Photo of Nir Hacohen,  PhD

Nir Hacohen, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 724-3768
Fax: (617) 726-5651

Nir Hacohen, PhD

Massachusetts General Hospital


  • Associate Professor, Medicine, Harvard Medical School
  • Immunologist, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital


Research Abstract

Dr. Hacohen is an immunologist, geneticist and systems biologist focused on dissecting the basic mechanisms of immunity, developing and applying genetic technologies that accelerate the study of the immune system, and deciphering and treating human diseases -- including cancer and immune disorders -- based on genomic approaches. Dr. Hacohen is a founding member of the Broad Institute’s RNAi Consortium -- a public-private partnership that has built genome-wide RNA interference libraries to silence every gene in mice and humans -- and a founding director of the Broad Immune Circuits Initiative. These efforts have put RNAi technologies in the hands of the community to address numerous biological and immunological questions.

Projects in the laboratory focus on innate immunity and dendritic cells, as well as technology development, and include: (I) developing methods for network reconstruction of pathogen-sensing pathways in mice and humans, with a focus on viral and bacterial sensing pathways; (II) dissecting how DNA is sensed by the immune system, including the role of nucleases in clearance of self DNA; (III) analyzing mechanisms underlying autoimmunity in lupus patients; (IV) uncovering interactions between tumors and the immune system; (V) testing a new generation of personalized tumor vaccines (together with Dr. Catherine Wu, DFCI).



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  • Parnas O, Jovanovic M, Eisenhaure TM, Herbst RH, Dixit A, Ye CJ, Przybylski D, Platt RJ, Tirosh I, Sanjana NE, Shalem O, Satija R, Raychowdhury R, Mertins P, Carr SA, Zhang F, Hacohen N, Regev A. A Genome-wide CRISPR Screen in Primary Immune Cells to Dissect Regulatory Networks. Cell 2015. PubMed
  • Ramirez-Ortiz ZG, Prasad A, Griffith JW, Pendergraft WF, Cowley GS, Root DE, Tai M, Luster AD, El Khoury J, Hacohen N, Means TK. The receptor TREML4 amplifies TLR7-mediated signaling during antiviral responses and autoimmunity. Nat Immunol 2015. PubMed
  • Jovanovic M, Rooney MS, Mertins P, Przybylski D, Chevrier N, Satija R, Rodriguez EH, Fields AP, Schwartz S, Raychowdhury R, Mumbach MR, Eisenhaure T, Rabani M, Gennert D, Lu D, Delorey T, Weissman JS, Carr SA, Hacohen N, Regev A. Immunogenetics. Dynamic profiling of the protein life cycle in response to pathogens. Science 2015; 347:1259038. PubMed
  • Park SM, Gönen M, Vu L, Minuesa G, Tivnan P, Barlowe TS, Taggart J, Lu Y, Deering RP, Hacohen N, Figueroa ME, Paietta E, Fernandez HF, Tallman MS, Melnick A, Levine R, Leslie C, Lengner CJ, Kharas MG. Musashi2 sustains the mixed-lineage leukemia-driven stem cell regulatory program. J Clin Invest 2015; 125:1286-98. PubMed
