W. Nicholas Haining, BCh, BM

Research Overview

Dr. Haining is a physician-scientist at the Dana-Farber Cancer Institute and the Broad Institute. His laboratory aims to understand the mechanisms that impair T cell function in cancer and chronic viral disease. To achieve this goal, he has applied genomic tools and computational biology to identify central mechanisms that regulate T cell function. As a post-doctoral fellow he developed new techniques to analyze the gene expression profile of antigen-specific T cells, allowing the signatures of these rare populations to be studied for the first time. He applied novel computational techniques to show that diverse populations of memory lymphocytes share a common differentiation program (J. Immunology 2008). His laboratory has pioneered the application of integrative genomic techniques to identify the mechanisms regulating T cell function in humans. His lab used these approaches to discover a new mechanism that explains defective T cell function in HIV, by showing that the transcription factor BATF is regulated by the receptor PD-1 and inhibits HIV-specific T cells (Nature Medicine, 2010). In recognition of these studies, he was awarded the 2010 Presidential Early Career Award for Scientists and Engineers.

About Nicholas Haining

Dr. Haining is a physician-scientist who received his undergraduate and medical degree from Oxford University, UK. He moved to the United States in 1993 to complete medical training in Pediatrics at Children's Hospital, Boston, and subsequently in Pediatric Hematology/Oncology at Dana-Farber Cancer Institute. After post-doctoral research at MIT and Dana-Farber Cancer Institute, he was appointed to the faculty as Assistant Professor of Pediatrics in 2007 in the Department of Pediatric Oncology. In 2011, he joined the faculty of the Broad Institute of Harvard and MIT as an Associate Member.

For more information, contact Dr. Haining directly:

Website: The Haining Lab

Email: nicholas_haining@dfci.harvard.edu

Twitter: @nickhaining

Key Publications

• Haining WN, Anderson DG, Little SR, von Bergwelt-Baildon MS, Cardoso AA, Alves P, Kosmatopoulos K, Nadler LM, Langer R, Kohane DS. pH-triggered microparticles for peptide vaccination. J Immunol 2004, 173:2578-2585.(PMID: 15294974)

• 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, 127:322-325.(PMID: 15491293)

• 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, 33:286-294.(PMID: 15730852)

• 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, 106:1749-1754.(PMID: 15920008)

• Maia S, Haining WN, Ansen 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, 65:10050-10058.(PMID: 16267031)

• 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, 27:670-684.(PMID: 17950003)

• 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, 9:44.(PMID: 18673556)

• 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, 14:5626-5634.(PMID: 18765557)

• 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, 181:1859-1868.(PMID: 18641323)

• 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, 205:625-640.(PMID: 18316415)

• 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, 10:29-37.(PMID: 19043418)

• 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, 32:91-103.(PMID: 20096608)

• 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, 16:1147-1151.(PMID: 20890291)

• 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. Journal of immunology 2011, 186:4200-4212.(PMID: 21383243)

• 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. Nature immunology 2011, 12:786-795.(PMID: 21743478)

• 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, 144:296-309.(PMID: 21241896)

• 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, 35:285-298.(PMID: 21856186)
  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:e40032.(PMID: 22768209)