Nicholas Arpaia, PhD

  • Associate Professor of Microbiology and Immunology

On the web

Profile Headshot

Profile Navigation

Overview

Dr. Arpaia received a BS in Biochemistry from the State University of New York, Geneseo in 2006 and a PhD in Molecular and Cell Biology (Immunology and Pathogenesis) from the University of California, Berkeley in 2011. Dr. Arpaia serves as the Director of the Microbiology & Immunology Graduate Program and Associate Director of the Integrated Doctoral Program in Cellular, Molecular, and Biomedical Sciences. He was named a Searle Scholar in 2017 and received the Harold and Golden Lamport Award for Excellence in Basic Science Research in 2021.

His graduate work with Dr. Gregory M. Barton examined interactions between Salmonella typhimurium and the innate immune system and demonstrated that Toll-like receptor–sensing of S. typhimurium promotes pathogen virulence and immune evasion. As a Postdoctoral Research Fellow in the laboratory of Dr. Alexander Y. Rudensky at Memorial Sloan Kettering Cancer Center, Dr. Arpaia investigated how tissue-resident leukocytes sense changes in their local environment and identified environmental signals that drive the differentiation and specialization of regulatory T (Treg) cell subsets. He began his independent laboratory as an Assistant Professor of Microbiology & Immunology at Columbia University Irving Medical Center in 2016 and was promoted to Associate Professor (with tenure) in 2024.

Academic Appointments

  • Associate Professor of Microbiology and Immunology

Administrative Titles

  • Director of Graduate Studies, Microbiology & Immunology Graduate Program
  • Co-Associate Director of Graduate Studies, CMBS Graduate Program

Languages

  • Italian

Credentials & Experience

Education & Training

  • BS, 2006 Biochemistry, Summa Cum Laude, State University of New York at Geneseo
  • PhD, 2011 Molecular and Cell Biology (Immunology and Pathogenesis), University of California, Berkeley
  • Fellowship: 2016 Damon Runyon Cancer Research Foundation Robert Black Fellow, Memorial Sloan Kettering Cancer Center

Honors & Awards

  • 2021: Harold and Golden Lamport Award for Excellence in Basic Science Research
  • 2017: Searle Scholar
  • 2016: Tri-Institutional Breakout Prize, Memorial Sloan Kettering/Rockefeller University/Weill Cornell
  • 2013: Damon Runyon Cancer Research Foundation Robert Black Postdoctoral Fellow

Research

Dr. Arpaia's research focuses on understanding the molecular mechanisms that drive pro- vs. anti-inflammatory immune responses in mucosal barrier tissues and the tumor microenvironment.

Immunity and tolerance are achieved by balancing pro- and anti-inflammatory responses to limit or prevent collateral tissue damage while neutralizing an invading pathogen. At mucosal barriers — which are colonized by diverse communities of commensal microbes and serve to interface the internal physiology of an organism with the ever-changing external environment — fine-tuning opposing immune responses is of even greater relevance. Constant exposure to novel environmental molecules and high concentrations of microbial products that can activate innate immunity increase the risk for persistent inflammatory activation. As a result, complex immune networks operate to contextualize diverse microbial and environmental stimuli. These inputs subsequently shape mucosal immune responses and synergize to preserve mucosal barrier integrity and function. Aberrant immune responses, due to a breakdown in tolerance or defects in barrier maintenance, largely underlie the etiology of chronic mucosal inflammatory disorders.

The Arpaia Lab is committed to understanding how mucosal immune responses are coordinated to maintain homeostasis and respond to microbial infection, barrier disruption, or alterations in commensal microbial diversity — with an emphasis on how these molecular decisions are balanced within the context of host fitness and organ physiology. Our studies are geared toward uncovering pathways with the potential for therapeutic manipulation, focusing on the signals that drive pro- and anti-inflammatory immune responses within each setting. To pursue these goals, we are exploring the molecular mechanisms underlying epithelial barrier repair and investigating the contribution of commensal microbial colonization in these processes.

Research Interests

  • Host-Microbe Interactions
  • Immunometabolism
  • Mucosal Immunity
  • Tissue Repair