  • Rooney MS, Shukla SA, Wu CJ, Getz G, Hacohen N. Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell 2015; 160:48-61. PubMed
  • Rabani M, Raychowdhury R, Jovanovic M, Rooney M, Stumpo DJ, Pauli A, Hacohen N, Schier AF, Blackshear PJ, Friedman N, Amit I, Regev A. High-resolution sequencing and modeling identifies distinct dynamic RNA regulatory strategies. Cell 2014; 159:1698-710. PubMed
  • Landau DA, Clement K, Ziller MJ, Boyle P, Fan J, Gu H, Stevenson K, Sougnez C, Wang L, Li S, Kotliar D, Zhang W, Ghandi M, Garraway L, Fernandes SM, Livak KJ, Gabriel S, Gnirke A, Lander ES, Brown JR, Neuberg D, Kharchenko PV, Hacohen N, Getz G, Meissner A, Wu CJ. Locally disordered methylation forms the basis of intratumor methylome variation in chronic lymphocytic leukemia. Cancer Cell 2014; 26:813-25. PubMed
  • Lan YY, Londoño D, Bouley R, Rooney MS, Hacohen N. Dnase2a Deficiency Uncovers Lysosomal Clearance of Damaged Nuclear DNA via Autophagy. Cell Rep 2014; 9:180-92. PubMed
  • Platt RJ, Chen S, Zhou Y, Yim MJ, Swiech L, Kempton HR, Dahlman JE, Parnas O, Eisenhaure TM, Jovanovic M, Graham DB, Jhunjhunwala S, Heidenreich M, Xavier RJ, Langer R, Anderson DG, Hacohen N, Regev A, Feng G, Sharp PA, Zhang F. CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling. Cell 2014; 159:440-55. PubMed
  • Wang L, Shalek AK, Lawrence M, Ding R, Gaublomme JT, Pochet N, Stojanov P, Sougnez C, Shukla SA, Stevenson KE, Zhang W, Wong J, Sievers QL, MacDonald BT, Vartanov AR, Goldstein NR, Neuberg D, He X, Lander E, Hacohen N, Regev A, Getz G, Brown JR, Park H, Wu CJ. Somatic mutation as a mechanism of Wnt/β-catenin pathway activation in CLL. Blood 2014. PubMed
  • Rajasagi M, Shukla SA, Fritsch EF, Keskin DB, DeLuca D, Carmona E, Zhang W, Sougnez C, Cibulskis K, Sidney J, Stevenson K, Ritz J, Neuberg D, Brusic V, Gabriel S, Lander ES, Getz G, Hacohen N, Wu CJ. Systematic identification of personal tumor-specific neoantigens in chronic lymphocytic leukemia. Blood 2014. PubMed
  • Schwartz S, Mumbach MR, Jovanovic M, Wang T, Maciag K, Bushkin GG, Mertins P, Ter-Ovanesyan D, Habib N, Cacchiarelli D, Sanjana NE, Freinkman E, Pacold ME, Satija R, Mikkelsen TS, Hacohen N, Zhang F, Carr SA, Lander ES, Regev A. Perturbation of m6A Writers Reveals Two Distinct Classes of mRNA Methylation at Internal and 5' Sites. Cell Rep 2014. PubMed
  • Shalek AK, Satija R, Shuga J, Trombetta JJ, Gennert D, Lu D, Chen P, Gertner RS, Gaublomme JT, Yosef N, Schwartz S, Fowler B, Weaver S, Wang J, Wang X, Ding R, Raychowdhury R, Friedman N, Hacohen N, Park H, May AP, Regev A. Single-cell RNA-seq reveals dynamic paracrine control of cellular variation. Nature 2014. PubMed
  • Fritsch EF, Rajasagi M, Ott PA, Brusic V, Hacohen N, Wu CJ. HLA-Binding Properties of Tumor Neoepitopes in Humans. Cancer Immunol Res 2014; 2:522-9. PubMed
  • Zhu Z, Aref AR, Cohoon TJ, Barbie TU, Imamura Y, Yang S, Moody SE, Shen RR, Schinzel AC, Thai TC, Reibel JB, Tamayo P, Godfrey JT, Qian ZR, Page AN, Maciag K, Chan EM, Silkworth W, Labowsky MT, Rozhansky L, Mesirov JP, Gillanders WE, Ogino S, Hacohen N, Gaudet S, Eck MJ, Engelman JA, Corcoran RB, Wong KK, Hahn WC, Barbie DA. Inhibition of KRAS-driven tumorigenicity by interruption of an autocrine cytokine circuit. 2014; 4:452-65. PubMed
