Photo of Vijaya Ramesh, PhD

Vijaya Ramesh, PhD

Massachusetts General Hospital

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


ramesh@helix.mgh.harvard.edu

Photo of Vijaya Ramesh, PhD

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


ramesh@helix.mgh.harvard.edu

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Vijaya Ramesh, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

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

DF/HCC PROGRAM AFFILIATION

Research Abstract

Ramesh laboratory has been investigating the pathophysiology of Neurofibromatosis 2 (NF2) and Tuberous Sclerosis Complex (TSC) for almost two decades. Her lab employs molecular, genetic, cell signaling and biochemistry techniques in disease-relevant human cells to discover pathways and mechanisms of pathophysiology in NF2 and TSC. The work on NF2 in human arachnoidal and meningioma cells discovered that NF2 protein merlin is a novel negative regulator of mTORC1 signaling. This work has been translated into clinical trials with RAD001 for NF2 and sporadic meningiomas. Ramesh lab has also established CRISPR-Cas genome editing technology in human arachanoidal cells, Schwann cells and iPSCs and has used this technique to create/correct mutations in NF1, NF2, TSC1 and TSC2 generating isogenic sets of human lines for drug screening and other research efforts.

Publications from Harvard Catalyst Profiles

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  • Hsieh AL, Bi WL, Ramesh V, Brastianos PK, Plotkin SR. Evolving concepts in meningioma management in the era of genomics. Cancer 2024. PubMed
  • Bhattacharyya S, Oblinger JL, Beauchamp RL, Kosa L, Robert F, Plotkin SR, Chang LS, Ramesh V. Preclinical evaluation of the third-generation, bi-steric mechanistic target of rapamycin complex 1-selective inhibitor RMC-6272 in -deficient models. 2024; 6:vdae024. PubMed
  • Bhattacharyya S, Oblinger JL, Beauchamp RL, Yin Z, Erdin S, Koundinya P, Ware AD, Ferrer M, Jordan JT, Plotkin SR, Xu L, Chang LS, Ramesh V. Proteasomal pathway inhibition as a potential therapy for NF2-associated meningioma and schwannoma. 2023. PubMed
  • Jordan JT, Orr CC, Thalheimer RD, Cambillo JV, Beauchamp RL, Shaikh G, Muzikansky A, Stemmer-Rachamimov A, Giovannini M, Kalamarides M, Barker FG, Ramesh V, Plotkin SR. Prospective phase II trial of the dual mTORC1/2 inhibitor vistusertib for progressive or symptomatic meningiomas in persons with neurofibromatosis 2. 2023; 5:vdad041. PubMed
  • Prabhakar S, Beauchamp RL, Cheah PS, Yoshinaga A, Haidar EA, Lule S, Mani G, Maalouf K, Stemmer-Rachamimov A, Jung DH, Welling DB, Giovannini M, Plotkin SR, Maguire CA, Ramesh V, Breakefield XO. Gene replacement therapy in a schwannoma mouse model of neurofibromatosis type 2. Mol Ther Methods Clin Dev 2022; 26:169-180. PubMed
  • St Pierre R, Collings CK, Samé Guerra DD, Widmer CJ, Bolonduro O, Mashtalir N, Sankar A, Liang Y, Bi WL, Gerkes EH, Ramesh V, Qi J, Smith MJ, Meredith DM, Kadoch C. SMARCE1 deficiency generates a targetable mSWI/SNF dependency in clear cell meningioma. Nat Genet 2022; 54:861-873. PubMed
  • Chang LS, Oblinger JL, Smith AE, Ferrer M, Angus SP, Hawley E, Petrilli AM, Beauchamp RL, Riecken LB, Erdin S, Poi M, Huang J, Bessler WK, Zhang X, Guha R, Thomas C, Burns SS, Gilbert TSK, Jiang L, Li X, Lu Q, Yuan J, He Y, Dixon SAH, Masters A, Jones DR, Yates CW, Haggarty SJ, La Rosa S, Welling DB, Stemmer-Rachamimov AO, Plotkin SR, Gusella JF, Guinney J, Morrison H, Ramesh V, Fernandez-Valle C, Johnson GL, Blakeley JO, Clapp DW, . Brigatinib causes tumor shrinkage in both NF2-deficient meningioma and schwannoma through inhibition of multiple tyrosine kinases but not ALK. PLoS ONE 2021; 16:e0252048. PubMed
