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INVESTIGATOR PROFILES |
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SENIOR SCIENTIST DIRECTOR PROFESSOR, ADJUNCT ADJUNCT PROFESSOR CONTACT |
Gennadi V. Glinsky, M.D., Ph.D.Research FocusTraditional and long-standing interest of this laboratory is the investigation of cell biological, genetic, and molecular mechanisms underlying the phenotypic base of metastatic human cancer with an emphasis on development of clinically relevant companion diagnostic/prognostic assays and structure/function-guided design and pre-clinical evaluation of anti-adhesive and anti-metastatic small molecule therapeutics. One of the main aspects of our research program is focused in the area of the functional genomics of tumor progression and metastasis. In particular, this research is aimed at molecular definition of the transcriptome of metastatic prostate cancer with an emphasis on identification of molecular and genetic targets amenable for diagnostic and therapeutic applications. 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 a set of emerging follow-up projects targeting specific cancer-related clinically-relevant phenotypes and regulatory pathways such as “stemness” pathways and “death-from-cancer” phenotypes. 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 personalized, target-tailored clinical management of human prostate cancer. Most recently we initiated an array of novel research projects aimed at investigation of the role of small non-coding RNA (sncRNA) pathways in human diseases. We are exploring the structural-functional relationships of disease-associated SNPs, microRNAs, and transcripts derived from the protein-coding genes in the genomic contexts related to the 17 major human disorders (Alzheimer’s disease (AD); bipolar disease (BD); rheumatoid arthritis (RA); coronary artery disease (CAD); Crohn's disease (CD); type 1 diabetes (T1D); type 2 diabetes (T2D); hypertension (HT); ankylosing spondylitis (AS); Graves' disease (autoimmune thyroid disease; AITD); multiple sclerosis (MS); breast cancer (BC); prostate cancer (PC); systemic lupus erythematosus (SLE); vitiligo-associated multiple autoimmune disease (VIT); Huntington’s disease (HD), and ulcerative colitis (UC). This research is enabled by multiple independent genome-wide association studies of up to 451,012 combined samples including 194,258 disease cases and 256,754 controls. Our analysis reveals a systematic primary sequence homology/complementarity-driven pattern of associations between disease-linked SNPs, microRNAs and protein-coding mRNAs defined here as a human disease phenocode. Disease phenocode hypothesis postulates that in trans cumulative effects on phenotypes of disease-associated SNPs are mediated by the SNP sequence-bearing RNAs interfering with the biogenesis and/or functions of microRNAs. We utilize this approach to draw SNP-guided microRNA (MirMaps) maps of major human diseases and define a consensus disease phenocode for fifteen major human disorders. Our long term objective is to combine past and present interests and expertise to develop a comprehensive (both experimental and translational) targeted therapeutics and personalized disease-management programs 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 pro-drugs and structure-guided development of small molecule drug candidates. Main Research Interests and Major Scientific Fields:Role of small non-coding RNA pathways in human diseases. Structural-functional relationships between disease-associated SNPs, microRNAs, and transcripts derived from protein-coding genetic loci. Sequence homology profiling and expression analysis of small non-coding RNAs. 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. Selected Publications (View)
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