Vijaya Ramesh, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 724-9733
Fax: (617) 726-5736


ramesh@helix.mgh.harvard.edu

Vijaya Ramesh, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Associate Professor, Neurology, Harvard Medical School
  • Assistant in Genetics (Neurology), Molecular Genetics Unit, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

My laboratory focuses on understanding the pathophysiology of inherited cancer syndromes such as Neurofibromatosis 2(NF2) and Tuberous Sclerosis type 1 and type 2 (TSC1 and TSC2). The NF2 protein merlin belongs to a family of proteins that are known to connect the plasma membrane proteins to the actin cytoskeleton. One aspect of our work involves understanding the role of merlin in cellular signaling to the actin cytoskeleton. We have recently identified NHE-RF, a regulatory protein for many ion channels as an interacting protein for merlin. NHE-RF appears to function as a key adaptor protein involved in many signaling pathways and our efforts are to define the role of NHE-RF in cell proliferation.

Tuberous sclerosis results from mutations in either of the two genes TSC1 and TSC2 and functions of the protein products hamartin and tuberin respectively are largely unknown. We have generated valuable antibodies for these proteins and defined their subcellular pattern of expression in kidney, one of the affected organs in TSC. Work is in progress to isolate, characterize other proteins that interact with these two proteins. The ultimate goal is to define the physiological functions of these proteins and how their absence results in this multisystem disorder.

Publications

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  • Prabhakar S, Zhang X, Goto J, Han S, Lai C, Bronson R, Sena-Esteves M, Ramesh V, Stemmer-Rachamimov A, Kwiatkowski DJ, Breakefield XO. Survival benefit and phenotypic improvement by hamartin gene therapy in a tuberous sclerosis mouse brain model. Neurobiol Dis 2015; 82:22-31. PubMed
  • Widemann BC, Acosta MT, Ammoun S, Belzberg AJ, Bernards A, Blakeley J, Bretscher A, Cichowski K, Clapp DW, Dombi E, Evans GD, Ferner R, Fernandez-Valle C, Fisher MJ, Giovannini M, Gutmann DH, Hanemann CO, Hennigan R, Huson S, Ingram D, Kissil J, Korf BR, Legius E, Packer RJ, McClatchey AI, McCormick F, North K, Pehrsson M, Plotkin SR, Ramesh V, Ratner N, Schirmer S, Sherman L, Schorry E, Stevenson D, Stewart DR, Ullrich N, Bakker AC, Morrison H. CTF meeting 2012: Translation of the basic understanding of the biology and genetics of NF1, NF2, and schwannomatosis toward the development of effective therapies. Am J Med Genet A 2014; 164A:563-78. PubMed
  • Han S, Kim S, Bahl S, Li L, Burande CF, Smith N, James M, Beauchamp RL, Bhide P, DiAntonio A, Ramesh V. The E3 ubiquitin ligase protein associated with Myc (Pam) regulates mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling in vivo through N- and C-terminal domains. J Biol Chem 2012; 287:30063-72. PubMed
  • Huson SM, Acosta MT, Belzberg AJ, Bernards A, Chernoff J, Cichowski K, Gareth Evans D, Ferner RE, Giovannini M, Korf BR, Listernick R, North KN, Packer RJ, Parada LF, Peltonen J, Ramesh V, Reilly KM, Risner JW, Schorry EK, Upadhyaya M, Viskochil DH, Zhu Y, Hunter-Schaedle K, Giancotti FG. Back to the future: proceedings from the 2010 NF Conference. Am J Med Genet A 2011; 155:307-21. PubMed
  • Kissil JL, Blakeley JO, Ferner RE, Huson SM, Kalamarides M, Mautner VF, McCormick F, Morrison H, Packer R, Ramesh V, Ratner N, Rauen KA, Stevenson DA, Hunter-Schaedle K, North K. What's new in neurofibromatosis? Proceedings from the 2009 NF Conference: new frontiers. Am J Med Genet A 2010; 152A:269-83. PubMed
  • James MF,Han S,Polizzano C,Plotkin SR,Manning BD,Stemmer-Rachamimov AO,Gusella JF,Ramesh V. NF2/Merlin is a Novel Negative Regulator of mTOR Complex 1 and Activation of mTORC1 is Associated with Meningioma and Schwannoma Growth. Mol Cell Biol 2009; 29:4250-61. PubMed
  • Han S,Polizzano C,Nielsen GP,Hornicek FJ,Rosenberg AE,Ramesh V. Aberrant hyperactivation of akt and Mammalian target of rapamycin complex 1 signaling in sporadic chordomas. Clin Cancer Res 2009; 15:1940-6. PubMed
  • Shen Y, Nunes F, Stemmer-Rachamimov A, James M, Mohapatra G, Plotkin S, Betensky RA, Engler DA, Roy J, Ramesh V, Gusella JF. Genomic profiling distinguishes familial multiple and sporadic multiple meningiomas. BMC Med Genomics 2009; 2:42. PubMed
  • Ehninger D,Han S,Shilyansky C,Zhou Y,Li W,Kwiatkowski DJ,Ramesh V,Silva AJ. Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis. Nat Med 2008; 14:843-8. PubMed
  • Han S, Witt RM, Santos TM, Polizzano C, Sabatini BL, Ramesh V. Pam (Protein associated with Myc) functions as an E3 Ubiquitin ligase and regulates TSC/mTOR signaling. Cell Signal 2008; 20:1084-91. PubMed
  • James MF, Lelke JM, Maccollin M, Plotkin SR, Stemmer-Rachamimov AO, Ramesh V, Gusella JF. Modeling NF2 with human arachnoidal and meningioma cell culture systems: NF2 silencing reflects the benign character of tumor growth. Neurobiol Dis 2007; 29:278-92. PubMed
  • Beyer KS, Beauchamp RL, Lee MF, Gusella JF, Naar AM, Ramesh V. Mediator subunit MED28 (Magicin) is a repressor of smooth muscle cell differentiation. J Biol Chem 2007; 282:32152-7. PubMed
  • Lee MF, Beauchamp RL, Beyer KS, Gusella JF, Ramesh V. Magicin associates with the Src-family kinases and is phosphorylated upon CD3 stimulation. Biochem Biophys Res Commun 2006; 348:826-31. PubMed
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