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W. Nicholas Haining, BM, BCh


Pediatric Hematology/Oncology

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Physician

  • Adjunct, Department of Immunology and Virology
  • Assistant Professor, Pediatric Oncology
  • Associate Professor of Pediatrics, Harvard Medical School
  • Associate Member, Broad Institute of MIT and Harvard

Clinical Interests

  • Biological therapy/immunotherapy
  • Hematopoietic stem cell transplantation

Contact Information

  • Appointments617-632-3961
  • Office Phone Number617-632-5293
  • Fax617-632-4410

Board Certification:

  • Pediatric Hematology/Oncology, 2000
  • Pediatrics, 1998

Fellowship:

  • Boston Children's Hospital/Dana-Farber Cancer Institute, Pediatric Hematology/Oncology

Residency:

  • Boston Combined Residency Program, Boston Children's Hospital/Boston Medical Center, Pediatrics

Medical School:

  • Oxford University

Research

About the Haining Lab



The Haining Laboratory studies the molecular mechanisms that impair T cell function in cancer and chronic infections using cellular immunology, chemical biology, and functional genomics to understand the regulatory circuits that drive loss of function by exhausted T cells. We are interested in developing novel therapeutic approaches to rescue function in exhausted T cells.



In our studies of functional and dysfunctional exhausted CD8 T cells, we used transcriptional profiling of rare populations of virus-specific CD8 T cells from human blood to identify the molecular differences between effective and ineffective T-cell responses in HIV. These studies revealed a mechanism by which PD-1 coordinately upregulates a program of genes, including the transcription factor BATF, which impairs T-cell function. Using chemical screens to identify small molecules that reverse inhibition caused by the receptor PD-1, we are developing novel genetic and computational approaches to match active compounds to their target molecules.



We have also developed a novel strategy for in vivo testing of regulators of T cell function in which an inducible shRNA construct is transduced into hematopoietic stem cells using a lentiviral vector, enabling in vivo gene knockdown without subsequent manipulation. This approach is particularly valuable for studying key genes that control endogenous tumor immunity.

