Photo of Sridhar Ramaswamy,  MD

Sridhar Ramaswamy, MD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 643-3140
Fax: (617) 643-3170


sridhar@mgh.harvard.edu

Sridhar Ramaswamy, MD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Associate Professor, Medicine, Harvard Medical School
  • Tucker Gosnell Investigator, Cancer Center, Massachusetts General Hospital
  • Associate Professor of Medicine, Cancer Center, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

We are working to identify mechanisms that enable cancers to metastasize, but then lay dormant at distant sites, only to recur late after apparently curative treatment. We combine molecular and cell biology, imaging, bioengineering, and systems approaches to identify pathways that regulate cancer cell invasion, metastasis, and dormancy. We are also using advanced genomics, computation, and statistical data-mining to: 1) identify diagnostic, prognostic, and drug response genes across a spectrum of cancer types; and 2) discover molecular pathways in cancer and stem cells that regulate proliferation, invasion, differentiation, and resistance to therapeutics.

Publications

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  • Faber AC, Farago AF, Costa C, Dastur A, Gomez-Caraballo M, Robbins R, Wagner BL, Rideout WM, Jakubik CT, Ham J, Edelman EJ, Ebi H, Yeo AT, Hata AN, Song Y, Patel NU, March RJ, Tam AT, Milano RJ, Boisvert JL, Hicks MA, Elmiligy S, Malstrom SE, Rivera MN, Harada H, Windle BE, Ramaswamy S, Benes CH, Jacks T, Engelman JA. Assessment of ABT-263 activity across a cancer cell line collection leads to a potent combination therapy for small-cell lung cancer. Proc Natl Acad Sci U S A 2015; 112:E1288-96. PubMed
  • Javaid S, Zhang J, Smolen GA, Yu M, Wittner BS, Singh A, Arora KS, Madden MW, Desai R, Zubrowski MJ, Schott BJ, Ting DT, Stott SL, Toner M, Maheswaran S, Shioda T, Ramaswamy S, Haber DA. MAPK7 regulates EMT Features and Modulates the Generation of CTCs. Mol Cancer Res 2015. PubMed
  • Dey-Guha I, Alves CP, Yeh AC, Salony, Sole X, Darp R, Ramaswamy S. A mechanism for asymmetric cell division resulting in proliferative asynchronicity. Mol Cancer Res 2015; 13:223-30. PubMed
  • Niederst MJ, Sequist LV, Poirier JT, Mermel CH, Lockerman EL, Garcia AR, Katayama R, Costa C, Ross KN, Moran T, Howe E, Fulton LE, Mulvey HE, Bernardo LA, Mohamoud F, Miyoshi N, VanderLaan PA, Costa DB, Jänne PA, Borger DR, Ramaswamy S, Shioda T, Iafrate AJ, Getz G, Rudin CM, Mino-Kenudson M, Engelman JA. RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer. Nat Commun 2015; 6:6377. PubMed
  • Kwiatkowski N, Zhang T, Rahl PB, Abraham BJ, Reddy J, Ficarro SB, Dastur A, Amzallag A, Ramaswamy S, Tesar B, Jenkins CE, Hannett NM, McMillin D, Sanda T, Sim T, Kim ND, Look T, Mitsiades CS, Weng AP, Brown JR, Benes CH, Marto JA, Young RA, Gray NS. Targeting transcription regulation in cancer with a covalent CDK7 inhibitor. Nature 2014. PubMed