  • Lee MN, Ye C, Villani AC, Raj T, Li W, Eisenhaure TM, Imboywa SH, Chipendo PI, Ran FA, Slowikowski K, Ward LD, Raddassi K, McCabe C, Lee MH, Frohlich IY, Hafler DA, Kellis M, Raychaudhuri S, Zhang F, Stranger BE, Benoist CO, De Jager PL, Regev A, Hacohen N. Common genetic variants modulate pathogen-sensing responses in human dendritic cells. Science 2014; 343:1246980. PubMed
  • Bachireddy P, Hainz U, Rooney M, Pozdnyakova O, Aldridge J, Zhang W, Liao X, Hodi FS, O'Connell K, Haining WN, Goldstein NR, Canning CM, Soiffer RJ, Ritz J, Hacohen N, Alyea EP, Kim HT, Wu CJ. Reversal of in situ T-cell exhaustion during effective human antileukemia responses to donor lymphocyte infusion. Blood 2014; 123:1412-21. PubMed
  • Zhou P, Shaffer DR, Alvarez Arias DA, Nakazaki Y, Pos W, Torres AJ, Cremasco V, Dougan SK, Cowley GS, Elpek K, Brogdon J, Lamb J, Turley SJ, Ploegh HL, Root DE, Love JC, Dranoff G, Hacohen N, Cantor H, Wucherpfennig KW. In vivo discovery of immunotherapy targets in the tumour microenvironment. Nature 2014; 506:52-7. PubMed
  • Filone CM, Caballero IS, Dower K, Mendillo ML, Cowley GS, Santagata S, Rozelle DK, Yen J, Rubins KH, Hacohen N, Root DE, Hensley LE, Connor J. The master regulator of the cellular stress response (HSF1) is critical for orthopoxvirus infection. PLoS Pathog. 2014; 10:e1003904. PubMed
  • Giraud M, Jmari N, Du L, Carallis F, Nieland TJ, Perez-Campo FM, Bensaude O, Root DE, Hacohen N, Mathis D, Benoist C. An RNAi screen for Aire cofactors reveals a role for Hnrnpl in polymerase release and Aire-activated ectopic transcription. Proc Natl Acad Sci U S A 2014; 111:1491-6. PubMed
  • Park SM, Deering RP, Lu Y, Tivnan P, Lianoglou S, Al-Shahrour F, Ebert BL, Hacohen N, Leslie C, Daley GQ, Lengner CJ, Kharas MG. Musashi-2 controls cell fate, lineage bias, and TGF-硫 signaling in HSCs. J Exp Med 2014; 211:71-87. PubMed
  • Fritsch EF, Hacohen N, Wu CJ. Personal neoantigen cancer vaccines: The momentum builds. Oncoimmunology 2014; 3:e29311. PubMed
  • Ramirez-Ortiz ZG, Pendergraft WF, Prasad A, Byrne MH, Iram T, Blanchette CJ, Luster AD, Hacohen N, El Khoury J, Means TK. The scavenger receptor SCARF1 mediates the clearance of apoptotic cells and prevents autoimmunity. Nat Immunol 2013; 14:917-26. PubMed
  • Hacohen N, Fritsch EF, Carter TA, Lander ES, Wu CJ. Getting personal with neoantigen-based therapeutic cancer vaccines. Cancer Immunol Res 2014; 1:11-5. PubMed
  • Shalek AK, Satija R, Adiconis X, Gertner RS, Gaublomme JT, Raychowdhury R, Schwartz S, Yosef N, Malboeuf C, Lu D, Trombetta JJ, Gennert D, Gnirke A, Goren A, Hacohen N, Levin JZ, Park H, Regev A. Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells. Nature 2013; 498:236-40. PubMed
  • Gat-Viks I, Chevrier N, Wilentzik R, Eisenhaure T, Raychowdhury R, Steuerman Y, Shalek AK, Hacohen N, Amit I, Regev A. Deciphering molecular circuits from genetic variation underlying transcriptional responsiveness to stimuli. Nat Biotechnol 2013; 31:342-9. PubMed
