个人简介

B.Sc. Honors (Bio Chemistry), 1993-1996, University of Delhi, Delhi, India M.Sc. Biochemistry, 1996-1998; Hamdard University, Delhi, India Ph.D., 2000-2005, University of North Carolina, Chapel Hill, NC (Kerry S Bloom Ph.D.) National fellowship for Research and Training from Govt. of India, CSIR, 1998; Abstract selected for short talk, FASEB Summer Research conference (yeast chromosome segregation), 2000; Keystone Symposia Award (Molecular Biology of the Vasculature), 2006; Best Poster Award. Pharmacology Retreat and Symposium, Duke University, 2008; Abstract selected for short talk (Keystone meeting, TGF-β in disease), 2008; Career Development Award for Ovarian Cancer Research (Dept. of Defense), 2009-2012; Tilberis Scholar Award, Ovarian Cancer Research Fund, 2013-2016.

研究领域

Biochemistry

Key Words: Growth factor-receptor signaling mechanisms and signal transduction pathways, Epithelial and Tumor cell biology including Cell survival mechanisms, Cell migration and invasion biology, Cell adhesion and Mechanobiology. The overall goal of the lab is two fold: 1) Discover the molecular and cellular basis of cancer initiation and metastasis as controlled by growth factors. Specific emphasis is laid on the TGF-β superfamily of growth factors, their receptors, co-receptors and their crosstalk with the integrin family of cell adhesion receptors in cancer. 2) To translate these discoveries into a source of novel therapeutic targets as well as strategies to reduce cancer incidence and improve/predict patient outcomes. The transforming growth factor-β (TGF-β) superfamily of growth factors, including the TGF-β ligands, the Bone morphogenetic proteins (BMPs), Activins and Inhibin have physiological roles in regulation of growth, cell differentiation and apoptosis in a cell and context-specific manner. TGFβ family ligands induce phenotypic changes in cancer cells including altered morphology, adhesion, motility and invasive behavior via a signal transduction cascade illustrated in Figure 1 and play dichotomous roles in cancer progression switching from tumor suppressors to tumor promoters. Understanding the mechanism of this dichotomy of TGF-β superfamily function remains a fundamental problem in the cancer biology field and affects our ability to target these pathways in various pathologies. Three core research areas include: • Role of integrins in regulating TGF-β’s effects on carcinogenesis. We have recently determined that TGF-β coreceptors traffic with integrins that impacts their subcellular distribution in cells and cancer tissues. Emphasis will be laid on the intersection of TGF-β and BMP signaling and integrin biology in the context of gynecological cancers, ovarian and breast cancer. • BMP’s are emerging as regulators of breast and ovarian physiology. The aim is to determine the contribution of BMP’s in cell survival in ovarian and breast cancer. • Defining the intersection between growth factor/biochemical signals and mechanical signals received by cells as the extracellular matrix environment changes in disease. Specifically, the lab investigates how changes in the TGF-β pathways during epithelial to mesenchymal transition may act as a mechanism utilized by cancers to evade mechanical cues to impact cancer cell behavior in breast and ovarian cancer.

近期论文

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Erik H Knelson, Angela L Gaviglio, Alok K Tewari, Michael B Armstrong, Karthikeyan Mythreye, and Gerard C Blobe*. Type III TGF-beta receptor promotes FGF2-mediated neuronal differentiation in neuroblastoma. J Clin Invest. 2013 Nov 1;123(11):4786-98 (* equal contribution senior author). Sun Young Oh, Erik. H. Knelson, G.C. Blobe, K. Mythreye. The type III TGFβ receptor regulates filopodia formation via a Cdc42-mediated IRSp53-N-WASP interaction in epithelial cells. Biochem J. 2013 Aug 15;454 (1):79-89. doi: 10.1042/BJ20121701. Tian H, Mythreye K, Golzio C, Katsanis N, Blobe GC. Endoglin mediates fibronectin/α5β1 integrin and TGF-β pathway crosstalk in endothelial cells. EMBO J. 2012 Aug 31. doi: 10.1038/emboj.2012.246. [Epub ahead of print]. Christopher C. Pan, Jeffrey C. Bloodworth, Karthikeyan Mythreye and Nam Y. Lee Endoglin Inhibits ERK-induced c-Myc and Cyclin D1 Expression to Impede Endothelial Cell Proliferation. Biochem Biophys Res Commun. 2012 Aug 3;424(3):620-3. Epub 2012 Jul 10. K. Mythreye, E. Knelson, C.E.Gatza , M.L. Gatza and G.C Blobe TβRIII/β-arrestin2 regulates integrin α5β1 trafficking function, and localization in epithelial cells Oncogene. 2013 Mar 14;32(11):1416-27]. V Swaminathan, K Mythreye, Timothy E. O'Brien, A. Berchuck , G C. Blobe, R Superfine. Mechanical stiffness grades metastatic potential in patient tumor cells and in cancer cell lines. (equal first author) Cancer Research 2011 Aug 1;71(15):5075-80. Epub 2011 Jun 3. Lambert KE, Huang H, Mythreye K, Blobe GC. The type III transforming growth factor-β receptor inhibits proliferation, migration, and adhesion in human myeloma cells. Mol Biol Cell. 2011 Mar 16. Mythreye K and Blobe GC. The type III TGFbeta receptor regulates directional migration: new tricks for an old dog. Cell Cycle. 2009 Oct 1;8(19): 3069-70. Mythreye K and Blobe GC. Proteoglycan signaling co-receptors: roles in cell adhesion, migration and invasion. Cell Signal. 2009 Nov;21(11):1548-58. Mythreye K, Blobe GC. The type III TGF-beta receptor regulates epithelial and cancer cell migration through beta-arrestin2-mediated activation of Cdc42. Proc Natl Acad Sci U S A. 2009 May 19; 106(20): 8221-6.