  • Korenjak M, Kwon E, Morris RT, Anderssen E, Amzallag A, Ramaswamy S, Dyson NJ. dREAM co-operates with insulator-binding proteins and regulates expression at divergently paired genes. Nucleic Acids Res 2014. PubMed
  • Yu M, Bardia A, Aceto N, Bersani F, Madden MW, Donaldson MC, Desai R, Zhu H, Comaills V, Zheng Z, Wittner BS, Stojanov P, Brachtel E, Sgroi D, Kapur R, Shioda T, Ting DT, Ramaswamy S, Getz G, Iafrate AJ, Benes C, Toner M, Maheswaran S, Haber DA. Cancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility. Science 2014; 345:216-20. PubMed
  • Saha SK, Parachoniak CA, Ghanta KS, Fitamant J, Ross KN, Najem MS, Gurumurthy S, Akbay EA, Sia D, Cornella H, Miltiadous O, Walesky C, Deshpande V, Zhu AX, Hezel AF, Yen KE, Straley KS, Travins J, Popovici-Muller J, Gliser C, Ferrone CR, Apte U, Llovet JM, Wong KK, Ramaswamy S, Bardeesy N. Mutant IDH inhibits HNF-4留 to block hepatocyte differentiation and promote biliary cancer. Nature 2014. PubMed
  • Luo X, Mitra D, Sullivan RJ, Wittner BS, Kimura AM, Pan S, Hoang MP, Brannigan BW, Lawrence DP, Flaherty KT, Sequist LV, McMahon M, Bosenberg MW, Stott SL, Ting DT, Ramaswamy S, Toner M, Fisher DE, Maheswaran S, Haber DA. Isolation and molecular characterization of circulating melanoma cells. Cell Rep 2014. PubMed
  • Foudi A, Kramer DJ, Qin J, Ye D, Behlich AS, Mordecai S, Preffer FI, Amzallag A, Ramaswamy S, Hochedlinger K, Orkin SH, Hock H. Distinct, strict requirements for Gfi-1b in adult bone marrow red cell and platelet generation. J Exp Med 2014. PubMed
  • McMullin RP, Wittner BS, Yang C, Denton-Schneider BR, Hicks D, Singavarapu R, Moulis S, Lee J, Akbari MR, Narod SA, Aldape KD, Steeg PS, Ramaswamy S, Sgroi DC. A BRCA1 deficient-like signature is enriched in breast cancer brain metastases and predicts DNA damage-induced poly (ADP-ribose) polymerase inhibitor sensitivity. Breast Cancer Res 2014; 16:R25. PubMed
  • Faber AC, Coffee EM, Costa C, Dastur A, Ebi H, Hata AN, Yeo AT, Edelman EJ, Song Y, Tam AT, Boisvert JL, Milano RJ, Roper J, Kodack DP, Jain RK, Corcoran RB, Rivera MN, Ramaswamy S, Hung KE, Benes CH, Engelman JA. mTOR inhibition specifically sensitizes colorectal cancers with KRAS or BRAF mutations to BCL-2/BCL-XL inhibition by suppressing MCL-1. 2014; 4:42-52. PubMed
  • Silberman DM, Ross K, Sande PH, Kubota S, Ramaswamy S, Apte RS, Mostoslavsky R. SIRT6 Is Required for Normal Retinal Function. PLoS ONE 2014; 9:e98831. PubMed
  • Javaid S, Zhang J, Anderssen E, Black JC, Wittner BS, Tajima K, Ting DT, Smolen GA, Zubrowski M, Desai R, Maheswaran S, Ramaswamy S, Whetstine JR, Haber DA. Dynamic chromatin modification sustains epithelial-mesenchymal transition following inducible expression of Snail-1. Cell Rep 2013; 5:1679-89. PubMed
  • Liu M, Roth A, Yu M, Morris R, Bersani F, Rivera MN, Lu J, Shioda T, Vasudevan S, Ramaswamy S, Maheswaran S, Diederichs S, Haber DA. The IGF2 intronic miR-483 selectively enhances transcription from IGF2 fetal promoters and enhances tumorigenesis. Genes Dev 2013; 27:2543-8. PubMed