Yates K, Bi K, Haining WN, Cantor H, Kim HJ. Comparative transcriptome analysis reveals distinct genetic modules associated with Helios expression in intratumoral regulatory T cells. Proc Natl Acad Sci U S A. 2018 Feb 27; 115(9):2162-2167.
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Akondy RS, Fitch M, Edupuganti S, Yang S, Kissick HT, Li KW, Youngblood BA, Abdelsamed HA, McGuire DJ, Cohen KW, Alexe G, Nagar S, McCausland MM, Gupta S, Tata P, Haining WN, McElrath MJ, Zhang D, Hu B, Greenleaf WJ, Goronzy JJ, Mulligan MJ, Hellerstein M, Ahmed R. Origin and differentiation of human memory CD8 T cells after vaccination. Nature. 2017 Dec 21; 552(7685):362-367.
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Deng J, Wang ES, Jenkins RW, Li S, Dries R, Yates K, Chhabra S, Huang W, Liu H, Aref AR, Ivanova E, Paweletz CP, Bowden M, Zhou CW, Herter-Sprie GS, Sorrentino JA, Bisi JE, Lizotte PH, Merlino AA, Quinn MM, Bufe LE, Yang A, Zhang Y, Zhang H, Gao P, Chen T, Cavanaugh ME, Rode AJ, Haines E, Roberts PJ, Strum JC, Richards WG, Lorch JH, Parangi S, Gunda V, Boland GM, Bueno R, Palakurthi S, Freeman GJ, Ritz J, Haining WN, Sharpless NE, Arthanari H, Shapiro GI, Barbie DA, Gray NS, Wong KK. CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation. Cancer Discov. 2018 Feb; 8(2):216-233.
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Wolski D, Foote PK, Chen DY, Lewis-Ximenez LL, Fauvelle C, Aneja J, Walker A, Tonnerre P, Torres-Cornejo A, Kvistad D, Imam S, Waring MT, Tully DC, Allen TM, Chung RT, Timm J, Haining WN, Kim AY, Baumert TF, Lauer GM. Early Transcriptional Divergence Marks Virus-Specific Primary Human CD8+ T Cells in Chronic versus Acute Infection. Immunity. 2017 10 17; 47(4):648-663.e8.
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Afik S, Yates KB, Bi K, Darko S, Godec J, Gerdemann U, Swadling L, Douek DC, Klenerman P, Barnes EJ, Sharpe AH, Haining WN, Yosef N. Targeted reconstruction of T cell receptor sequence from single cell RNA-seq links CDR3 length to T cell differentiation state. Nucleic Acids Res. 2017 Sep 19; 45(16):e148.
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Manguso RT, Pope HW, Zimmer MD, Brown FD, Yates KB, Miller BC, Collins NB, Bi K, LaFleur MW, Juneja VR, Weiss SA, Lo J, Fisher DE, Miao D, Van Allen E, Root DE, Sharpe AH, Doench JG, Haining WN. In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target. Nature. 2017 07 27; 547(7664):413-418.
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Wang H, Nicolay BN, Chick JM, Gao X, Geng Y, Ren H, Gao H, Yang G, Williams JA, Suski JM, Keibler MA, Sicinska E, Gerdemann U, Haining WN, Roberts TM, Polyak K, Gygi SP, Dyson NJ, Sicinski P. The metabolic function of cyclin D3-CDK6 kinase in cancer cell survival. Nature. 2017 06 15; 546(7658):426-430.
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Juneja VR, McGuire KA, Manguso RT, LaFleur MW, Collins N, Haining WN, Freeman GJ, Sharpe AH. PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity. J Exp Med. 2017 Apr 03; 214(4):895-904.
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Beyaz S, Kim JH, Pinello L, Xifaras ME, Hu Y, Huang J, Kerenyi MA, Das PP, Barnitz RA, Herault A, Dogum R, Haining WN, Yilmaz ÖH, Passegue E, Yuan GC, Orkin SH, Winau F. The histone demethylase UTX regulates the lineage-specific epigenetic program of invariant natural killer T cells. Nat Immunol. 2017 02; 18(2):184-195.
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Sen DR, Kaminski J, Barnitz RA, Kurachi M, Gerdemann U, Yates KB, Tsao HW, Godec J, LaFleur MW, Brown FD, Tonnerre P, Chung RT, Tully DC, Allen TM, Frahm N, Lauer GM, Wherry EJ, Yosef N, Haining WN. The epigenetic landscape of T cell exhaustion. Science. 2016 12 02; 354(6316):1165-1169.
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Pauken KE, Sammons MA, Odorizzi PM, Manne S, Godec J, Khan O, Drake AM, Chen Z, Sen DR, Kurachi M, Barnitz RA, Bartman C, Bengsch B, Huang AC, Schenkel JM, Vahedi G, Haining WN, Berger SL, Wherry EJ. Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade. Science. 2016 12 02; 354(6316):1160-1165.
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Sage PT, Ron-Harel N, Juneja VR, Sen DR, Maleri S, Sungnak W, Kuchroo VK, Haining WN, Chevrier N, Haigis M, Sharpe AH. Suppression by TFR cells leads to durable and selective inhibition of B cell effector function. Nat Immunol. 2016 Dec; 17(12):1436-1446.
