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Karmanos scientist receives two-year grant from National Cancer Institute, Institutes of Health

Gen Sheng Wu, Ph.D., associate professor in the Department of Oncology at Karmanos and WSU SOM, has received a two-year, $363,660 grant (R21CA178111) from the National Institutes of Health and the National Cancer Institute for his project, “A novel role for PARP1 in regulation of autophagy.”

Dr. Wu is collaborating with John Reiners, Ph.D., professor at the Institute of Environmental Health Sciences, part of the Eugene Applebaum College of Pharmacy & Health Sciences at WSU.

Many standard cancer treatments, including chemotherapy drugs and radiation, cause DNA damage of rapidly dividing cancer cells, leading to apoptotic cell death, Dr. Wu’s research explains. PARP1 has been shown to help repair damage caused by chemotherapy drugs and radiation and may cause tumor cells to survive and grow. This can cause treatment failure. Therefore, PARP1 has been identified as an attractive target for improvement of current treatments.

A number of PARP inhibitors have been developed, and preclinical studies suggest that standard therapies combined with PARP inhibitors may be more effective than standard therapies alone. Studies suggest that PARP inhibitors could be effective as single agents against tumors with inherent DNA repair defects, in particular, breast and ovarian cancers that carry mutations in the BRCA1 and BRCA2 genes.

Dr. Wu’s current grant will investigate a novel role for PARP1, and the link between PARP1 and autophagy, a cellular process that sometimes leads to cell death. Specifically, this grant will study how PARP1 interacts with the core autophagy machinery to affect autophagy induction. Many anticancer agents cause cellular damage that is counteracted by a parallel induction of autophagy. Both PARP1 inhibitors and autophagy inhibitors often enhance the cytotoxicities of chemotherapeutic drugs and have advanced to use in clinical trials. An understanding of their interaction may facilitate the design of approaches for more effective treatment of cancer.

We congratulate Dr. Wu on his grant!

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