  • Chen EY, Dobrinski KP, Brown KH, Clagg R, Edelman E, Ignatius MS, Chen JY, Brockmann J, Nielsen GP, Ramaswamy S, Keller C, Lee C, Langenau DM. Cross-species array comparative genomic hybridization identifies novel oncogenic events in zebrafish and human embryonal rhabdomyosarcoma. PLoS Genet. 2013; 9:e1003727. PubMed
  • Keliher EJ, Reiner T, Earley S, Klubnick J, Tassa C, Lee AJ, Ramaswamy S, Bardeesy N, Hanahan D, Depinho RA, Castro CM, Weissleder R. Targeting cathepsin E in pancreatic cancer by a small molecule allows in vivo detection. Neoplasia 2013; 15:684-93. PubMed
  • Desmet CJ, Gallenne T, Prieur A, Reyal F, Visser NL, Wittner BS, Smit MA, Geiger TR, Laoukili J, Iskit S, Rodenko B, Zwart W, Evers B, Horlings H, Ajouaou A, Zevenhoven J, van Vliet M, Ramaswamy S, Wessels LF, Peeper DS. Identification of a pharmacologically tractable Fra-1/ADORA2B axis promoting breast cancer metastasis. Proc Natl Acad Sci U S A 2013; 110:5139-44. PubMed
  • Yu M, Bardia A, Wittner BS, Stott SL, Smas ME, Ting DT, Isakoff SJ, Ciciliano JC, Wells MN, Shah AM, Concannon KF, Donaldson MC, Sequist LV, Brachtel E, Sgroi D, Baselga J, Ramaswamy S, Toner M, Haber DA, Maheswaran S. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science 2013; 339:580-4. PubMed
  • Yang W, Soares J, Greninger P, Edelman EJ, Lightfoot H, Forbes S, Bindal N, Beare D, Smith JA, Thompson IR, Ramaswamy S, Futreal PA, Haber DA, Stratton MR, Benes C, McDermott U, Garnett MJ. Genomics of Drug Sensitivity in Cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells. Nucleic Acids Res 2012; 41:D955-61. PubMed
  • Polo JM, Anderssen E, Walsh RM, Schwarz BA, Nefzger CM, Lim SM, Borkent M, Apostolou E, Alaei S, Cloutier J, Bar-Nur O, Cheloufi S, Stadtfeld M, Figueroa ME, Robinton D, Natesan S, Melnick A, Zhu J, Ramaswamy S, Hochedlinger K. A molecular roadmap of reprogramming somatic cells into iPS cells. Cell 2012; 151:1617-32. PubMed
  • Jalili A, Wagner C, Pashenkov M, Pathria G, Mertz KD, Widlund HR, Lupien M, Brunet JP, Golub TR, Stingl G, Fisher DE, Ramaswamy S, Wagner SN. Dual Suppression of the Cyclin-Dependent Kinase Inhibitors CDKN2C and CDKN1A in Human Melanoma. Journal of the National Cancer Institute 2012; 104:1673-9. PubMed
  • Korenjak M, Anderssen E, Ramaswamy S, Whetstine JR, Dyson NJ. RBF Binding to both Canonical E2F Targets and Noncanonical Targets Depends on Functional dE2F/dDP Complexes. Mol Cell Biol 2012; 32:4375-87. PubMed
  • Miyamoto DT, Lee RJ, Stott SL, Ting DT, Wittner BS, Ulman M, Smas ME, Lord JB, Brannigan BW, Trautwein J, Bander NH, Wu CL, Sequist LV, Smith MR, Ramaswamy S, Toner M, Maheswaran S, Haber DA. Androgen receptor signaling in circulating tumor cells as a marker of hormonally responsive prostate cancer. 2012; 2:995-1003. PubMed
  • Qin J, Whyte WA, Anderssen E, Apostolou E, Chen HH, Akbarian S, Bronson RT, Hochedlinger K, Ramaswamy S, Young RA, Hock H. The polycomb group protein L3mbtl2 assembles an atypical PRC1-family complex that is essential in pluripotent stem cells and early development. Cell Stem Cell 2012; 11:319-32. PubMed