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Provine NM, Larocca RA, Aid M, Penaloza-MacMaster P, Badamchi-Zadeh A, Borducchi EN, Yates KB, Abbink P, Kirilova M, Ng'ang'a D, Bramson J, Haining WN, Barouch DH. Immediate Dysfunction of Vaccine-Elicited CD8+ T Cells Primed in the Absence of CD4+ T Cells. J Immunol. 2016 09 01; 197(5):1809-22.
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Beura LK, Hamilton SE, Bi K, Schenkel JM, Odumade OA, Casey KA, Thompson EA, Fraser KA, Rosato PC, Filali-Mouhim A, Sekaly RP, Jenkins MK, Vezys V, Haining WN, Jameson SC, Masopust D. Normalizing the environment recapitulates adult human immune traits in laboratory mice. Nature. 2016 Apr 28; 532(7600):512-6.
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Reese TA, Bi K, Kambal A, Filali-Mouhim A, Beura LK, Bürger MC, Pulendran B, Sekaly RP, Jameson SC, Masopust D, Haining WN, Virgin HW. Sequential Infection with Common Pathogens Promotes Human-like Immune Gene Expression and Altered Vaccine Response. Cell Host Microbe. 2016 May 11; 19(5):713-9.
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Pesenacker AM, Wang AY, Singh A, Gillies J, Kim Y, Piccirillo CA, Nguyen D, Haining WN, Tebbutt SJ, Panagiotopoulos C, Levings MK. A Regulatory T-Cell Gene Signature Is a Specific and Sensitive Biomarker to Identify Children With New-Onset Type 1 Diabetes. Diabetes. 2016 04; 65(4):1031-9.
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Godec J, Tan Y, Liberzon A, Tamayo P, Bhattacharya S, Butte AJ, Mesirov JP, Haining WN. Compendium of Immune Signatures Identifies Conserved and Species-Specific Biology in Response to Inflammation. Immunity. 2016 Jan 19; 44(1):194-206.
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Gupta PK, Godec J, Wolski D, Adland E, Yates K, Pauken KE, Cosgrove C, Ledderose C, Junger WG, Robson SC, Wherry EJ, Alter G, Goulder PJ, Klenerman P, Sharpe AH, Lauer GM, Haining WN. CD39 Expression Identifies Terminally Exhausted CD8+ T Cells. PLoS Pathog. 2015 Oct; 11(10):e1005177.
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Kim HJ, Barnitz RA, Kreslavsky T, Brown FD, Moffett H, Lemieux ME, Kaygusuz Y, Meissner T, Holderried TA, Chan S, Kastner P, Haining WN, Cantor H. Stable inhibitory activity of regulatory T cells requires the transcription factor Helios. Science. 2015 Oct 16; 350(6258):334-9.
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Plumlee CR, Obar JJ, Colpitts SL, Jellison ER, Haining WN, Lefrancois L, Khanna KM. Early Effector CD8 T Cells Display Plasticity in Populating the Short-Lived Effector and Memory-Precursor Pools Following Bacterial or Viral Infection. Sci Rep. 2015 Jul 20; 5:12264.
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Tan Y, Wu F, Tamayo P, Haining WN, Mesirov JP. Constellation Map: Downstream visualization and interpretation of gene set enrichment results. F1000Res. 2015; 4:167.
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Penaloza-MacMaster P, Barber DL, Wherry EJ, Provine NM, Teigler JE, Parenteau L, Blackmore S, Borducchi EN, Larocca RA, Yates KB, Shen H, Haining WN, Sommerstein R, Pinschewer DD, Ahmed R, Barouch DH. Vaccine-elicited CD4 T cells induce immunopathology after chronic LCMV infection. Science. 2015 Jan 16; 347(6219):278-82.
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Godec J, Cowley GS, Barnitz RA, Alkan O, Root DE, Sharpe AH, Haining WN. Inducible RNAi in vivo reveals that the transcription factor BATF is required to initiate but not maintain CD8+ T-cell effector differentiation. Proc Natl Acad Sci U S A. 2015 Jan 13; 112(2):512-7.
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Stelekati E, Shin H, Doering TA, Dolfi DV, Ziegler CG, Beiting DP, Dawson L, Liboon J, Wolski D, Ali MA, Katsikis PD, Shen H, Roos DS, Haining WN, Lauer GM, Wherry EJ. Bystander chronic infection negatively impacts development of CD8(+) T cell memory. Immunity. 2014 May 15; 40(5):801-13.
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Kurachi M, Barnitz RA, Yosef N, Odorizzi PM, DiIorio MA, Lemieux ME, Yates K, Godec J, Klatt MG, Regev A, Wherry EJ, Haining WN. The transcription factor BATF operates as an essential differentiation checkpoint in early effector CD8+ T cells. Nat Immunol. 2014 Apr; 15(4):373-83.
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Haining WN. Strength in numbers: comparing vaccine signatures the modular way. Nat Immunol. 2014 Feb; 15(2):139-41.
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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 Feb 27; 123(9):1412-21.
