John P. Ray, PhD

Dr. Ray received his PhD in Immunobiology at Yale University in 2014. He completed his postdoctoral fellowship at the Broad Institute of MIT and Harvard in 2020 and then joined the faculty of the Benaroya Research Institution as an Assistant Member.

RESEARCH

Autoimmune diseases have complex genetic etiologies. If we had a better understanding of the genetic drivers of these diseases, we would be better able to diagnose, treat, and prevent disease. Genome-wide association studies (GWAS) have led to the discovery of hundreds of disease-associated loci across the genome. However, identifying the actual disease-causal genetic variants is difficult because the vast majority are in non-coding regions, and because these variants are often tightly correlated with non-disease causal variants.

We are focused on understanding how these non-coding genetic variants regulate immune and autoimmune responses. Using a mixture of traditional immunology, genetics, and functional genomics, our goal is to elucidate the biochemical mechanism of disease-causal non-coding variants and their consequences on T cell differentiation, function, and dysregulation in mice and humans.

PUBLICATIONS

1. 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; 54(5):603-612.
2. 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. In press, 2021 Dec 31:ddab372. doi: 10.1093/hmg/ddab372
3. Nasser J, Bergman DT, Fulco CP, Guckelberger P, Doughty BR, Patwardhan T, Jones TR, Nguyen TH, Ulirsch JC, Natri HM, Weeks EM, Munson G, Kane M, Kang HY, Cui A, Ray JP, Eisenhaure TM, Mualim K, Collins RL, Dey K, Price AL, Epstein CB, Kundaje A, Xavier RJ, Daly MJ, Huang H, Finucane HK, Hacohen N, Lander ES, Engreitz JM. Genome-wide maps of enhancer regulation connect risk variants to genes. Nature. 2021; 593(7858):238-243.  PMC Journal – In Process
4. Lu X, Chen X, Foreny 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; 12(1):1611.  PMC7955039
   
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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
13. 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