  • Landau DA, Carter SL, Stojanov P, McKenna A, Stevenson K, Lawrence MS, Sougnez C, Stewart C, Sivachenko A, Wang L, Wan Y, Zhang W, Shukla SA, Vartanov A, Fernandes SM, Saksena G, Cibulskis K, Tesar B, Gabriel S, Hacohen N, Meyerson M, Lander ES, Neuberg D, Brown JR, Getz G, Wu CJ. Evolution and impact of subclonal mutations in chronic lymphocytic leukemia. Cell 2013; 152:714-26. PubMed
  • Lee MN, Roy M, Ong SE, Mertins P, Villani AC, Li W, Dotiwala F, Sen J, Doench JG, Orzalli MH, Kramnik I, Knipe DM, Lieberman J, Carr SA, Hacohen N. Identification of regulators of the innate immune response to cytosolic DNA and retroviral infection by an integrative approach. Nat Immunol 2013; 14:179-85. PubMed
  • Shalek AK, Gaublomme JT, Wang L, Yosef N, Chevrier N, Andersen MS, Robinson JT, Pochet N, Neuberg D, Gertner RS, Amit I, Brown JR, Hacohen N, Regev A, Wu CJ, Park H. Nanowire-mediated delivery enables functional interrogation of primary immune cells: application to the analysis of chronic lymphocytic leukemia. Nano Lett 2012; 12:6498-504. PubMed
  • Garber M, Yosef N, Goren A, Raychowdhury R, Thielke A, Guttman M, Robinson J, Minie B, Chevrier N, Itzhaki Z, Blecher-Gonen R, Bornstein C, Amann-Zalcenstein D, Weiner A, Friedrich D, Meldrim J, Ram O, Cheng C, Gnirke A, Fisher S, Friedman N, Wong B, Bernstein BE, Nusbaum C, Hacohen N, Regev A, Amit I. A high-throughput chromatin immunoprecipitation approach reveals principles of dynamic gene regulation in mammals. Mol Cell 2012; 47:810-22. PubMed
  • Moita CF, Chora Â, Hacohen N, Moita LF. RNAi screen for kinases and phosphatases that play a role in antigen presentation by dendritic cells. Eur J Immunol 2012; 42:1843-9. PubMed
  • Pe'er D, Hacohen N. Principles and strategies for developing network models in cancer. Cell 2011; 144:864-73. PubMed
  • Lin Y, Zhang L, Cai AX, Lee M, Zhang W, Neuberg D, Canning CM, Soiffer RJ, Alyea EP, Ritz J, Hacohen N, Means TK, Wu CJ. Effective posttransplant antitumor immunity is associated with TLR-stimulating nucleic acid-immunoglobulin complexes in humans. J Clin Invest 2011. PubMed
  • Dougan M, Dougan S, Slisz J, Firestone B, Vanneman M, Draganov D, Goyal G, Li W, Neuberg D, Blumberg R, Hacohen N, Porter D, Zawel L, Dranoff G. IAP inhibitors enhance co-stimulation to promote tumor immunity. J Exp Med 2010; 207:2195-206. PubMed
  • Colvin RA, Means TK, Diefenbach TJ, Moita LF, Friday RP, Sever S, Campanella GS, Abrazinski T, Manice LA, Moita C, Andrews NW, Wu D, Hacohen N, Luster AD. Synaptotagmin-mediated vesicle fusion regulates cell migration. Nat Immunol 2010; 11:495-502. PubMed
  • Dixit E, Boulant S, Zhang Y, Lee AS, Odendall C, Shum B, Hacohen N, Chen ZJ, Whelan SP, Fransen M, Nibert ML, Superti-Furga G, Kagan JC. Peroxisomes are signaling platforms for antiviral innate immunity. Cell 2010; 141:668-81. PubMed
