John Ray, PhD
Background Information
John Ray received his BS in Molecular, Cellular and Development Biology at the University of Washington in 2007 and his PhD in Immunobiology at Yale University in 2014, working in the laboratory of Joe Craft, MD. He completed postdoctoral research at the Broad Institute of MIT and Harvard University in the lab of Nir Hacohen, PhD, studying autoimmune-associated genetic variants and epigenetic regulation in immune cell subsets in order to better understand the mechanism for risk at specific loci and global transcriptional deregulation in those susceptible to autoimmunity. Dr. Ray joined the faculty of the Benaroya Research Institution in 2020 and is currently an Assistant Member.
Area of Research
The Ray lab studies the mechanisms that contribute to variation in human immune responses. In particular, we determine how genetic variants and non-coding regulatory regions alter immune responses and confer autoimmune disease susceptibility. With a focus on T cells, we prioritize likely disease-causal genetic variants and enhancers, and, in human and mouse systems, we dissect their mechanisms of action. Understanding the mechanisms of inherited autoimmune disease susceptibility will inform efforts for personalized therapies and disease prevention.
Featured Publications
Mouri K, Guo MH, de Boer CG, Lissner MM, Harten IA, Newby GA, DeBerg HA, Platt WF, Gentili M, Liu DR, Campbell DJ, Hacohen N, Tewhey R, Ray JP. Prioritization of autoimmune disease-associated genetic variants that perturb regulatory element activity in T cells. Nat Genet. 2022 May 5. doi: 10.1038/s41588-022-01056-5. PMID: 35513721
Dahlqvist J, Fulco CP, Ray JP, Liechti T, de Boer CG, Lieb DJ, Eisenhaure TM, Engreitz JM, Roederer M, Hacohen N. Systematic identification of genomic elements that regulate FCGR2A expression and harbor variants linked with autoimmune disease. Hum Mol Genet. 2021 Dec 31:ddab372. doi: 10.1093/hmg/ddab372. PMID: 34970970
Nasser J, Bergman DT, Fulco CP, Guckelberger P, Doughty BR, Patwardhan TA, Jones TR, Nguyen TH, Ulirsch JC, Lekschas F, Mualim K, Natri HM, Weeks EM, Munson G, Kane M, Kang HY, Cui A, Ray JP, Eisenhaure TM, Collins RL, Dey K, Pfister H, Price AL, Epstein CB, Kundaje A, Xavier RJ, Daly MJ, Huang H, Finucane HK, Hacohen N, Lander ES, Engreitz JM. Genome-wide enhancer maps link risk variants to disease genes. Nature. 2021 May;593(7858):238-243. doi: 10.1038/s41586-021-03446-x. PMID: 33828297
Lu X, Chen X, Forney C, Donmez O, Miller D, Parameswaran S, Hong T, Huang Y, Pujato M, Cazares T, Miraldi ER, Ray JP, de Boer CG, Harley JB, Weirauch MT, Kottyan LC. Global discovery of lupus genetic risk variant allelic enhancer activity. Nat Commun. 2021 Mar 12;12(1):1611. doi: 10.1038/s41467-021-21854-5. PMID: 33712590 | PMC7955039
de Boer CG, Ray JP, Hacohen N, Regev A. MAUDE: inferring expression changes in sorting-based CRISPR screens. Genome Biol. 2020 Jun 3;21(1):134. doi: 10.1186/s13059-020-02046-8. PMID: 32493396 | PMC7268349
Ray JP, de Boer CG, Fulco CP, Lareau CA, Kanai M, Ulirsch JC, Tewhey R, Ludwig LS, Reilly SK, Bergman DT, Engreitz JM, Issner R, Finucane HK, Lander ES, Regev A, Hacohen N. Prioritizing disease and trait causal variants at the TNFAIP3 locus using functional and genomic features. Nat Commun. 2020 Mar 6;11(1):1237. doi: 10.1038/s41467-020-15022-4. PMID: 32144282 | PMC7060350
