Photo of Esther Rheinbay,  PhD

Esther Rheinbay, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 726-5634


erheinbay@mgh.harvard.edu

Esther Rheinbay, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Assistant Professor, Medicine, Harvard Medical School
  • Principal Investigator, Mass General Cancer Center, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Most known genomic drivers of cancer are in coding genes, affecting the encoded protein’s interaction with other proteins, DNA or biological compounds. Recent advances in DNA sequencing technology have made it possible to study non-coding regions that regulate these protein-coding genes. Several cancer drivers have been identified and characterized in these regulatory regions, however, this genomic territory remains relatively unexplored in human tumors. The Rheinbay laboratory concentrates on identifying and functionally characterizing these non-coding drivers in the sequences of tumor whole genomes and epigenomes through development of novel analysis strategies and collaborations with experimental investigators.

We are also interested in tumors, especially breast cancers, for which no known protein-coding driver alterations have been found. In the age of targeted therapy, these tumors pose a special challenge in that they leave few treatment options for patients beyond conventional chemotherapy. We believe that finding novel genomic and epigenomic, protein-coding and regulatory therapeutic targets in these tumors will have significant clinical implications.

Publications

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  • Ouyang J, Yadav T, Zhang JM, Yang H, Rheinbay E, Guo H, Haber DA, Lan L, Zou L. RNA transcripts stimulate homologous recombination by forming DR-loops. Nature 2021. PubMed
  • Carrot-Zhang J, Yao X, Devarakonda S, Deshpande A, Damrauer JS, Silva TC, Wong CK, Choi HY, Felau I, Robertson AG, Castro MAA, Bao L, Rheinbay E, Liu EM, Trieu T, Haan D, Yau C, Hinoue T, Liu Y, Shapira O, Kumar K, Mungall KL, Zhang H, Lee JJ, Berger A, Gao GF, Zhitomirsky B, Liang WW, Zhou M, Moorthi S, Berger AH, Collisson EA, Zody MC, Ding L, Cherniack AD, Getz G, Elemento O, Benz CC, Stuart J, Zenklusen JC, Beroukhim R, Chang JC, Campbell JD, Hayes DN, Yang L, Laird PW, Weinstein JN, Kwiatkowski DJ, Tsao MS, Travis WD, Khurana E, Berman BP, Hoadley KA, Robine N, , Meyerson M, Govindan R, Imielinski M. Whole-genome characterization of lung adenocarcinomas lacking the RTK/RAS/RAF pathway. Cell Rep 2021; 34:108707. PubMed
  • Rheinbay E, Nielsen MM, Abascal F, Wala JA, Shapira O, Tiao G, Hornshøj H, Hess JM, Juul RI, Lin Z, Feuerbach L, Sabarinathan R, Madsen T, Kim J, Mularoni L, Shuai S, Lanzós A, Herrmann C, Maruvka YE, Shen C, Amin SB, Bandopadhayay P, Bertl J, Boroevich KA, Busanovich J, Carlevaro-Fita J, Chakravarty D, Chan CWY, Craft D, Dhingra P, Diamanti K, Fonseca NA, Gonzalez-Perez A, Guo Q, Hamilton MP, Haradhvala NJ, Hong C, Isaev K, Johnson TA, Juul M, Kahles A, Kahraman A, Kim Y, Komorowski J, Kumar K, Kumar S, Lee D, Lehmann KV, Li Y, Liu EM, Lochovsky L, Park K, Pich O, Roberts ND, Saksena G, Schumacher SE, Sidiropoulos N, Sieverling L, Sinnott-Armstrong N, Stewart C, Tamborero D, Tubio JMC, Umer HM, Uusküla-Reimand L, Wadelius C, Wadi L, Yao X, Zhang CZ, Zhang J, Haber JE, Hobolth A, Imielinski M, Kellis M, Lawrence MS, von Mering C, Nakagawa H, Raphael BJ, Rubin MA, Sander C, Stein LD, Stuart JM, Tsunoda T, Wheeler DA, Johnson R, Reimand J, Gerstein M, Khurana E, Campbell PJ, López-Bigas N, , , Weischenfeldt J, Beroukhim R, Martincorena I, Pedersen JS, Getz G, . Analyses of non-coding somatic drivers in 2,658 cancer whole genomes. Nature 2020; 578:102-111. PubMed
