cholesterol from CaP cells and inhibit AKT signaling, which will retard CaP cell growth. Understanding these opposite activities of HDL metabolism on CaP cells may allow for the development of new therapies and for nutritional, pharmacological, and life style recommendations to prevent
and/or delay the progression of CaP.