  • Astier AL, Beriou G, Eisenhaure TM, Anderton SM, Hafler DA, Hacohen N. RNA interference screen in primary human T cells reveals FLT3 as a modulator of IL-10 levels. J Immunol 2010; 184:685-93. PubMed
  • Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G, Savina A, Moita CF, Schauer K, Hume AN, Freitas RP, Goud B, Benaroch P, Hacohen N, Fukuda M, Desnos C, Seabra MC, Darchen F, Amigorena S, Moita LF, Thery C. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol 2009; 12:19-30; sup pp 1-13. PubMed
  • Shapira SD, Gat-Viks I, Shum BO, Dricot A, de Grace MM, Wu L, Gupta PB, Hao T, Silver SJ, Root DE, Hill DE, Regev A, Hacohen N. A physical and regulatory map of host-influenza interactions reveals pathways in H1N1 infection. Cell 2010; 139:1255-67. PubMed
  • Ali N,Karlsson C,Aspling M,Hu G,Hacohen N,Scadden DT,Larsson J. Forward RNAi screens in primary human hematopoietic stem/progenitor cells. Blood 2009; 113:3690-5. PubMed
  • Savina A,Peres A,Cebrian I,Carmo N,Moita C,Hacohen N,Moita LF,Amigorena S. The small GTPase Rac2 controls phagosomal alkalinization and antigen crosspresentation selectively in CD8(+) dendritic cells. Immunity 2009; 30:544-55. PubMed
  • Means TK,Mylonakis E,Tampakakis E,Colvin RA,Seung E,Puckett L,Tai MF,Stewart CR,Pukkila-Worley R,Hickman SE,Moore KJ,Calderwood SB,Hacohen N,Luster AD,El Khoury J. Evolutionarily conserved recognition and innate immunity to fungal pathogens by the scavenger receptors SCARF1 and CD36. J Exp Med 2009; 206:637-53. PubMed
  • Guttman M,Amit I,Garber M,French C,Lin MF,Feldser D,Huarte M,Zuk O,Carey BW,Cassady JP,Cabili MN,Jaenisch R,Mikkelsen TS,Jacks T,Hacohen N,Bernstein BE,Kellis M,Regev A,Rinn JL,Lander ES. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 2009; 458:223-7. PubMed
  • Luo B,Cheung HW,Subramanian A,Sharifnia T,Okamoto M,Yang X,Hinkle G,Boehm JS,Beroukhim R,Weir BA,Mermel C,Barbie DA,Awad T,Zhou X,Nguyen T,Piqani B,Li C,Golub TR,Meyerson M,Hacohen N,Hahn WC,Lander ES,Sabatini DM,Root DE. Highly parallel identification of essential genes in cancer cells. Proc Natl Acad Sci U S A 2008; 105:20380-5. PubMed
  • Oberdoerffer S,Moita LF,Neems D,Freitas RP,Hacohen N,Rao A. Regulation of CD45 alternative splicing by heterogeneous ribonucleoprotein, hnRNPLL. Science 2008; 321:686-91. PubMed
  • Adams EW, Ratner DM, Seeberger PH, Hacohen N. Carbohydrate-mediated targeting of antigen to dendritic cells leads to enhanced presentation of antigen to T cells. Chembiochem 2008; 9:294-303. PubMed
  • Moffat J, Grueneberg DA, Yang X, Kim SY, Kloepfer AM, Hinkle G, Piqani B, Eisenhaure TM, Luo B, Grenier JK, Carpenter AE, Foo SY, Stewart SA, Stockwell BR, Hacohen N, Hahn WC, Lander ES, Sabatini DM, Root DE. A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen. Cell 2006; 124:1283-98. PubMed
  • Bachireddy P, Hainz U, Rooney M, Pozdnyakova O, Aldridge J, Zhang W, Liao X, Hodi FS, O'Connell K, Haining WN, Goldstein NR, Canning CM, Soiffer RJ, Ritz J, Hacohen N, Alyea EP, Kim HT, Wu CJ. Reversal of in situ T cell exhaustion during effective human anti-leukemia responses to donor lymphocyte infusion Blood 2014.