Michael H. Peters, Ph.D.
Research program member: Developmental Therapeutics
601 W. Main St.
Richmond, VA 23298
Professor, Chemical and Life Science Engineering, College of Engineering
PhD, Ohio State University (1981)
MS, Ohio State University (1979)
My research focuses on anti-apoptotic inhibitors in cancer. An estimated 500,000 women die each year from breast cancer world-wide. Chemotherapeutic agents in the treatment of breast cancer are based on the particular cancer cell type, such as drugs that specifically target the HER2 protein for HER2-positive breast cancers. Breast cancers can develop chemo-resistance through the blocking of cell death pathways, such as the blocking of apoptotic pathways (anti-apoptotic behavior). We have developed a potential, novel peptide inhibitor to Bcl-2 associated anthanogen (BAG-1), which is associated with anti-apoptotic pathways prevalent in a variety of cancer cell types including, breast cancers. An all-atom, dominant energy landscape mapping of BAG-1 to its HSP-70/HSC-70 (heat shock protein 70 and its conjugate) binding partner identified a helical peptide segment from the binding domain of HSC-70. Experimental kinetic binding studies demonstrated that this peptide binds to BAG-1 in the pico-molar range. Subsequently, we augmented the helical peptide with a poly-arginine CPP (cell penetrating peptide) and demonstrated dose-dependent increases in apoptosis in a number of hematological cancer cell lines and primary patient AML cells. BAG-1 could be a critical target in multimode chemotherapeutic approaches aimed at breast cancer. In fact, BAG-1 inhibition via knockdown studies was recently demonstrated to synergistically enhance the effects of trastuzumab in HER2 positive breast cancer cell lines.
Apoptosis,Bioinformatics,Biomarkers,Chemical biology,Drug discovery,Molecular medicine,Proteomics,Signal transduction,Targeted therapies