  • Whalley JP, Buchhalter I, Rheinbay E, Raine KM, Stobbe MD, Kleinheinz K, Werner J, Beltran S, Gut M, Hübschmann D, Hutter B, Livitz D, Perry MD, Rosenberg M, Saksena G, Trotta JR, Eils R, Gerhard DS, Campbell PJ, Schlesner M, Gut IG. Framework for quality assessment of whole genome cancer sequences. Nat Commun 2021; 11:5040. PubMed
  • Neftel C, Laffy J, Filbin MG, Hara T, Shore ME, Rahme GJ, Richman AR, Silverbush D, Shaw ML, Hebert CM, Dewitt J, Gritsch S, Perez EM, Gonzalez Castro LN, Lan X, Druck N, Rodman C, Dionne D, Kaplan A, Bertalan MS, Small J, Pelton K, Becker S, Bonal D, Nguyen QD, Servis RL, Fung JM, Mylvaganam R, Mayr L, Gojo J, Haberler C, Geyeregger R, Czech T, Slavc I, Nahed BV, Curry WT, Carter BS, Wakimoto H, Brastianos PK, Batchelor TT, Stemmer-Rachamimov A, Martinez-Lage M, Frosch MP, Stamenkovic I, Riggi N, Rheinbay E, Monje M, Rozenblatt-Rosen O, Cahill DP, Patel AP, Hunter T, Verma IM, Ligon KL, Louis DN, Regev A, Bernstein BE, Tirosh I, Suvà ML. An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma. Cell 2019; 178:835-849.e21. PubMed
  • Taylor-Weiner A, Stewart C, Giordano T, Miller M, Rosenberg M, Macbeth A, Lennon N, Rheinbay E, Landau DA, Wu CJ, Getz G. DeTiN: overcoming tumor-in-normal contamination. Nat Methods 2018; 15:531-534. PubMed
  • Maruvka YE, Mouw KW, Karlic R, Parasuraman P, Kamburov A, Polak P, Haradhvala NJ, Hess JM, Rheinbay E, Brody Y, Koren A, Braunstein LZ, D'Andrea A, Lawrence MS, Bass A, Bernards A, Michor F, Getz G. Analysis of somatic microsatellite indels identifies driver events in human tumors. Nat Biotechnol 2017. PubMed
  • Rheinbay E, Parasuraman P, Grimsby J, Tiao G, Engreitz JM, Kim J, Lawrence MS, Taylor-Weiner A, Rodriguez-Cuevas S, Rosenberg M, Hess J, Stewart C, Maruvka YE, Stojanov P, Cortes ML, Seepo S, Cibulskis C, Tracy A, Pugh TJ, Lee J, Zheng Z, Ellisen LW, Iafrate AJ, Boehm JS, Gabriel SB, Meyerson M, Golub TR, Baselga J, Hidalgo-Miranda A, Shioda T, Bernards A, Lander ES, Getz G. Recurrent and functional regulatory mutations in breast cancer. Nature 2017; 547:55-60. PubMed
  • Haradhvala NJ, Polak P, Stojanov P, Covington KR, Shinbrot E, Hess JM, Rheinbay E, Kim J, Maruvka YE, Braunstein LZ, Kamburov A, Hanawalt PC, Wheeler DA, Koren A, Lawrence MS, Getz G. Mutational Strand Asymmetries in Cancer Genomes Reveal Mechanisms of DNA Damage and Repair. Cell 2016; 164:538-49. PubMed
