|Title:||Assistant Professor / Biochemistry and Molecular Biology
|Department of Chemistry and Biochemistry|
Office: GSRC 309
Lab: GSRC 324, 803-777-6323
Lab 2: GSRC 325
Lab 3: GSRC 335A
Mythreye Karthikeyan Group Website
B.Sc., 1996, University of Delhi
M.Sc., 1998, Hamdard University
Ph.D., 2005, University of North Carolina
Honors and Awards
Liz Tilberis Scholar Award, Ovarian Cancer Research Fund, 2013-2016; Career Development Award, Ovarian Cancer Research (Department of Defense), 2009-2012.
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
The overall goal of the lab is to: 1) Discover the molecular and cellular basis of
cancer growth and metastasis. Emphasis is laid on the TGF-β family of growth
factors, receptors, co-receptors and their crosstalk with pathways including
the Wnt/ β-catenin pathway and the integrin family of cell adhesion receptors
2) To translate these discoveries into a source of novel therapeutic targets and
Overview: The transforming growth factor-β (TGF-β) family 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, switching from tumor suppressors to tumor promoters. Defining
context specific outcomes of TGF-β signaling will improve ability to target
these pathways in various pathologies.
Core research areas:
• Transcriptional Regulation of Cell Survival and Metastasis in Cancer
• Impact of Post Translational modifications of cell surface receptors in
• Paracrine regulation of tumor angiogenesis
• Investigating intersections between biochemical signals and mechanical
signals received by cells as the extracellular matrix environment
changes in disease.
Mechanistic studies are conducted in cell line models of cancer either in two
dimension (Figure 2), or in specialized three dimensional organotype culture
models (Figure 3).
Defined mechanisms are translated into preclinical work using small molecule
inhibitors, antibodies and chemotherapeutic agents in xenograft models and
transgenic mice to determine invivo impact.
TGF-β triggers rapid fibrillogenesis via a novel TβRII-dependent fibronectin-trafficking mechanism. Varadaraj A, Jenkins LM, Singh P, Chanda A, Snider J, Lee NY, Amsalem-Zafran AR, Ehrlich M, Henis YI, Mythreye K. Mol Biol Cell. 2017 May 1;28(9):1195-1207. Epub 2017 Mar 15. DOI: 10.1091/mbc.E16-08-0601.
Altering the Proteoglycan State of Transforming Growth Factor β Type III Receptor
(TβRIII)/Betaglycan Modulates Canonical Wnt/β-Catenin Signaling.Jenkins LM, Singh
P, Varadaraj A, Lee NY, Shah S, Flores HV, O'Connell K, MythreyeK. J Biol Chem. 2016 Dec 2;291(49):25716-25728. Epub 2016 Oct 26.
Kumar S, Pan CC, Shah N, Wheeler SE, Hoyt KR, Hempel N, Mythreye K, Lee NY. Activation
of Mitofusin2 by Smad2-RIN1 Complex during Mitochondrial Fusion. Mol Cell. 2016 May 19;62(4):520-31. Epub 2016 May 12.
Varadaraj A, Patel P, Serrao A, Bandyopadhay T, Lee NY, Jazaeri AA, Huang Z, Murphy
SK, Mythreye K. Epigenetic regulation of GDF2 suppresses anoikis in ovarian and breast epithelia
Neoplasia. 2015 Nov 17; (11):826-38.
Osborne, L.; Li, G. Z.; O Brian, E. T.; How, T.; Blobe, G. C.; Superfine, R.; K. Mythreye. TGF-β Regulates LARG and GEF-H1 During EMT to Impact Stiffening Response to Force
and Cell Invasion. Mol. Biol. Cell. 2014, 25:22, 3528 - 3540.