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Tan Y, Tamayo P, Nakaya H, Pulendran B, Mesirov JP, Haining WN. Gene signatures related to B-cell proliferation predict influenza vaccine-induced antibody response. Eur J Immunol. 2014 Jan; 44(1):285-95.
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Henrickson SE, Perro M, Loughhead SM, Senman B, Stutte S, Quigley M, Alexe G, Iannacone M, Flynn MP, Omid S, Jesneck JL, Imam S, Mempel TR, Mazo IB, Haining WN, von Andrian UH. Antigen availability determines CD8? T cell-dendritic cell interaction kinetics and memory fate decisions. Immunity. 2013 Sep 19; 39(3):496-507.
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Barnitz RA, Imam S, Yates K, Haining WN. Isolation of RNA and the synthesis and amplification of cDNA from antigen-specific T cells for genome-wide expression analysis. Methods Mol Biol. 2013; 979:161-73.
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Huang AY, Haining WN, Barkauskas DS, Myers JT, Petrosiute A, Garrett AP, Singh K, Cooke KR, Kean LS. Viewing transplantation immunology through today's lens: new models, new imaging, and new insights. Biol Blood Marrow Transplant. 2013 Jan; 19(1 Suppl):S44-51.
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Haining WN. Thinking inside the box: how T cell inhibitory receptors signal. Nat Med. 2012 Sep; 18(9):1338-9.
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Butte MJ, Lee SJ, Jesneck J, Keir ME, Haining WN, Sharpe AH. CD28 costimulation regulates genome-wide effects on alternative splicing. PLoS One. 2012; 7(6):e40032.
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Haining WN, Pulendran B. Identifying gnostic predictors of the vaccine response. Curr Opin Immunol. 2012 Jun; 24(3):332-6.
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Haining WN. The numerology of T cell functional diversity. Immunity. 2012 Jan 27; 36(1):10-2.
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Haining WN. Travels in time: assessing the functional complexity of T cells. Proc Natl Acad Sci U S A. 2012 Jan 31; 109(5):1359-60.
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Haining WN, Barnitz RA. Deconvolving heterogeneity in the CD8+ T-cell response to HIV. Curr Opin HIV AIDS. 2012 Jan; 7(1):38-43.
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West EE, Youngblood B, Tan WG, Jin HT, Araki K, Alexe G, Konieczny BT, Calpe S, Freeman GJ, Terhorst C, Haining WN, Ahmed R. Tight regulation of memory CD8(+) T cells limits their effectiveness during sustained high viral load. Immunity. 2011 Aug 26; 35(2):285-98.
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Nakaya HI, Wrammert J, Lee EK, Racioppi L, Marie-Kunze S, Haining WN, Means AR, Kasturi SP, Khan N, Li GM, McCausland M, Kanchan V, Kokko KE, Li S, Elbein R, Mehta AK, Aderem A, Subbarao K, Ahmed R, Pulendran B. Systems biology of vaccination for seasonal influenza in humans. Nat Immunol. 2011 Jul 10; 12(8):786-95.
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Duraiswamy J, Ibegbu CC, Masopust D, Miller JD, Araki K, Doho GH, Tata P, Gupta S, Zilliox MJ, Nakaya HI, Pulendran B, Haining WN, Freeman GJ, Ahmed R. Phenotype, function, and gene expression profiles of programmed death-1(hi) CD8 T cells in healthy human adults. J Immunol. 2011 Apr 01; 186(7):4200-12.
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Novershtern N, Subramanian A, Lawton LN, Mak RH, Haining WN, McConkey ME, Habib N, Yosef N, Chang CY, Shay T, Frampton GM, Drake AC, Leskov I, Nilsson B, Preffer F, Dombkowski D, Evans JW, Liefeld T, Smutko JS, Chen J, Friedman N, Young RA, Golub TR, Regev A, Ebert BL. Densely interconnected transcriptional circuits control cell states in human hematopoiesis. Cell. 2011 Jan 21; 144(2):296-309.
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Quigley M, Pereyra F, Nilsson B, Porichis F, Fonseca C, Eichbaum Q, Julg B, Jesneck JL, Brosnahan K, Imam S, Russell K, Toth I, Piechocka-Trocha A, Dolfi D, Angelosanto J, Crawford A, Shin H, Kwon DS, Zupkosky J, Francisco L, Freeman GJ, Wherry EJ, Kaufmann DE, Walker BD, Ebert B, Haining WN. Transcriptional analysis of HIV-specific CD8+ T cells shows that PD-1 inhibits T cell function by upregulating BATF. Nat Med. 2010 Oct; 16(10):1147-51.
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Haining WN, Wherry EJ. Integrating genomic signatures for immunologic discovery. Immunity. 2010 Feb 26; 32(2):152-61.
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Kalia V, Sarkar S, Subramaniam S, Haining WN, Smith KA, Ahmed R. Prolonged interleukin-2Ralpha expression on virus-specific CD8+ T cells favors terminal-effector differentiation in vivo. Immunity. 2010 Jan 29; 32(1):91-103.