  • , Brat DJ, Verhaak RG, Aldape KD, Yung WK, Salama SR, Cooper LA, Rheinbay E, Miller CR, Vitucci M, Morozova O, Robertson AG, Noushmehr H, Laird PW, Cherniack AD, Akbani R, Huse JT, Ciriello G, Poisson LM, Barnholtz-Sloan JS, Berger MS, Brennan C, Colen RR, Colman H, Flanders AE, Giannini C, Grifford M, Iavarone A, Jain R, Joseph I, Kim J, Kasaian K, Mikkelsen T, Murray BA, O'Neill BP, Pachter L, Parsons DW, Sougnez C, Sulman EP, Vandenberg SR, Van Meir EG, von Deimling A, Zhang H, Crain D, Lau K, Mallery D, Morris S, Paulauskis J, Penny R, Shelton T, Sherman M, Yena P, Black A, Bowen J, Dicostanzo K, Gastier-Foster J, Leraas KM, Lichtenberg TM, Pierson CR, Ramirez NC, Taylor C, Weaver S, Wise L, Zmuda E, Davidsen T, Demchok JA, Eley G, Ferguson ML, Hutter CM, Mills Shaw KR, Ozenberger BA, Sheth M, Sofia HJ, Tarnuzzer R, Wang Z, Yang L, Zenklusen JC, Ayala B, Baboud J, Chudamani S, Jensen MA, Liu J, Pihl T, Raman R, Wan Y, Wu Y, Ally A, Auman JT, Balasundaram M, Balu S, Baylin SB, Beroukhim R, Bootwalla MS, Bowlby R, Bristow CA, Brooks D, Butterfield Y, Carlsen R, Carter S, Chin L, Chu A, Chuah E, Cibulskis K, Clarke A, Coetzee SG, Dhalla N, Fennell T, Fisher S, Gabriel S, Getz G, Gibbs R, Guin R, Hadjipanayis A, Hayes DN, Hinoue T, Hoadley K, Holt RA, Hoyle AP, Jefferys SR, Jones S, Jones CD, Kucherlapati R, Lai PH, Lander E, Lee S, Lichtenstein L, Ma Y, Maglinte DT, Mahadeshwar HS, Marra MA, Mayo M, Meng S, Meyerson ML, Mieczkowski PA, Moore RA, Mose LE, Mungall AJ, Pantazi A, Parfenov M, Park PJ, Parker JS, Perou CM, Protopopov A, Ren X, Roach J, Sabedot TS, Schein J, Schumacher SE, Seidman JG, Seth S, Shen H, Simons JV, Sipahimalani P, Soloway MG, Song X, Sun H, Tabak B, Tam A, Tan D, Tang J, Thiessen N, Triche T, Van Den Berg DJ, Veluvolu U, Waring S, Weisenberger DJ, Wilkerson MD, Wong T, Wu J, Xi L, Xu AW, Yang L, Zack TI, Zhang J, Aksoy BA, Arachchi H, Benz C, Bernard B, Carlin D, Cho J, DiCara D, Frazer S, Fuller GN, Gao J, Gehlenborg N, Haussler D, Heiman DI, Iype L, Jacobsen A, Ju Z, Katzman S, Kim H, Knijnenburg T, Kreisberg RB, Lawrence MS, Lee W, Leinonen K, Lin P, Ling S, Liu W, Liu Y, Liu Y, Lu Y, Mills G, Ng S, Noble MS, Paull E, Rao A, Reynolds S, Saksena G, Sanborn Z, Sander C, Schultz N, Senbabaoglu Y, Shen R, Shmulevich I, Sinha R, Stuart J, Sumer SO, Sun Y, Tasman N, Taylor BS, Voet D, Weinhold N, Weinstein JN, Yang D, Yoshihara K, Zheng S, Zhang W, Zou L, Abel T, Sadeghi S, Cohen ML, Eschbacher J, Hattab EM, Raghunathan A, Schniederjan MJ, Aziz D, Barnett G, Barrett W, Bigner DD, Boice L, Brewer C, Calatozzolo C, Campos B, Carlotti CG, Chan TA, Cuppini L, Curley E, Cuzzubbo S, Devine K, DiMeco F, Duell R, Elder JB, Fehrenbach A, Finocchiaro G, Friedman W, Fulop J, Gardner J, Hermes B, Herold-Mende C, Jungk C, Kendler A, Lehman NL, Lipp E, Liu O, Mandt R, McGraw M, Mclendon R, McPherson C, Neder L, Nguyen P, Noss A, Nunziata R, Ostrom QT, Palmer C, Perin A, Pollo B, Potapov A, Potapova O, Rathmell WK, Rotin D, Scarpace L, Schilero C, Senecal K, Shimmel K, Shurkhay V, Sifri S, Singh R, Sloan AE, Smolenski K, Staugaitis SM, Steele R, Thorne L, Tirapelli DP, Unterberg A, Vallurupalli M, Wang Y, Warnick R, Williams F, Wolinsky Y, Bell S, Rosenberg M, Stewart C, Huang F, Grimsby JL, Radenbaugh AJ, Zhang J. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas. N Engl J Med 2015; 372:2481-98. PubMed
