Research

noimageprofileResearch in our laboratory focuses on mechanisms underlying the regulation of gene expression and how these mechanisms are disrupted in neurodegenerative diseases. We use high-throughput functional genomics and genetic association studies to identify regions of the genome with functional effects on tissues and cells of the brain. We apply methods from statistical and population genetics to large-scale genotyping and sequencing studies to discover novel susceptibility alleles for age-related cognitive decline and Alzheimer’s disease. We collaborate extensively with colleagues to develop and apply methods for constructing causal regulatory networks to understand mechanisms driving complex diseases. Our work is primarily computational, with an emphasis on integrative data analysis and the development of statistical and computational approaches, but we often work closely with experimental biologists.

Contact Us

Raj Laboratory
Towfique Raj, PhD
Assistant Professor, Neuroscience
Assistant Professor, Genetics and Genomic Sciences
Assistant Professor, Neurology
Location
Lab: ICAHN 10-52
Email

Featured

Featured Publication

Global and local ancestry in African-Americans: Implications for Alzheimer’s disease risk.
Hohman TJ, Cooke-Bailey JN, Reitz C, Jun G, Naj A, Beecham GW, Liu Z, Carney RM, Vance JM, Cuccaro ML, Rajbhandary R, Vardarajan BN, Wang LS, Valladares O, Lin CF, Larson EB, Graff-Radford NR, Evans D, De Jager PL, Crane PK, Buxbaum JD, Murrell JR, Raj T, et al. Alzheimers Dement. 2016 Mar;12(3):233-43. doi: 10.1016/j.jalz.2015.02.012. Epub 2015 Jun 16.

African-American (AA) individuals have a higher risk for late-onset Alzheimer’s disease (LOAD) than Americans of primarily European ancestry (EA).

Publications

2015

Hohman TJ, Cooke-Bailey JN, Reitz C, Jun G, Naj A, Beecham GW, Liu Z, Carney RM, Vance JM, Cuccaro ML, Rajbhandary R, Vardarajan BN, Wang LS, Valladares O, Lin CF, Larson EB, Graff-Radford NR, Evans D, De Jager PL, Crane PK, Buxbaum JD, Murrell JR, Raj T, Ertekin-Taner N, Logue MW, Baldwin CT, Green RC, Barnes LL, Cantwell LB, Fallin MD, Go RC, Griffith P, Obisesan TO, Manly JJ, Lunetta KL, Kamboh MI, Lopez OL, Bennett DA, Hardy J, Hendrie HC, Hall KS, Goate AM, Lang R, Byrd GS, Kukull WA, Foroud TM, Farrer LA, Martin ER, Pericak-Vance MA, Schellenberg GD, Mayeux R, Haines JL, Thornton-Wells TA; Alzheimer Disease Genetics Consortium. Global and local ancestry in African-Americans: Implications for Alzheimer’s disease risk. Alzheimers Dement. 2015 Jun 16. pii: S1552-5260(15)00190-9. PMID: 26092349


Sul JH, Raj T, de Jong S, de Bakker PI, Raychaudhuri S, Ophoff RA, Stranger BE, Eskin E, Han B. Accurate and Fast Multiple-Testing Correction in eQTL Studies. Am J Hum Genet. 2015 Jun 4;96(6):857-68. PMID: 26027500


Tilburgs T, Crespo AC, van der Zwan A, Rybalov B, Raj T, Stranger B, Gardner L, Moffett A, Strominger JL. Human HLA-G+ extravillous trophoblasts: Immune-activating cells that interact with decidual leukocytes. Proc Natl Acad Sci U S A. 2015 Jun 9;112(23):7219-24. PMID: 26015573


Esposito F, Sorosina M, Ottoboni L, Lim ET, Replogle JM, Raj T, Brambilla P, Liberatore G, Guaschino C, Romeo M, Pertel T, Stankiewicz JM, Martinelli V, Rodegher M, Weiner HL, Brassat D, Benoist C, Patsopoulos NA, Comi G, Elyaman W, Martinelli Boneschi F, De Jager PL. A pharmacogenetic study implicates SLC9a9 in multiple sclerosis disease activity. Ann Neurol. 2015 Jul;78(1):115-27. Epub 2015 May 14. PMID: 25914168


Replogle JM, Chan G, White CC, Raj T, Winn PA, Evans DA, Sperling RA, Chibnik LB, Bradshaw EM, Schneider JA, Bennett DA, De Jager PL. A TREM1 variant alters the accumulation of Alzheimer-related amyloid pathology. Ann Neurol. 2015 Mar;77(3):469-77. PMID: 25545807

