Manabu Kurokawa, Ph.D.
Assistant Professor of Pharmacology and Toxicology
Hanover, NH 03755
Phone: (603) 650-1251
Dr. Kurokawa's research interests lie in the fields of programmed cell death and cancer. Chemotherapeutic agents typically function by triggering a cell death program known as apoptosis, which promotes the release of cytochrome c from the mitochondria into the cytoplasm and stimulates activation of cell-death proteases, caspases, through formation of a complex called the apoptosome. However, cancer cells are often able to acquire resistance to these drugs and evade death by somehow blocking mitochondrial cytochrome c release and/or inhibiting caspase activation. Dr. Kurokawa's laboratory employs a panel of cancer cell lines which are resistant to specific anti-cancer agents, to include kinase inhibitors, as a model system to gain more insight into the molecular mechanism(s) underlying acquired resistance. These cell lines have been isolated by continuous culture in the presence of the drugs at clinically relevant therapeutic concentrations. This approach mimics the relevant clinical setting where patients receive the chemotherapeutic agent on a daily basis. Using the resistant cell lines as tools, the laboratory systematically dissects the apoptotic signaling pathways both upstream and downstream of the mitochondria to identify the specific alterations that render cancer cells unresponsive to drug treatment and aims to elucidate the apoptotic signaling pathways most critical for the development and maintenance of acquired chemoresistance. One of the laboratory's current research focuses is to elucidate the molecular mechanisms of acquired resistance to the FDA-approved HER2 inhibitor lapatinib in HER2-positive breast cancer cells.
For a complete listing of publications, visit PubMed.