Professor, Department of Pathology
Adjunct Professor, Pharmacology and ToxicologyTumor Cell Biology Program
MD, Biophysics, Second Moscow State Medical Institute, Moscow, USSR, 1981
PhD, Immunology, Institute of Tuberculosis, Moscow, USSR, 1989
Postdoc, 1991-94, University of Virginia, Charlottesville, VA
Postdoc, 1994-98, Northwestern University, Chicago, IL
2500 N State St., Suite G758
Jackson, MS 39216
Phone: (601) 815-6072
Identification of "bone metastatic signature" a few years ago allowed us to focus on selected candidate genes that hold promise as potential biomarkers and therapeutic targets of bone metastases. We have shown that one of these genes, metastasis-associated protein 1 (MTA1), which is a chromatin modifier, plays a critical role in prostate cancer progression by inhibiting apoptosis and promoting angiogenesis. We also have evidence that MTA1 can serve as an independent prognostic marker for aggressive prostate cancer, particularly in African American men.
Currently, we aim to understand MTA1-mediated genetic and epigenetic mechanisms in prostate cancer pathogenesis. We have shown that MTA1/ HDAC1/2 inactivate tumor suppressors p53 and PTEN leading to inhibition of apoptosis and promotion of pAkt-mediated survival pathways. Using small interfering RNA technology, we have found that the loss of MTA1 decreases the proliferative and metastatic potential of cells in vitro and in vivo, particularly through mechanisms associated with the induction of apoptosis and reduction of angiogenesis. In addition, the role of MTA1 in the epithelial-to-mesenchymal transition and radioresistance in prostate cancer is of interest. While working with already identified target candidates such as pAkt, HIF1-α, and e-cadherin, we are interested in identifying new potential MTA1-associated high-risk biomarkers. At the moment, we are analyzing our MTA1 ChIP-Seq data which identified about 33,000 direct MTA1-DNA binding peaks in the mouse genome.
Another major interest is potential chemopreventive and therapeutic efficacy of dietary agents such as resveratrol and its potent analogues in prostate cancer. We found that resveratrol/analogues inhibit MTA1 and rescue acetylation of tumor suppressors' p53 and PTEN. The novel MTA1-mediated epigenetic mechanism of action of dietary compounds is under intensive investigation with preclinical testing in my laboratory.
We are also interested in another epigenetic regulatory network, which is represented by microRNAs and Epi-microRNAs.
2500 North State Street
Jackson, MS 39216
General Information: 601-984-1000
Patient Appointments: 888-815-2005