2014

De Jager PL, Srivastava G, Lunnon K, Burgess J, Schalkwyk LC, Yu L, Eaton ML, Keenan BT, Ernst J, McCabe C, Tang A, Raj T, Replogle J, Brodeur W, Gabriel S, Chai HS, Younkin C, Younkin SG, Zou F, Szyf M, Epstein CB, Schneider JA, Bernstein BE, Meissner A, Ertekin-Taner N, Chibnik LB, Kellis M, Mill J, Bennett DA. Alzheimer’s disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci. Nat Neurosci. 2014 Sep;17(9):1156-63. PMID: 25129075


Ye CJ, Feng T, Kwon HK, Raj T, Wilson MT, Asinovski N, McCabe C, Lee MH, Frohlich I, Paik HI, Zaitlen N, Hacohen N, Stranger B, De Jager P, Mathis D, Regev A, Benoist C. Intersection of population variation and autoimmunity genetics in human T cell activation. Science. 2014 Sep 12;345(6202):1254665. PMID: 25214635


Hu X, Kim H, Raj T, Brennan PJ, Trynka G, Teslovich N, Slowikowski K, Chen WM, Onengut S, Baecher-Allan C, De Jager PL, Rich SS, Stranger BE, Brenner MB, Raychaudhuri S. Regulation of gene expression in autoimmune disease loci and the genetic basis of proliferation in CD4+ effector memory T cells. PLoS Genet. 2014 Jun 26;10(6):e1004404. PMID: 24968232


Raj T, Rothamel K, Mostafavi S, Ye C, Lee M, Replogle JM, Feng T, Lee M, Asinovski N, Frohlich I, Imboya S, Von Korff A, Okada Y, Patsopoulos NA, Davis S, McCabe C, Paik H, Srivastava GP, Raychaudhuri S, Hafler DA, Koller D, Regev A, Hacohen N, Mathis D, Benoist C, Stranger BE, De Jager PL. Polarization of the Effects of Autoimmune and Neurodegenerative Risk Alleles in Leukocytes. Science. 2014 May 2;344(6183):519-23. PMID: 24786080


Lee MN, Ye C, Villani AC, Raj T, Li W, Eisenhaure TM, Imboywa SH, Chipendo PI, Ran FA, Slowikowski K, Ward LD, Raddassi K, McCabe C, Lee MH, Frohlich IY, Hafler DA, Kellis M, Raychaudhuri S, Zhang F, Stranger BE, Benoist CO, De Jager PL, Regev A, Hacohen N. Common genetic variants modulate pathogen-sensing responses in human dendritic cells. Science. 2014;343(6175):1246980. PMID: 24604203


Ferraro A, D’Alise AM, Raj T, Asinovski N, Phillips R, Ergun A, Replogle JM, Bernier A, Laffel L, Stranger BE, De Jager PL, Mathis D, Benoist C. Interindividual variation in human T regulatory cells. Proc Natl Acad Sci U S A. 2014 Mar 25;111(12):E1111-20. PMID: 24610777


Hutchinson JN, Raj T, Fagerness J, Stahl E, Viloria F, Gimelbrant A, Seddon J, Daly M, Chess A and Plenge R. Alelle Specific Methylation Occurs at Genetic Variants Associated with Complex Disease. PLoS One. 2014 Jun 9;9(6):e98464. PMID: 24911414


Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K, Kochi Y, Ohmura K, Suzuki A, Yoshida S, Graham RR, Manoharan A, Ortmann W, Bhangale T, Denny JC, Carroll RJ, Eyler AE, Greenberg JD, Kremer JM, Pappas DA, Jiang L, Yin J, Ye L, Su DF, Yang J, Xie G, Keystone E, Westra HJ, Esko T, Metspalu A, Zhou X, Gupta N, Mirel D, Stahl EA, Diogo D, Cui J, Liao K, Guo MH, Myouzen K, Kawaguchi T, Coenen MJ, van Riel PL, van de Laar MA, Guchelaar HJ, Huizinga TW, Dieudé P, Mariette X, Bridges SL Jr, Zhernakova A, Toes RE, Tak PP, Miceli-Richard C, Bang SY, Lee HS, Martin J, Gonzalez-Gay MA, Rodriguez-Rodriguez L, Rantapää-Dahlqvist S, Arlestig L, Choi HK, Kamatani Y, Galan P, Lathrop M; RACI consortium; GARNET consortium, Eyre S, Bowes J, Barton A, de Vries N, Moreland LW, Criswell LA, Karlson EW, Taniguchi A, Yamada R, Kubo M, Liu JS, Bae SC, Worthington J, Padyukov L, Klareskog L, Gregersen PK, Raychaudhuri S, Stranger BE, De Jager PL, Franke L, Visscher PM, Brown MA, Yamanaka H, Mimori T, Takahashi A, Xu H, Behrens TW, Siminovitch KA, Momohara S, Matsuda F, Yamamoto K, Plenge RM. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature. 2014;506(7488):376-81. PMID: 24390342


