Ping Dou

Biography

Dr. Dou's commitment to cancer research is centered on targeted therapies, drug discovery, natural products, and chemoprevention. The main objective in his laboratory is aimed at discovering molecular targets of natural and synthetic small molecules in pre-clinical studies, followed by validation in targeted clinical trials. His laboratory is one of the first to report that proteasome inhibitors rapidly induce tumor cell apoptosis, selectively activate the cell death program in oncogene-transformed, but not normal or untransformed cells, and are able to trigger apoptotic death in human cancer cells that are resistant to various anticancer agents. His laboratory with collaborators has also shown that some tea polyphenols, curcumin, DIM, medicinal compounds and metal complexes potently and specifically inhibit the chymotrypsin-like activity of the proteasome in vitro and in vivo. They have also found that (i) novel epigallocatechin gallate (EGCG) analogs and BR-DIM activate AMP-activated protein kinase (AMPK) pathway, target cancer stem cells and induce apoptosis; (ii) novel EGCG and curcumin analogs increase efficacy of bortezomib; (iii) transcriptional activation of breast cancer-associated gene 2 (BCA2) by estrogen receptor. Most recently they have found that metformin treatment of breast cancer cells induces the E3 ligase BCA2 protein expression that then feedback inhibits the induced AMPK activation. Their discovery of this novel BCA2-AMPK regulatory pathway explains well why patients have various responses to metformin therapies and suggests that metformin therapy with a BCA2 inhibitor may be a more effective breast cancer treatment strategy than metformin alone. The successful completion of this project will significantly improve understanding of the molecular mechanisms of clinical metformin efficacy, help interpret the existing clinical data about various metformin efficacies in different cancer patients, and provide a scientific basis for designing a rationalized metformin-based breast cancer prevention clinical trial.

Research Interest

Oncology, Pharmacology and Pathology