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Department of Pharmacology
Marcelo G. Kazanietz, Ph.D.

Education:

1989	Ph.D. (Pharmacology)	University of Buenos Aires, Argentina
1990-1995	Postdoctoral Fellow	Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH, Bethesda, MD

Research Summary:
Our main research interest is in the area of signal transduction in carcinogenesis. We use state-of-the-art cellular and molecular approaches to dissect the intracellular pathways activated by the lipid second messenger diacylglycerol (DAG) and phorbol esters, natural products with tumor promotion activity that activate protein kinase C (PKC) isozymes. Our current research focuses on three areas. First, we study signaling pathways that mediate the pro-apoptotic effect of individual PKC isozymes in prostate cancer models, focusing on MAPK cascades and Akt signaling. Second, we are characterizing a novel family of “non kinase” receptors for phorbol esters and DAG, the "chimaerins". Chimaerins have Rac-GTPase Activating Protein (GAP) activity that can be tightly regulated by DAG and by complex mechanisms involving protein-protein interactions and intracellular translocations. Our experimental hypothesis is that chimaerin RacGAPs play a crucial role in the regulation of Rac-mediated responses, such as actin-cytoskeleton reorganization, cell cycle progression, malignant transformation and metastasis. Third, we are studying the epigenetic effects of Polycyclic Aromatic Hydrocarbons (PAHs) derivatives, which are known to be causative agents in human lung cancer, focusing on their effects in signal transduction pathways (PKC and others) and cell cycle control. Our challenge is to understand these complex signaling mechanisms with the ultimate goal of finding novel targeting molecules for cancer therapeutics using cellular, genetic and pharmacological approaches.