Raj T, Ryan KJ, Replogle JM, Chibnik LB, Rosenkrantz L, Tang A, Rothamel K, Stranger BE, Bennett DA, Evans DA, De Jager PL, Bradshaw EM. CD33: increased inclusion of exon 2 implicates the Ig V-set domain in Alzheimer’s disease susceptibility. Hum Mol Genet. 2014 May 15;23(10):2729-36. PMID: 24381305


Okada Y, Diogo D, Greenberg JD, Mouassess F, Achkar WA, Fulton RS, Denny JC, Gupta N, Mirel D, Gabriel S, Li G, Kremer JM, Pappas DA, Carroll RJ, Eyler AE, Trynka G, Stahl EA, Cui J, Saxena R, Coenen MJ, Guchelaar HJ, Huizinga TW, Dieudé P, Mariette X, Barton A, Canhão H, Fonseca JE, de Vries N, Tak PP, Moreland LW, Bridges SL Jr, Miceli-Richard C, Choi HK, Kamatani Y, Galan P, Lathrop M, Raj T, De Jager PL, Raychaudhuri S, Worthington J, Padyukov L, Klareskog L, Siminovitch KA, Gregersen PK, Mardis ER, Arayssi T, Kazkaz LA, Plenge RM. (2014) Integration of Sequence Data from a Consanguineous Family with Genetic Data from an Outbred Population Identifies PLB1 as a Candidate Rheumatoid Arthritis Risk Gene. PLoS One 9:e87645. PMID: 24520335

2013

Reitz C, Mayeux R, and Alzheimer’s Disease Genetics Consortium (Raj T). TREM2 and neurodegenerative disease. N Engl J Med. 2013;369(16):1564-5. PMID: 24278027


Patsopoulos NA, Barcellos LF, Hintzen RQ, Schaefer C, van Duijn CM, Noble JA, Raj T, Gourraud P-A, Stranger BE, Oksenberg J, et al. Fine-mapping the genetic association of the major histocompatibility complex in multiple sclerosis: HLA and non-HLA effects. PLoS Genet. 2013;9(11):e1003926.


Bradshaw EM, Chibnik LB, Keenan BT, Ottoboni L, Raj T, Tang A, Rosenkrantz LL, Imboywa S, Lee M, Von Korff A; Alzheimer Disease Neuroimaging Initiative, Morris MC, Evans DA, Johnson K, Sperling RA, Schneider JA, Bennett DA, De Jager PL. CD33 Alzheimer’s disease locus: altered monocyte function and amyloid biology. Nat Neurosci. 2013. 16:848-50. PMID: 23708142


Cui J, Stahl EA, Saevarsdottir S, Miceli C, Diogo D, Trynka G, Raj T, Mirkov MU, Canhao H, Ikhari K, Terao C, Okada Y, Wedren S, Askling J, Yamanaka H, Momohara S, Taniguchi A, Ohmura K, Matsuda F, Mimori Ti, Gupta N, Kuchroo M, Morgan AW, Isaacs JD, Wilson AG, Hyrich KL, Herenius M, Doorenspleet ME, Tak PP, Crusius JB, van der Horst-Bruinsma IE, Wolbink GJ, van Riel PL, van de Laar M, Guchelaar HJ, Shadick NA, Allaart CF, Huizinga TW, Toes RE, Kimberly RP, Bridges SL Jr, Criswell LA, Moreland LW, Fonseca JE, de Vries N, Stranger BE, De Jager PL, Raychaudhuri S, Weinblatt ME, Gregersen PK, Mariette X, Barton A, Padyukov L, Coenen MJ, Karlson EW, Plenge RM. (2013) Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis. PLoS Genet. 9:e1003394. PMID: 23555300


Raj T, Kuchroo M, Replogle JM, Raychaudhuri S, Stranger BE, De Jager PL. Common risk alleles for inflammatory diseases are targets of recent positive selection. Am J Hum Genet. 2013;92(4):517-29. PMID: 23522783