  • Perry JA, Kiezun A, Tonzi P, Van Allen EM, Carter SL, Baca SC, Cowley GS, Bhatt AS, Rheinbay E, Pedamallu CS, Helman E, Taylor-Weiner A, McKenna A, DeLuca DS, Lawrence MS, Ambrogio L, Sougnez C, Sivachenko A, Walensky LD, Wagle N, Mora J, de Torres C, Lavarino C, Dos Santos Aguiar S, Yunes JA, Brandalise SR, Mercado-Celis GE, Melendez-Zajgla J, Cárdenas-Cardós R, Velasco-Hidalgo L, Roberts CW, Garraway LA, Rodriguez-Galindo C, Gabriel SB, Lander ES, Golub TR, Orkin SH, Getz G, Janeway KA. Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma. Proc Natl Acad Sci U S A 2014; 111:E5564-73. PubMed
  • 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. EWS-FLI1 utilizes divergent chromatin remodeling mechanisms to directly activate or repress enhancer elements in Ewing sarcoma. Cancer Cell 2014; 26:668-81. PubMed
  • Suvà ML, Rheinbay E, Gillespie SM, Patel AP, Wakimoto H, Rabkin SD, Riggi N, Chi AS, Cahill DP, Nahed BV, Curry WT, Martuza RL, Rivera MN, Rossetti N, Kasif S, Beik S, Kadri S, Tirosh I, Wortman I, Shalek AK, Rozenblatt-Rosen O, Regev A, Louis DN, Bernstein BE. Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells. Cell 2014; 157:580-94. PubMed
  • Rheinbay E, Suvà ML, Gillespie SM, Wakimoto H, Patel AP, Shahid M, Oksuz O, Rabkin SD, Martuza RL, Rivera MN, Louis DN, Kasif S, Chi AS, Bernstein BE. An aberrant transcription factor network essential for Wnt signaling and stem cell maintenance in glioblastoma. Cell Rep 2013; 3:1567-79. PubMed
  • Janiszewska M, Suvà ML, Riggi N, Houtkooper RH, Auwerx J, Clément-Schatlo V, Radovanovic I, Rheinbay E, Provero P, Stamenkovic I. Imp2 controls oxidative phosphorylation and is crucial for preserving glioblastoma cancer stem cells. Genes Dev 2012; 26:1926-44. PubMed
  • Rheinbay E, Louis DN, Bernstein BE, Suvà ML. A tell-tail sign of chromatin: histone mutations drive pediatric glioblastoma. Cancer Cell 2012; 21:329-31. PubMed
  • Ku M, Jaffe JD, Koche RP, Rheinbay E, Endoh M, Koseki H, Carr SA, Bernstein BE. H2A.Z landscapes and dual modifications in pluripotent and multipotent stem cells underlie complex genome regulatory functions. Genome Biol 2014; 13:R85. PubMed
  • Aiden AP, Rivera MN, Rheinbay E, Ku M, Coffman EJ, Truong TT, Vargas SO, Lander ES, Haber DA, Bernstein BE. Wilms tumor chromatin profiles highlight stem cell properties and a renal developmental network. Cell Stem Cell 2010; 6:591-602. PubMed
  • Butler G, Rasmussen MD, Lin MF, Santos MA, Sakthikumar S, Munro CA, Rheinbay E, Grabherr M, Forche A, Reedy JL, Agrafioti I, Arnaud MB, Bates S, Brown AJ, Brunke S, Costanzo MC, Fitzpatrick DA, de Groot PW, Harris D, Hoyer LL, Hube B, Klis FM, Kodira C, Lennard N, Logue ME, Martin R, Neiman AM, Nikolaou E, Quail MA, Quinn J, Santos MC, Schmitzberger FF, Sherlock G, Shah P, Silverstein KA, Skrzypek MS, Soll D, Staggs R, Stansfield I, Stumpf MP, Sudbery PE, Srikantha T, Zeng Q, Berman J, Berriman M, Heitman J, Gow NA, Lorenz MC, Birren BW, Kellis M, Cuomo CA. Evolution of pathogenicity and sexual reproduction in eight Candida genomes. Nature 2019; 459:657-62. PubMed
  • Ku M,Koche RP,Rheinbay E,Mendenhall EM,Endoh M,Mikkelsen TS,Presser A,Nusbaum C,Xie X,Chi AS,Adli M,Kasif S,Ptaszek LM,Cowan CA,Lander ES,Koseki H,Bernstein BE. Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. PLoS Genet 2008; 4:e1000242. PubMed
  • Meraldi P, McAinsh AD, Rheinbay E, Sorger PK. Phylogenetic and structural analysis of centromeric DNA and kinetochore proteins. Genome Biol 2018; 7:R23. PubMed
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