Sade-Feldman M, Yizhak K, Bjorgaard SL, Ray JP, de Boer CG, Jenkins RW, Lieb DJ, Chen JH, Frederick DT, Barzily-Rokni M, Freeman SS, Reuben A, Hoover PJ, Villani AC, Ivanova E, Portell A, Lizotte PH, Aref AR, Eliane JP, Hammond MR, Vitzthum H, Blackmon SM, Li B, Gopalakrishnan V, Reddy SM, Cooper ZA, Paweletz CP, Barbie DA, Stemmer-Rachamimov A, Flaherty KT, Wargo JA, Boland GM, Sullivan RJ, Getz G, Hacohen N. Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma. Cell. 2018 Nov 1;175(4):998-1013.e20. doi: 10.1016/j.cell.2018.10.038. Erratum in: Cell. 2019 Jan 10;176(1-2):404. PMID: 30388456 | PMC6641984
Grossman SR, Engreitz J, Ray JP, Nguyen TH, Hacohen N, Lander ES. Positional specificity of different transcription factor classes within enhancers. Proc Natl Acad Sci U S A. 2018 Jul 24;115(30):E7222-E7230. doi: 10.1073/pnas.1804663115. Epub 2018 Jul 9. PMID: 29987030 | PMC6065035
Sade-Feldman M, Jiao YJ, Chen JH, Rooney MS, Barzily-Rokni M, Eliane JP, Bjorgaard SL, Hammond MR, Vitzthum H, Blackmon SM, Frederick DT, Hazar-Rethinam M, Nadres BA, Van Seventer EE, Shukla SA, Yizhak K, Ray JP, Rosebrock D, Livitz D, Adalsteinsson V, Getz G, Duncan LM, Li B, Corcoran RB, Lawrence DP, Stemmer-Rachamimov A, Boland GM, Landau DA, Flaherty KT, Sullivan RJ, Hacohen N. Resistance to checkpoint blockade therapy through inactivation of antigen presentation. Nat Commun. 2017 Oct 26;8(1):1136. doi: 10.1038/s41467-017-01062-w. PMID: 29070816 | PMC5656607
Ray JP, Staron MM, Shyer JA, Ho PC, Marshall HD, Gray SM, Laidlaw BJ, Araki K, Ahmed R, Kaech SM, Craft J. The Interleukin-2-mTORc1 Kinase Axis Defines the Signaling, Differentiation, and Metabolism of T Helper 1 and Follicular B Helper T Cells. Immunity. 2015 Oct 20;43(4):690-702. doi: 10.1016/j.immuni.2015.08.017. Epub 2015 Sep 22. PMID: 26410627 | PMC4618086
Marshall HD, Ray JP, Laidlaw BJ, Zhang N, Gawande D, Staron MM, Craft J, Kaech SM. The transforming growth factor beta signaling pathway is critical for the formation of CD4 T follicular helper cells and isotype-switched antibody responses in the lung mucosa. Elife. 2015 Jan 8;4:e04851. doi: 10.7554/eLife.04851. PMID: 25569154 | PMC4337607
Ray JP, Marshall HD, Laidlaw BJ, Staron MM, Kaech SM, Craft J. Transcription factor STAT3 and type I interferons are corepressive insulators for differentiation of follicular helper and T helper 1 cells. Immunity. 2014 Mar 20;40(3):367-77. doi: 10.1016/j.immuni.2014.02.005. Epub 2014 Mar 13. PMID: 24631156; PMCID: PMC3992517.
Tobin DM, Roca FJ, Ray JP, Ko DC, Ramakrishnan L. An enzyme that inactivates the inflammatory mediator leukotriene b4 restricts mycobacterial infection. PLoS One. 2013 Jul 11;8(7):e67828. doi: 10.1371/journal.pone.0067828. PMID: 23874453 | PMC3708926
Tobin DM, Roca FJ, Oh SF, McFarland R, Vickery TW, Ray JP, Ko DC, Zou Y, Bang ND, Chau TT, Vary JC, Hawn TR, Dunstan SJ, Farrar JJ, Thwaites GE, King MC, Serhan CN, Ramakrishnan L. Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections. Cell. 2012 Feb 3;148(3):434-46. doi: 10.1016/j.cell.2011.12.023. PMID: 22304914 | PMC3433720
Tobin DM, Vary JC Jr, Ray JP, Walsh GS, Dunstan SJ, Bang ND, Hagge DA, Khadge S, King MC, Hawn TR, Moens CB, Ramakrishnan L. The lta4h locus modulates susceptibility to mycobacterial infection in zebrafish and humans. Cell. 2010 Mar 5;140(5):717-30. doi: 10.1016/j.cell.2010.02.013. PMID: 20211140 | PMC2907082
Kacar T, Ray JP, Gungormus M, Emre Oren E, Tamerler C, Sarikaya M. Quartz Binding Peptides as Molecular Linkers towards Fabricating Multifunctional Micropatterned Substrates. Advanced Materials 2009 Jan 12; doi:10.1002/adma.200801877