COM4S_M.TTF

Research Focus

Traditional and long-standing interest of this laboratory is the investigation of cell biological and molecular mechanisms underlying the phenotypic base of metastatic human cancer with an emphasis on structure/function-guided design and pre-clinical development of anti-adhesive and anti-metastatic small molecule therapeutics. The anti-bacterial therapeutics research program was initiated recently with support from NIH and combined the functional proteomics and combinatorial peptide phage display library approaches to develop novel anti-bacterial D-peptide-based compounds that are designed to specifically target protein-protein interactions essential for assembly and function of the bacterial RNA polymerase. Recently, our research program expanded in the area of the functional genomics of tumor progression and metastasis. This research is supported by a five-year RO1 from the NCI to conduct research aimed at molecular definition of the transcriptome of metastatic prostate cancer. Currently we are developing a related research program focusing on functional genomics and proteomics of human breast cancer progression and metastasis. This is rapidly expanding into set of emerging follow-up projects targeting specific cancer-related phenotypes and regulatory pathways. Molecular and genetic analysis of the apoptosis rescue pathways distinguishing localized and metastatic prostate cancer is one example of such projects and will be an important milestone in defining novel diagnostic, prognostic, and therapeutic targets highly relevant to the clinical management of human prostate cancer.

Our long term objective is to combine past and present interests and expertise to develop a comprehensive experimental therapeutics program comprising a combination of high throughput high resolution capabilities of the functional genomics and proteomics at the target identification and validation stage with combinatorial chemistry approaches for identification of peptide-based prodrugs and structure-guided development of small molecule drug candidates.

Main Research Interests and Major Scientific Fields: Transcriptional aberrations during progression of human prostate and breast cancer. Apoptosis and metastasis. Molecular basis of resistance toward apoptosis in metastatic cancer cells. Molecular mechanisms of cancer metastasis and antimetastatic drug design. Telomere homeostasis and programmed cell death. Biochemistry of cell-cell recognition and adhesion. Biological markers of human cancer. Aberrant glycosylation in cancer. Glycobiospecific targeting of cancer. Structural characterization of the biomolecules. Structure-function relationships of the glycoconjugates. Biochemistry and biology of nonenzymatic glycosylation of proteins in diabetes and cancer. Common genetic and molecular mechanism(s) of E.coli resistance to starvation, UV-radiation, and oxidative stress. Transcriptional regulation in prokaryotes. Subunit-subunit interactions during RNAP assembly. Antibacterial drug design.

Selected Publications

• Glinsky GV, Integration of HapMap-based SNP pattern analysis and gene expression profiling reveals common SNP profiles for cancer therapy outcome predictor genes. Cell Cycle. 2006 Nov;5(22):2613-25. Epub 2006 Nov 15
• Glinsky GV, Berezovskaya O, Glinskii AB. Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. J Clin Invest. 2005 Jun;115(6):1503-21. PMID: 15931389 [PubMed – in process]
• Berezovskaya O, Schimmer AD, Glinskii AB, Pinilla C, Hoffman RM, Reed JC, Glinsky GV. Increased expression of apoptosis inhibitor protein XIAP contributes to anoikis resistance of circulating human prostate cancer metastasis precursor cells. Cancer Res 2005; 65: (6). March 15, 2005
• Glinsky GV, Higashiyama T, Glinskii AB. Classification of human breast cancer using gene expression profiling as a component of the survival predictor algorithm. Clin Cancer Res. 2004 Apr 1;10(7):2272-83.
• Glinsky GV, Glinskii AB, Stephenson AJ, Hoffman RM, Gerald WL. Gene expression profiling predicts clinical outcome of prostate cancer. J Clin Invest. 2004 Mar;113(6):913-23.
• Schimmer AD, Welsh K, Pinilla C, Wang Z, Krajewska M, Bonneau MJ, Pedersen IM, Kitada S, Scott FL, Bailly-Maitre B, Glinsky G, Scudiero D, Sausville E, Salvesen G, Nefzi A, Ostresh JM, Houghten RA, Reed JC. Small-molecule antagonists of apoptosis suppressor XIAP exhibit broad antitumor activity. Cancer Cell. 2004 Jan;5(1):25-35.