Selected Publications

  1. Redenti A#, Im J#, Redenti B, Li F, Rouanne M, Sheng Z, Sun W, Gurbatri CR, Huang S, Komaranchath M, Jang Y, Hahn J, Ballister ER, Vincent RL, Vardoshivilli A, Danino T*#, Arpaia N*#. Probiotic neoantigen delivery vectors for precision cancer immunotherapy. Nature. 2024. Epub ahead of print. PubMed PMID: 39415001.
  2. Li F, Yang Z, Savage TM, Vincent RL, de los Santos-Alexis K, Ahn A, Rouanne M, Mariuzza DL, Danino T, Arpaia N*. Programmable bacteria synergize with PD-1 blockade to overcome cancer cell-intrinsic immune resistance mechanisms. Sci Immunol. 2024;9(100):eadn9879. PubMed PMID: 39423284.
  3. Savage TM, Fortson KT, de los Santos-Alexis K, Oliveras Alsina A, Rouanne M, Rae SS, Gamarra JR, Shayya HJ, Kornberg A, Cavero R, Li F, Han A, Haeusler RA, Adam J, Schwabe RF, Arpaia N*. Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis. Immunity. 2024;57(2):303-318.e6. PubMed PMID: 38309273; PMCID: PMC10922825.
  4. Gurbatri CR, Radford G, Vrbanac L, Im JW, Thomas E, Coker C, Taylor SR, Jang Y, Sivan A, Rhee K, Saleh AA, Chien T, Zandkarimi F, Lia I, Lannagan TR, Wang T, Wright JA, Kobayashi H, Ng JQ, Lawrence M, Sammour T, Thomas M, Lewis M, Papanicolas L, Perry J, Fitzsimmons T, Kaazan P, Lim A, Gouskos D, Stavropoulos A, Marker J, Ostroff C, Rogers G, Arpaia N, Worthley DL, Woods SL, Danino T. Engineering tumor-colonizing E. coli Nissle 1917 for detection and treatment of colorectal neoplasia. Nat Commun. 2024;15(1):646. PubMed PMID: 38245513; PMCID: PMC10799955.
  5. Vincent RL, Gurbatri CR, Li F, Vardoshvili A, Coker C, Im J, Ballister ER, Rouanne M, Savage T, de los Santos-Alexis K, Redenti A, Brockmann L, Komaranchath M, Arpaia N, Danino T. Probiotic-guided CAR-T cells for solid tumor targeting. Science. 2023;382(6667):211-8. PubMed PMID: 37824640; PMCID: PMC10915968.
  6. Rankin LC, Kaiser KA, de los Santos-Alexis K, Park H, Uhlemann AC, Gray DHD, Arpaia N*. Dietary tryptophan deficiency promotes gut RORγt+ Treg cells at the expense of Gata3+ Treg cells and alters commensal microbiota metabolism. Cell Rep. 2023;42(3):112135. PubMed PMID: 36840944; PMCID: PMC10150404.
  7. Savage TM, Vincent RL, Rae SS, Huang LH, Ahn A, Pu K, Li F, de los Santos-Alexis K, Coker C, Danino T, Arpaia N*. Chemokines expressed by engineered bacteria recruit and orchestrate antitumor immunity. Sci Adv. 2023;9(10):eadc9436. PubMed PMID: 36888717; PMCID: PMC9995032.
  8. Kaiser KA, Loffredo LF, de los Santos-Alexis K, Ringham OR, Arpaia N*. Regulation of the alveolar regenerative niche by amphiregulin-producing regulatory T cells. J Exp Med. 2023;220(3). PubMed PMID: 36534084; PMCID: PMC9767680.
  9. Filliol A, Saito Y, Nair A, Dapito DH, Yu LX, Ravichandra A, Bhattacharjee S, Affo S, Fujiwara N, Su H, Sun Q, Savage TM, Wilson-Kanamori JR, Caviglia JM, Chin L, Chen D, Wang X, Caruso S, Kang JK, Amin AD, Wallace S, Dobie R, Yin D, Rodriguez-Fiallos OM, Yin C, Mehal A, Izar B, Friedman RA, Wells RG, Pajvani UB, Hoshida Y, Remotti HE, Arpaia N, Zucman-Rossi J, Karin M, Henderson NC, Tabas I, Schwabe RF. Opposing roles of hepatic stellate cell subpopulations in hepatocarcinogenesis. Nature. 2022;610(7931):356-65. PubMed PMID: 36198802; PMCID: PMC9949942.
  10. 10. Harimoto T, Hahn J, Chen YY, Im J, Zhang J, Hou N, Li F, Coker C, Gray K, Harr N, Chowdhury S, Pu K, Nimura C, Arpaia N, Leong KW, Danino T. A programmable encapsulation system improves delivery of therapeutic bacteria in mice. Nat Biotechnol. 2022;40(8):1259-69. PubMed PMID: 35301496; PMCID: PMC9371971.
  11. 11. Rouanne M, Adam J, Radulescu C, Letourneur D, Bredel D, Mouraud S, Goubet AG, Leduc M, Chen N, Tan TZ, Signolle N, Bigorgne A, Dussiot M, Tselikas L, Susini S, Danlos FX, Schneider AK, Chabanon R, Vacher S, Bieche I, Lebret T, Allory Y, Soria JC, Arpaia N, Kroemer G, Kepp O, Thiery JP, Zitvogel L, Marabelle A. BCG therapy downregulates HLA-I on malignant cells to subvert antitumor immune responses in bladder cancer. J Clin Invest. 2022;132(12). PubMed PMID: 35503263; PMCID: PMC9197524.
