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Miguel N. Rivera, MD
Assistant Professor of Pathology, Harvard Medical SchoolAssistant in Pathology, Massachusetts General HospitalAssociate Member, Broad Institute
Molecular Pathology UnitMassachusetts General Hospital149 13th Street, 6th FloorCharlestown, MA 02129Phone: 617-726-6257Email: firstname.lastname@example.org
Pediatric tumors are often driven by mutations in genes that directly control gene expression programs such as transcription factors and chromatin regulators. Our laboratory uses genomic technologies to identify abnormal gene regulation patterns in tumors and to analyze critical oncogenic pathways in several systems. Given that the mechanisms that drive pediatric tumors are poorly understood at present, we anticipate that our work will point to new therapies for these diseases.
Read more about the Rivera Lab from the Center for Cancer Research Annual Report.
Gaylor Boulay, PhD Angela VolorioAlexandra Cauderay Shruthi Rengarajan Nathan GiacconeMiguel N. Rivera, MD
Epigenomic approaches to identify critical pathways in cancer
We are using genomic technologies to identify abnormal gene regulation patterns in pediatric cancer. In particular, genome-wide chromatin profiling, which combines chromatin immunoprecipitation and high-throughput sequencing, is a powerful technology that can identify active and repressed states in the genome based on patterns of histone modifications. Our work using this technology has shown that Wilms tumors exhibit chromatin features typical of stem cells and that patterns of chromatin remodeling can reveal the mechanisms of action of aberrant transcriptional regulators such as the EWS-FLI1 fusion protein in Ewing sarcoma and the transcription factor OTX2 in medulloblastoma. We are now using a combination of biochemical and genomic tools to continue our analysis of these and other key transcriptional pathways in pediatric cancer.
Role of the WTX gene family in cancer and development
Wilms tumor, the most common pediatric kidney cancer, arises from kidney-specific stem cells and is a prime example of the connection between cancer and development. Through mapping genomic deletions in Wilms tumor we identified WTX, an X-linked tumor suppressor gene commonly inactivated in this disease and recently implicated in colon cancer. WTX is the founding member of a new protein family (FAM123) and our work using a conditional knockout mouse model has shown that it regulates mesenchymal stem cells in several organs, including kidneys, bones and fat. We are now studying the function of WTX and related proteins using several in vitro and in vivo model systems.
Cancer-Specific Retargeting of BAF Complexes by a Prion-like Domain. Boulay G, Sandoval GJ, Riggi N, Iyer S, Buisson R, Naigles B, Awad ME, Rengarajan S, Volorio A, McBride MJ, Broye LC, Zou L, Stamenkovic I, Kadoch C, Rivera MN. Cell 2017 Sep 21;171(1):1-16.
OTX2 activity at distal regulatory elements shapes the chromatin landscape of Group 3 medulloblastoma. Boulay G, Awad M, Riggi N, Archer T, Boonseng W, Rosetti N, Naigles B, Volorio A, Iyer S, Kim J, Mesirov JP, Tamayo P, Pomeroy SL, Aryee MJ, Rivera MN. Cancer Discovery 2017 Mar 7(3):288-301.
EWS-FLI1 utilizes divergent chromatin remodeling mechanisms to directly activate or repress enhancer elements in Ewing sarcoma. Riggi N, Knoechel B, Gillespie SM, Rheinbay E, Boulay G, Suvà ML, Rossetti NE, Boonseng WE, Oksuz O, Cook EB, Formey A, Patel A, Gymrek M, Thapar V, Deshpande V, Ting DT, Hornicek FJ, Nielsen GP, Stamenkovic I, Aryee MJ, Bernstein BE, Rivera MN. Cancer Cell. 2014 Nov 10;26(5):668-81.
Wilms tumor chromatin profiles highlight stem cell properties and a renal developmental network. Aiden AP, Rivera MN, Rheinbay E, Ku M, Coffman EJ, Truong TT, Vargas SO, Lander ES, Haber DA, Bernstein BE. Cell Stem Cell. 2010 Jun 4;6(6):591-602.
An X chromosome gene, WTX, is commonly inactivated in Wilms tumor. Rivera MN, Kim WJ, Wells J, Driscoll DR, Brannigan BW, Han M, Kim JC, Feinberg AP, Gerald WL, Vargas SO, Chin L, Iafrate AJ, Bell DW, Haber DA. Science. 2007 Feb 2;315(5812):642-5.
Massachusetts General Hospital
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