Reitz C, Jun G, Naj A, Rajbhandary R, Vardarajan BN, Wang LS, Valladares O, Lin CF, Larson EB, Graff-Radford NR, Evans D, De Jager PL, Crane PK, Buxbaum JD, Murrell JR, Raj T, Ertekin-Taner N, Logue M, Baldwin CT, Creen RC, Barnes LL, Cantwell LB, Fallin MD, Go RC, Griffith P, Obisesan TO, Manly JJ, Lunetta KL, Kamboh MI, Lopez OL, Bennett DA, Hendrie H, Hall KS, Goate AM, Byrd GS, Kukull WA, Foroud TM, Haines JL, Farrer LA, Pericak-Vance MA, Schellenberg GD, Mayeux R; Alzheimer Disease Genetics Consortium. Variants in the ATP-binding cassette transporter (ABCA7), apolioprotein E ϵ4, and the risk of late-onset Alzheimer disease in African Americans. JAMA 2013. 309:1483-92. PMID: 23571587

Gokcumen O, Zhu Q, Mulder LCF, Iskow RC, Austermann C, Scharer CD, Raj T, Boss JM, Sunyaev S, Price A, et al. Balancing selection on a regulatory region exhibiting ancient variation that predates human-neandertal divergence. PLoS Genet. 2013;9(4):e1003404. PMID: 23593015


Stranger BE, Raj T. Genetics of human gene expression. Curr Opin Genet Dev. 2013;23(6):627-34. PMID: 24238872


Mode CJ, Sleeman CK, Raj T. On the inclusion of self regulating branching processes in the working paradigm of evolutionary and population genetics. Front Genet. 2013;4:11. PMID: 23424044

2012

Lim ASP, Chang A-M, Shulman JM, Raj T, Chibnik LB, Cain SW, Rothamel K, Benoist C, Myers AJ, Czeisler CA, et al. A common polymorphism near PER1 and the timing of human behavioral rhythms. Ann Neurol. 2012;72(3):324-34. PMID: 23034908


Keenan BT, Shulman JM, Chibnik LB, Raj T, Tran D, Sabuncu MR, Allen AN, Corneveaux JJ, Hardy JA, Huentelman MJ, et al. A coding variant in CR1 interacts with APOE-ε4 to influence cognitive decline. Hum Mol Genet. 2012;21(10):2377-88. PMID: 22343410


De Jager PL, Shulman JM, Chibnik LB, Keenan BT, Raj T, Wilson RS, Yu L, Leurgans SE, Tran D, Aubin C, et al. A genome-wide scan for common variants affecting the rate of age-related cognitive decline. Neurobiol Aging. 2012;33(5):1017.e1-15. PMID: 22054870


Brown KH, Dobrinski KP, Lee AS, Gokcumen O, Mills RE, Shi X, Chong WW, Chen JY, Yoo P, David S, Peterson SM, Raj T, Choy KW, Stranger BE, Williamson RE, Zon LI, Freeman JL, Lee C. Extensive genetic diversity and substructuring among zebrafish strains revealed through copy number variant analysis. Proc Natl Acad Sci U S A. 2012;109(2):529-34. PMID: 22203992


Dimas AS, Nica AC, Montgomery SB, Stranger BE, Raj T, Buil A, Giger T, Lappalainen T, Gutierrez-Arcelus M, McCarthy MI, et al. Sex-biased genetic effects on gene regulation in humans. Genome Res. 2012;22(12):2368-75. PMID: 22960374


Raj T, Shulman JM, Keenan BT, Chibnik LB, Evans DA, Bennett DA, Stranger BE, De Jager PL. Alzheimer disease susceptibility loci: evidence for a protein network under natural selection. Am J Hum Genet. 2012;90(4):720-6. PMID: 22482808


Stranger BE, Montgomery SB, Dimas AS, Parts L, Stegle O, Ingle CE, Sekowska M, Smith GD, Evans D, Gutierrez-Arcelus M, Price A, Raj T, Nisbett J, Nica AC, Beazley C, Durbin R, Deloukas P, Dermitzakis ET. Patterns of cis regulatory variation in diverse human populations. PLoS Genet. 2012;8(4):e1002639. PMID: 22532805

2011

Stranger BE, Stahl EA, Raj T. Progress and promise of genome-wide association studies for human complex trait genetics. Genetics. 2011;187(2):367-83. PMID: 21115973


Qutob N, Balloux F, Raj T, Liu H, Marion de Procé S, Trowsdale J, Manica A. Signatures of historical demography and pathogen richness on MHC class I genes. Immunogenetics. 2011;64(3):165-75. PMID: 21947542

2004

Murphy K, Raj T, Winters SR, White PS. me-PCR: a refined ultrafast algorithm for identifying sequence-defined genomic elements. Bioinformatics. 2004;20(4):588-90. PMID: 14990458


Kong X, Murphy K, Raj T, He C, White PS, Matise TC. A combined linkage-physical map of the human genome. Am J Hum Genet. 2004;75(6):1143-8. PMID: 15486828