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Sridhar Ramaswamy, MDAssociate Professor of MedicineHarvard Medical School
Tucker Gosnell InvestigatorAttending PhysicianMassachusetts General Hospital Cancer CenterMassachusetts General Hospital Center for Regenerative Medicine
Associate MemberBroad Institute of Harvard and MITHarvard Stem Cell Institute
Research SummaryOur laboratory is working to understand how human cancer genomes regulate solid tumor growth, metastasis, dormancy, and drug response. Our major goal is to use insights from our studies to develop entirely new strategies for the personalized diagnosis and treatment of cancer.
Sridhar Ramaswamy, MDPrincipal Investigator
Ramaswamy Lab Photo Gallery
Asymmetric Cancer Cell Division
We have a major interest in understanding how human cancer genomes regulate solid tumor progression. We are particularly interested in defining transcriptional networks that regulate metastasis, dormancy, and drug response. Several years ago, we and others found that multi-gene transcriptional signatures are expressed by a majority of malignant cells within tumors that are destined to metastasize. These studies spurred the development and deployment of widely-used gene signature-based clinical diagnostics for the diagnosis and risk-stratification of cancer patients with different tumor types. We recently found that virtually all of these “poor prognosis” signatures indirectly reflect the activity within tumors of the MYC transcription factor. Moreover, we found that MYC specifically regulates cancer cell invasion and metastasis (apart from it’s well studied roles in proliferation and survival), suggesting that quantitative increases in MYC activity may ultimately cause solid tumor metastasis. Since MYC is arguably the most common human oncogene, understanding precisely how MYC regulates metastasis might suggest new strategies for therapeutically targeting advanced cancers. Current projects include 1) DNA-seq, RNA-seq, and ChIP-seq profiling to comprehensively define the metastasis-related MYC transcriptional state; and 2) functional studies probing this MYC network in vitro and in vivo.
Research PositionsPostdoctoral Research Fellow Cancer BiologyA Postdoctoral Research Fellow position is available to study human solid tumor metastasis, drug resistance, and/or dormancy. The candidate must have recently received a PhD or MD PhD degree in the biological sciences, and be highly motivated and well versed in basic molecular biology, cell biology, and biochemical techniques with special interests in transcriptional regulation, epigenetics, stem cell biology, and/or live cell imaging. The Fellow will have simultaneous academic appointments at the Massachusetts General Hospital, Harvard Medical School, and the Broad Institute. The laboratory provides a rich intellectual environment within a group of highly collaborative investigators, with full integration into the large research communities of the Massachusetts General Hospital, Harvard University, the Broad Institute, and the Harvard Stem Cell Institute.
Interested candidates should e-mail a brief cover letter and CV to:Sridhar Ramaswamy, MDMassachusetts General Hospital Cancer Center/Harvard Medical School 185 Cambridge Street, Boston, MA 02114
Staff Scientist Computational Biology & Bioinformatics
A Staff Scientist position is available for a highly qualified expert in Computational Biology and Bioinformatics in the Center for Computational Discovery at the Massachusetts General Hospital Cancer Center and Harvard Medical School. The individual will join a highly motivated, collaborative, and multi-disciplinary team using high-throughput approaches to answer applied and fundamental questions in cancer biology and medicine. He or she will provide bioinformatics and computational biology expertise for analyzing a significant next generation sequencing (NGS) data stream (e.g., DNA-seq, RNA-seq, ChIP-seq, methylation, etc.) and collaborate across the Mass General Cancer Center with different research groups on related projects. We seek a highly motivated and independent thinker with a PhD or MS in Mathematics, Statistics, Computer Science, or Bioinformatics/Computational Biology, significant familiarity with statistical computing and NGS tools, strong interpersonal skills, and a track record of collaborative work in a multidisciplinary research environment.
Interested candidates should e-mail a brief cover letter and CV to:Sridhar Ramaswamy, MD ORBen Wittner, PhD Center for Computational DiscoveryMassachusetts General Hospital Cancer Center/Harvard Medical School 185 Cambridge Street Boston, MA 02114
Yu M, Bardia A, Wittner BS, Stott SL, Smas ME, Ting DT, Isakoff S, Ciciliano JC, Wells, MN, Shah AM, Concannon K, 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; 339:580-84. PMID: 23372014
Polo JM, Anderssen E, Walsh RM, Schwarz B, Borkent M, Apostolou E, Stadtfeld M, Figueroa ME, Robinton D, Natesan S, Melnick A, Ramaswamy S, Hochedlinger K. A molecular roadmap of reprogramming somatic cells into iPS cells. Cell 2012; 151:1617-1632. PMID: 23260147
Garnett MJ, Edelman EJ, Heidorn SJ, Greenman C, Dastur A, Lau KW, Greninger P, Thompson IR, Luo XN, Soares J, Liu Q, Iorio F, Milano RJ, Bignell G, Tam AT, Davies H, Stevenson JA, Barthorpe A, Lutz SR, McLaren-Douglas A, Mitropoulos X, Mironenko T, Thi H, Richardson L, Zhou W, Jewitt F, Zhang T, O’Brien P, Price S, Hur W, Yang W, Deng X, Butler A, Choi HG, Chang JW, Baselga J, Stamenkovich I, Engelman J, Sharma SV, Saez-Rodriguez J, Gray NS, Settleman J, Futreal PA, Haber DA, Stratton MR, Ramaswamy S, McDermott U, Benes C. A systematic screen identifies genomic biomarkers of drug sensitivity in cancer cells. Nature 2012; 483:570-577. PMID: 22460902
Dey-Guha I, Wolfer A, Yeh AC, Albeck JG, Darp R, Leon E, Wulfkuhle J, Petricoin EF, Wittner BS, Ramaswamy S. Asymmetric cancer cell division regulated by AKT. Proc Natl Acad Sci USA 2011; 108:12845-12850. PMID: 21757645
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. PMID: 20371346
Wolfer A, Wittner BS, Irimia D, Flavin RJ, Lupien M, Gunawardane RN, Meyer CA, Lightcap E, 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 USA 2010; 107:3608-3703. PMID: 20133671
Ramaswamy S, Ross KN, Lander ES, Golub TR. A molecular signature of metastasis in primary solid tumors. Nature Genetics 2003; 33:49-54. PMID: 12469122
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. Multi-class cancer diagnosis using tumor gene expression signatures. Proc Natl Acad Sci USA 2001; 98:15149-15154. PMID: 11742071
View a list of additional publications by researchers at the Ramaswamy Laboratory
Richard B. Simches Research Center
Directions to the Ramaswamy Lab.
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