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Blackburn SD, Shin H, Haining WN, Zou T, Workman CJ, Polley A, Betts MR, Freeman GJ, Vignali DA, Wherry EJ. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol. 2009 Jan; 10(1):29-37.
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Haining WN, Davies J, Kanzler H, Drury L, Brenn T, Evans J, Angelosanto J, Rivoli S, Russell K, George S, Sims P, Neuberg D, Li X, Kutok J, Morgan J, Wen P, Demetri G, Coffman RL, Nadler LM. CpG oligodeoxynucleotides alter lymphocyte and dendritic cell trafficking in humans. Clin Cancer Res. 2008 Sep 01; 14(17):5626-34.
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Haining WN, Angelosanto J, Brosnahan K, Ross K, Hahn C, Russell K, Drury L, Norton S, Nadler L, Stegmaier K. High-throughput gene expression profiling of memory differentiation in primary human T cells. BMC Immunol. 2008 Aug 01; 9:44.
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Haining WN, Ebert BL, Subrmanian A, Wherry EJ, Eichbaum Q, Evans JW, Mak R, Rivoli S, Pretz J, Angelosanto J, Smutko JS, Walker BD, Kaech SM, Ahmed R, Nadler LM, Golub TR. Identification of an evolutionarily conserved transcriptional signature of CD8 memory differentiation that is shared by T and B cells. J Immunol. 2008 Aug 01; 181(3):1859-68.
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Sarkar S, Kalia V, Haining WN, Konieczny BT, Subramaniam S, Ahmed R. Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates. J Exp Med. 2008 Mar 17; 205(3):625-40.
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Wherry EJ, Ha SJ, Kaech SM, Haining WN, Sarkar S, Kalia V, Subramaniam S, Blattman JN, Barber DL, Ahmed R. Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity. 2007 Oct; 27(4):670-84.
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Maia S, Haining WN, Ansén S, Xia Z, Armstrong SA, Seth NP, Ghia P, den Boer ML, Pieters R, Sallan SE, Nadler LM, Cardoso AA. Gene expression profiling identifies BAX-delta as a novel tumor antigen in acute lymphoblastic leukemia. Cancer Res. 2005 Nov 01; 65(21):10050-8.
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Haining WN, Neuberg DS, Keczkemethy HL, Evans JW, Rivoli S, Gelman R, Rosenblatt HM, Shearer WT, Guenaga J, Douek DC, Silverman LB, Sallan SE, Guinan EC, Nadler LM. Antigen-specific T-cell memory is preserved in children treated for acute lymphoblastic leukemia. Blood. 2005 Sep 01; 106(5):1749-54.
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Haining WN, Cardoso AA, Keczkemethy HL, Fleming M, Neuberg D, DeAngelo DJ, Stone RM, Galinsky I, Silverman LB, Sallan SE, Nadler LM, Guinan EC. Failure to define window of time for autologous tumor vaccination in patients with newly diagnosed or relapsed acute lymphoblastic leukemia. Exp Hematol. 2005 Mar; 33(3):286-94.
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Haining WN, Evans JW, Seth NP, Callaway GD, Wucherpfennig KW, Nadler LM, Guinan EC. Measuring T cell immunity to influenza vaccination in children after haemopoietic stem cell transplantation. Br J Haematol. 2004 Nov; 127(3):322-5.
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Haining WN, Anderson DG, Little SR, von Bergwelt-Baildon MS, Cardoso AA, Alves P, Kosmatopoulos K, Nadler LM, Langer R, Kohane DS, von Berwelt-Baildon MS. pH-triggered microparticles for peptide vaccination. J Immunol. 2004 Aug 15; 173(4):2578-85.
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Cardoso AA, Veiga JP, Ghia P, Afonso HM, Haining WN, Sallan SE, Nadler LM. Adoptive T-cell therapy for B-cell acute lymphoblastic leukemia: preclinical studies. Blood. 1999 Nov 15; 94(10):3531-40.
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Haining WN, Carboy-Newcomb C, Wei CL, Steller H. The proapoptotic function of Drosophila Hid is conserved in mammalian cells. Proc Natl Acad Sci U S A. 1999 Apr 27; 96(9):4936-41.
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Noel GJ, Barenkamp SJ, St Geme JW, Haining WN, Mosser DM. High-molecular-weight surface-exposed proteins of Haemophilus influenzae mediate binding to macrophages. J Infect Dis. 1994 Feb; 169(2):425-9.
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Bridges AB, Faed M, Boxer M, Haining WM, Pringle TH, McNeill GP. Marfan syndrome affecting four generations of a family without ocular involvement. Postgrad Med J. 1991 Jun; 67(788):538-42.
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