  • Cheah PS, Prabhakar S, Yellen D, Beauchamp RL, Zhang X, Kasamatsu S, Bronson RT, Thiele EA, Kwiatkowski DJ, Stemmer-Rachamimov A, György B, Ling KH, Kaneki M, Tannous BA, Ramesh V, Maguire CA, Breakefield XO. Gene therapy for tuberous sclerosis complex type 2 in a mouse model by delivery of AAV9 encoding a condensed form of tuberin. Sci Adv 2021. PubMed
  • Beauchamp RL, Erdin S, Witt L, Jordan JT, Plotkin SR, Gusella JF, Ramesh V. mTOR kinase inhibition disrupts neuregulin 1-ERBB3 autocrine signaling and sensitizes NF2-deficient meningioma cellular models to IGF1R inhibition. J Biol Chem 2020; 296:100157. PubMed
  • Beauchamp RL, Erdin S, Witt L, Jordan JT, Plotkin SR, Gusella JF, Ramesh V. mTOR kinase inhibition disrupts neuregulin 1-ERBB3 autocrine signaling and sensitizes -deficient meningioma cellular models to IGF1R inhibition. J Biol Chem 2020. PubMed
  • Sagers JE, Beauchamp RL, Zhang Y, Vasilijic S, Wu L, DeSouza P, Seist R, Zhou W, Xu L, Ramesh V, Stankovic KM. Combination therapy with mTOR kinase inhibitor and dasatinib as a novel therapeutic strategy for vestibular schwannoma. Sci Rep 2020; 10:4211. PubMed
  • Angus SP, Oblinger JL, Stuhlmiller TJ, DeSouza PA, Beauchamp RL, Witt L, Chen X, Jordan JT, Gilbert TSK, Stemmer-Rachamimov A, Gusella JF, Plotkin SR, Haggarty SJ, Chang LS, Johnson GL, Ramesh V, . EPH receptor signaling as a novel therapeutic target in NF2-deficient meningioma. 2018; 20:1185-1196. PubMed
  • Jordan JT, Smith MJ, Walker JA, Erdin S, Talkowski ME, Merker VL, Ramesh V, Cai W, Harris GJ, Bredella MA, Seijo M, Suuberg A, Gusella JF, Plotkin SR. Pain correlates with germline mutation in schwannomatosis. Medicine (Baltimore) 2018; 97:e9717. PubMed
  • , Allaway R, Angus SP, Beauchamp RL, Blakeley JO, Bott M, Burns SS, Carlstedt A, Chang LS, Chen X, Clapp DW, Desouza PA, Erdin S, Fernandez-Valle C, Guinney J, Gusella JF, Haggarty SJ, Johnson GL, La Rosa S, Morrison H, Petrilli AM, Plotkin SR, Pratap A, Ramesh V, Sciaky N, Stemmer-Rachamimov A, Stuhlmiller TJ, Talkowski ME, Welling DB, Yates CW, Zawistowski JS, Zhao WN. Traditional and systems biology based drug discovery for the rare tumor syndrome neurofibromatosis type 2. PLoS ONE 2018; 13:e0197350. PubMed
  • Blakeley JO, Bakker A, Barker A, Clapp W, Ferner R, Fisher MJ, Giovannini M, Gutmann DH, Karajannis MA, Kissil JL, Legius E, Lloyd AC, Packer RJ, Ramesh V, Riccardi VM, Stevenson DA, Ullrich NJ, Upadhyaya M, Stemmer-Rachamimov A. The path forward: 2015 International Children's Tumor Foundation conference on neurofibromatosis type 1, type 2, and schwannomatosis. Am J Med Genet A 2017; 173:1714-1721. PubMed
  • Nigim F, Esaki SI, Hood M, Lelic N, James MF, Ramesh V, Stemmer-Rachamimov A, Cahill DP, Brastianos PK, Rabkin SD, Martuza RL, Wakimoto H. A new patient-derived orthotopic malignant meningioma model treated with oncolytic herpes simplex virus. 2016. PubMed
  • 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
  • Beauchamp RL, James MF, DeSouza PA, Wagh V, Zhao WN, Jordan JT, Stemmer-Rachamimov A, Plotkin SR, Gusella JF, Haggarty SJ, Ramesh V. A high-throughput kinome screen reveals serum/glucocorticoid-regulated kinase 1 as a therapeutic target for NF2-deficient meningiomas. 2015; 6:16981-97. PubMed
  • Li L, Walsh RM, Wagh V, James MF, Beauchamp RL, Chang YS, Gusella JF, Hochedlinger K, Ramesh V. Mediator Subunit Med28 Is Essential for Mouse Peri-Implantation Development and Pluripotency. PLoS ONE 2015; 10:e0140192. 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 2008; 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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DF/HCC members that share similar concepts* with Vijaya Ramesh, PhD but have yet to coauthor a publication with this researcher.

* Concepts are MeSH terms, automatically derived from member publications

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