Dr. Ronald A. DePinho
The University of Texas MD Anderson Cancer Center
Department of Cancer Biology
Our research program has focused on elucidation of the genetic basis of complex human diseases of the aged and the translation of such knowledge into clinical endpoints. A major focus has been to determine the mechanistic bases for the intimate link between epithelial carcinogenesis and advancing age, the most significant risk factor for cancer in humans. Our investigation of the molecular circuitry and biology of the aging and cancer process has encompassed determining how genotoxic stress (particularly telomeres and p53), mitochondrial biogenesis and function, and stem cell dynamics conspire to drive organismal decline and provoke age-associated diseases as cancer and neurodegeneration (Sahin et al., Nature 2011; Jaskelioff et al., Nature 2011; Sahin and DePinho, Nat Rev Mol Cell Biol 2012) . In addition, our research program has sought to generate a more comprehensive understanding of highly lethal cancers with the goal of driving clinical progress in these challenging diseases. In this regard, we have focused principally on Glioblastoma (Zheng et al., Cancer Cell 2010; Chen et al., Genes Dev 2012), Pancreatic Cancer (Ying et al., Cancer Discov 2011; Ying et al., Cell 2012), and more recently, Prostate Cancer (Ding et al., Nature 2011; Ding et al., Cell 2012). Our general approach has been to organize multi-disciplinary, multi-technology, multi-institutional, basic-translational teams working towards securing a comprehensive view of driver events, understand how such genetic aberrations govern tumor biology, determine co-extinction strategies for more durable therapeutic responses, create faithful mouse models of the disease to formulate and test clinical path hypothesis and to facilitate the development of diagnostic and therapeutic agents (Muller et al., Nature 2012; Hu et al, Cell 2012). In particular, the challenge of cancer’s complexity on the genomic and biological levels has motivated us to exploit the experimental merits of highly refined genetically engineered mouse models of cancer. Illustrative examples have included our continued use of (i) genome unstable murine cancer models as filters to identify many new cancer genes via comparative oncogenomics with multi-dimensional human datasets of the TCGA, (ii) inducible model systems to validate genetic elements in tumor maintenance and to enable screens for discovery of novel targets that may be surrogates of undruggable targets, (iii) genetically faithful mouse models and comparative proteomics to identify early detection biomarkers markers, and (iv) integrated analysis of mouse and human cancer biospecimens to identify molecular determinants of disease progression, particularly prostate cancer. It will be our goal to integrate these research efforts into the rich fabric of its formidable translational programs in (i) prevention through our knowledge of how aging pathways might govern risk in MDACC’s prevention program and its rich databases, (ii) early disease detection via integrating our comparative proteomics approach with MDACC’s mature experimental pathology and imaging infrastructure, (iii) evidenced-based management of early stage disease enabled by our functional-genomics approach to identify biomarkers driving lethal cancer progression and MDACC’s established CLIA operations in experimental pathology, and (iv) our systematic deep biology efforts designed to identify and understand unprecedented targets for enlistment into the newly established Institute for Applied Cancer Science and the Institute for Personalized Cancer Therapy.
Office: MDA FCT 20.5000 (Unit 1491)
M.D. - Albert Einstein College of Medicine - 1981