  • Yu M, Ting DT, Stott SL, Wittner BS, Ozsolak F, Paul S, Ciciliano JC, Smas ME, Winokur D, Gilman AJ, Ulman MJ, Xega K, Contino G, Alagesan B, Brannigan BW, Milos PM, Ryan DP, Sequist LV, Bardeesy N, Ramaswamy S, Toner M, Maheswaran S, Haber DA. RNA sequencing of pancreatic circulating tumour cells implicates WNT signalling in metastasis. Nature 2012; 487:510-3. PubMed
  • Garnett MJ, Edelman EJ, Heidorn SJ, Greenman CD, Dastur A, Lau KW, Greninger P, Thompson IR, Luo X, Soares J, Liu Q, Iorio F, Surdez D, Chen L, Milano RJ, Bignell GR, Tam AT, Davies H, Stevenson JA, Barthorpe S, Lutz SR, Kogera F, Lawrence K, McLaren-Douglas A, Mitropoulos X, Mironenko T, Thi H, Richardson L, Zhou W, Jewitt F, Zhang T, O'Brien P, Boisvert JL, Price S, Hur W, Yang W, Deng X, Butler A, Choi HG, Chang JW, Baselga J, Stamenkovic I, Engelman JA, Sharma SV, Delattre O, Saez-Rodriguez J, Gray NS, Settleman J, Futreal PA, Haber DA, Stratton MR, Ramaswamy S, McDermott U, Benes CH. Systematic identification of genomic markers of drug sensitivity in cancer cells. Nature 2012; 483:570-5. PubMed
  • Dey-Guha I, Wolfer A, Yeh AC, G Albeck J, Darp R, Leon E, Wulfkuhle J, Petricoin EF, Wittner BS, Ramaswamy S. Asymmetric cancer cell division regulated by AKT. Proc Natl Acad Sci U S A 2011; 108:12845-50. PubMed
  • Sharma SV, Lee DY, Li B, Quinlan MP, Takahashi F, Maheswaran S, McDermott U, Azizian N, Zou L, Fischbach MA, Wong KK, Brandstetter K, Wittner B, Ramaswamy S, Classon M, Settleman J. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell 2010; 141:69-80. PubMed
  • Wolfer A, Wittner BS, Irimia D, Flavin RJ, Lupien M, Gunawardane RN, Meyer CA, Lightcap ES, Tamayo P, Mesirov JP, Liu XS, Shioda T, Toner M, Loda M, Brown M, Brugge JS, Ramaswamy S. MYC regulation of a "poor-prognosis" metastatic cancer cell state. Proc Natl Acad Sci U S A 2010; 107:3698-703. PubMed
  • Ramaswamy S. Rational design of cancer-drug combinations. N Engl J Med 2007; 357:299-300. PubMed
  • Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 2004; 117:927-39. PubMed
  • Ramaswamy S. Translating cancer genomics into clinical oncology. N Engl J Med 2004; 350:1814-6. PubMed
  • Lamb J, Ramaswamy S, Ford HL, Contreras B, Martinez RV, Kittrell FS, Zahnow CA, Patterson N, Golub TR, Ewen ME. A mechanism of cyclin D1 action encoded in the patterns of gene expression in human cancer. Cell 2003; 114:323-34. PubMed
  • Ramaswamy S, Perou CM. DNA microarrays in breast cancer: the promise of personalised medicine. Lancet 2003; 361:1576-7. PubMed
  • Ramaswamy S, Ross KN, Lander ES, Golub TR. A molecular signature of metastasis in primary solid tumors. Nat Genet 2002; 33:49-54. PubMed
  • Ramaswamy S, Golub TR. DNA microarrays in clinical oncology. J Clin Oncol 2002; 20:1932-41. PubMed
  • Ramaswamy S, Tamayo P, Rifkin R, Mukherjee S, Yeang CH, Angelo M, Ladd C, Reich M, Latulippe E, Mesirov JP, Poggio T, Gerald W, Loda M, Lander ES, Golub TR. Multiclass cancer diagnosis using tumor gene expression signatures. Proc Natl Acad Sci U S A 2001; 98:15149-54. PubMed
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