  12. 12. Kobayashi H, Gieniec KA, Lannagan TRM, Wang T, Asai N, Mizutani Y, Iida T, Ando R, Thomas EM, Sakai A, Suzuki N, Ichinose M, Wright JA, Vrbanac L, Ng JQ, Goyne J, Radford G, Lawrence MJ, Sammour T, Hayakawa Y, Klebe S, Shin AE, Asfaha S, Bettington ML, Rieder F, Arpaia N, Danino T, Butler LM, Burt AD, Leedham SJ, Rustgi AK, Mukherjee S, Takahashi M, Wang TC, Enomoto A, Woods SL, Worthley DL. The Origin and Contribution of Cancer-Associated Fibroblasts in Colorectal Carcinogenesis. Gastroenterology. 2022;162(3):890-906. PubMed PMID: 34883119; PMCID: PMC8881386.
  13. Affo S, Nair A, Brundu F, Ravichandra A, Bhattacharjee S, Matsuda M, Chin L, Filliol A, Wen W, Song X, Decker A, Worley J, Caviglia JM, Yu L, Yin D, Saito Y, Savage T, Wells RG, Mack M, Zender L, Arpaia N, Remotti HE, Rabadan R, Sims P, Leblond AL, Weber A, Riener MO, Stockwell BR, Gaublomme J, Llovet JM, Kalluri R, Michalopoulos GK, Seki E, Sia D, Chen X, Califano A, Schwabe RF. Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations. Cancer Cell. 2021;39(6):866-82 e11. PubMed PMID: 33930309; PMCID: PMC8241235.
  14. Bhattacharjee S, Hamberger F, Ravichandra A, Miller M, Nair A, Affo S, Filliol A, Chin L, Savage TM, Yin D, Wirsik NM, Mehal A, Arpaia N, Seki E, Mack M, Zhu D, Sims PA, Kalluri R, Stanger BZ, Olive KP, Schmidt T, Wells RG, Mederacke I, Schwabe RF. Tumor restriction by type I collagen opposes tumor-promoting effects of cancer-associated fibroblasts. J Clin Invest. 2021;131(11). PubMed PMID: 33905375; PMCID: PMC8159701.
  15. 15. Gurbatri CR, Lia I, Vincent R, Coker C, Castro S, Treuting PM, Hinchliffe TE, Arpaia N, Danino T. Engineered probiotics for local tumor delivery of checkpoint blockade nanobodies. Sci Transl Med. 2020;12(530). PubMed PMID: 32051224; PMCID: PMC7685004.
  16. 16. Chowdhury S, Castro S, Coker C, Hinchliffe TE, Arpaia N*#, Danino T*#. Programmable bacteria induce durable tumor regression and systemic antitumor immunity. Nat Med. 2019;25(7):1057-63. PubMed PMID: 31270504; PMCID: PMC6688650.
  17. 17. Yen B, Fortson KT, Rothman NJ, Arpaia N*#, Reiner SL*#. Clonal Bifurcation of Foxp3 Expression Visualized in Thymocytes and T Cells. Immunohorizons. 2018;2(4):119-28. PubMed PMID: 29707696; PMCID: PMC5922779.
  18. Green JA#, Arpaia N#, Schizas M, Dobrin A, Rudensky AY. A nonimmune function of T cells in promoting lung tumor progression. J Exp Med. 2017;214(12):3565-75. PubMed PMID: 29038367; PMCID: PMC5716034.
  19. Arpaia N, Green JA, Moltedo B, Arvey A, Hemmers S, Yuan S, Treuting PM, Rudensky AY. A Distinct Function of Regulatory T Cells in Tissue Protection. Cell. 2015;162(5):1078-89. PubMed PMID: 26317471; PMCID: PMC4603556.
  20. Jenq RR, Taur Y, Devlin SM, Ponce DM, Goldberg JD, Ahr KF, Littmann ER, Ling L, Gobourne AC, Miller LC, Docampo MD, Peled JU, Arpaia N, Cross JR, Peets TK, Lumish MA, Shono Y, Dudakov JA, Poeck H, Hanash AM, Barker JN, Perales MA, Giralt SA, Pamer EG, van den Brink MR. Intestinal Blautia Is Associated with Reduced Death from Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2015;21(8):1373-83. PubMed PMID: 25977230; PMCID: PMC4516127.
  21. Sivick KE, Arpaia N, Reiner GL, Lee BL, Russell BR, Barton GM. Toll-like receptor-deficient mice reveal how innate immune signaling influences Salmonella virulence strategies. Cell Host Microbe. 2014;15(2):203-13. PubMed PMID: 24528866; PMCID: PMC3979597.
  22. Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, Liu H, Cross JR, Pfeffer K, Coffer PJ, Rudensky AY. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504(7480):451-5. PubMed PMID: 24226773; PMCID: PMC3869884.
  23. Mouchess ML, Arpaia N, Souza G, Barbalat R, Ewald SE, Lau L, Barton GM. Transmembrane mutations in Toll-like receptor 9 bypass the requirement for ectodomain proteolysis and induce fatal inflammation. Immunity. 2011;35(5):721-32. PubMed PMID: 22078797; PMCID: PMC3230302.
  24. Arpaia N, Godec J, Lau L, Sivick KE, McLaughlin LM, Jones MB, Dracheva T, Peterson SN, Monack DM, Barton GM. TLR signaling is required for Salmonella typhimurium virulence. Cell. 2011;144(5):675-88. PubMed PMID: 21376231; PMCID: PMC3063366.

For a complete list of publications, please visit PubMed.gov