Co-Founder and Director:
Gennadi V. Glinsky, M.D., Ph.D.
Head, Translational and Functional Genomics Laboratory
Genlight Technolgy Corporation
Director, Translational & Functional Genomics Program
Genlight Technolgy Corporation
In May of 2014 Dr. Glinsky joined Faculty at the Institute of Engineering in Medicine (IEM) at the University of California, San Diego. Please visit the site to learn more.
Consulting Professor, Stanford University School of Medicine
Member, The Rockefeller University Adjunct Faculty
Visiting Professor, Sanford-Burnham Medical Research Institute (2011-2014)
Professor, Adjunct, Department of Surgery, Division of Urology, Albany Medical College
Professor, Adjunct, Department of Pathology and Laboratory Medicine, Albany Medical College
Main Research Interests and Major Scientific Fields:
Unique to human genomic regulatory sequences. RNA-guided diagnostics and therapeutics for next-generation individualized nanomedicine. Role of gene deserts, intergenic and intronic long-range enhancers, and small non-coding RNA pathways in cancer and other common human disorders.
Hi-C, TCC, and ChIA-PET analyses of the structural basis of genome-wide long-range functional interactions between intergenic disease-associated SNPs, lncRNAs, microRNAs, and transcripts derived from protein-coding genetic loci. Sequence homology profiling and expression analysis of small non-coding RNAs. Genomics of stemness phenotype and cancer metastasis. Role of stemness pathways in development of therapy-resistance and death-from-cancer phenotype of human cancer. Prognostic and diagnostic genetic tests for individualized target-tailored therapy of human disorders. Transcriptional aberrations during progression of human prostate and breast cancer. Apoptosis and metastasis. Molecular basis of resistance toward apoptosis of 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. Clinically-relevant biological markers of human cancer. Aberrant glycosylation in cancer. Glycobiospecific targeting of cancer. Structural characterization of the biomolecular interactions. Structure-function relationships of the glycoconjugates. Biochemistry and biology of nonenzymatic glycosylation of proteins in diabetes and cancer.
939 Coast Blvd, Suite 4M, La Jolla, CA 92037
Dr. Glinsky has over 30 years of experience and expertise in conducting cancer research using clinically relevant animal models of cancer metastasis, molecular biology, molecular imaging, and oncogenomics. Dr. Glinsky and colleagues have made groundbreaking observations in the area of genomics of common human diseases highlighting critically important role of intergenic non-protein-coding regions of human genomes in predisposition to multiple common disorders. Discovery and functional characterization of small non-coding trans-regulatory RNAs (transRNAs) containing intergenic disease-associated SNPs (snpRNAs), which were recently isolated and sequenced in Dr. Glinsky’s laboratory, challenges nearly exclusive, dominant position of the protein-centric dogma in genetic and molecular biology of physiology and pathology of H. sapiens. Dr. Glinsky is a major contributor to the invention, development, and practical implementation of the concept and principles of the “signature approach” to genome-wide microarray-based gene expression analysis. His recent work in the mouse/human cross-species translational genomics filed has made a major impact on discovery of the genetic link between “stemness” phenotypes and therapy-resistance phenotypes of human cancer. He invented the gene expression-based cancer therapy outcome predictor (CTOP) algorithm and carry-out the retrospective clinical validation of the multi-signature CTOP algorithm for four distinct types of epithelial tumors, including breast, prostate, lung, and ovarian cancers. Dr. Glinsky’s lab was at the origin of discoveries of the links between metastatic behavior and apoptosis-resistance phenotypes and telomerase/telomere-dependent mechanisms of resistance to apoptosis. Dr. Glinsky is one of the originators of the concept of anti-adhesion cancer therapy and is a leading specialist in the field of anti-adhesion therapy of metastatic disease. He is a major contributor to the discovery and preclinical development of a novel family of low molecular weight therapeutic compounds named antimetastatic synthetic glycoamines.
Traditional and long-standing interest of this laboratory is the investigation of cell biological, genetic, and molecular mechanisms underlying the phenotype of metastatic cancer with an emphasis on development of clinically relevant companion diagnostic and prognostic tests 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 in the area of the functional genomics of tumor progression and metastasis. In particular, this research program 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. Concurrently we are developing a related research program focusing on functional genomics and proteomics of human breast cancer progression and metastasis. This research is rapidly expanding into 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 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.
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.
We are continuing several 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 21 major human disorders, including 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 sixteen major human disorders.