Crohn’s Disease and Ulcerative Colitis
Steven Ross Brant, M.D.
Lisa Wu Datta, M.S., research associate
Chengrui Huang, Ph.D., postdoctoral fellow, statistical genetics
Miquel Alfonso Ramos, M.D., postdoctoral fellow
George Salem, M.D., postdoctoral fellow
Denise Spears, B.A., senior study coordinator
Patricia Ushry, CMA, senior recruitment specialist
Yuqiong Wu, M.D., laboratory manager
Abdel Hamad, Ph.D., associate professor of pathology
Wen Hong (Linda) Kao, Ph.D., associate professor of epidemiology
Susan Hutfless, Ph.D., instructor, department of medicine
Xuhang Li, Ph.D., associate professor of medicine
Andy McCallion, Ph.D., associate professor of genetics
Yin Yao, M.P.H., Ph.D., adjunct associate professor of medicine
The primary focus of our lab is the role of genetic variation in etiopathogenesis, disease manifestations and disease course in inflammatory bowel disease (IBD), Crohn’s disease and ulcerative colitis.
Our laboratory is one of the six genetics research centers, funded since 2002, of the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) IBD Genetics Consortium and is a collaborating center of the International IBD Genetics Consortium (IIBDGC). We are providing resources to both consortia by recruitment of patients with IBD and matched controls, with a particular focus on familial IBD, as well as in the African-American and Ashkenazi Jewish populations.
Our laboratory is identifying and characterizing susceptibility genes for IBD in the African-American population by candidate gene and genome-wide association mapping studies. We are evaluating the effect of these genes on disease phenotype and disease course and also evaluating racial disparity in medical care. We are identifying genes for familial IBD in multiple affected families, particularly those of Ashkenazi Jewish ancestry, by genome-wide linkage, genome-wide association mapping and whole genome sequencing. We are determining which gene variations associated with IBD in non-coding regions of the genome cause IBD by modifying gene expression, and we are characterizing the epigenome regulation of IBD risk genes in cells key to IBD pathogenesis.
In a project funded by the Department of Defense, we are investigating occurrence of infectious diseases, as determined by sero-conversion, “triggering” Crohn’s disease, in genetically susceptible individuals. We are also investigating the role of vitamin D and genetic modifiers of vitamin D as causing Crohn’s disease. We are evaluating evidence for gene X gene interactions and gene X microbial interactions leading to IBD onset and variations in disease course. We are evaluating the cause of side effects of medications treating IBD, in collaboration with the IIBDGC, with a particular focus on genetic determinants of skin disease as a consequence of IBD-related therapy.
- Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A, Green T, Kuballa P, Barmada MM, Datta LW, Shugart YY, Griffiths AM, Targan SR, Ippoliti AF, Bernard EJ, Mei L, Nicolae DL, Regueiro M, Schumm LP, Steinhart AH, Rotter JI, Duerr RH, Cho JH, Daly MJ, Brant SR. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet. 2007; 39:596-604
- Shugart YY, Silverberg MS, Duerr RH, Taylor KD, Wang MH, Zarfas K, Schumm LP, Bromfield G, Steinhart AH, Griffiths AM, Kane SV, Barmada MM, Rotter JI, Mei L, Bernstein CN, Bayless TM, Langelier D, Cohen A, Bitton A, Rioux JD, Cho JH, and Brant SR. An SNP linkage scan identifies significant Crohn’s disease loci on chromosomes 13q13.3 and, in Jewish families, on 1p35.2 and 3q29. Genes Immun. 2008; 9:161-167
- Okazaki T, Wang MH, Rawsthorne P, Sargent M, Datta LW, Shugart YY, Bernstein CN, Brant SR. Contributions of IBD5, IL23R, ATG16L1, and NOD2 to Crohn's disease risk in a population-based case-control study: Evidence of gene-gene interactions. Inflamm Bowel Dis. 2008; 14:1528-1541
- Dassopoulos T, Nguyen GC, Talor MV, Datta LW, Isaacs KL, Lewis JD, Gold MS, Valentine JF, Smoot DT, Harris ML, Oliva-Hemker M, Bayless TM, NIDDK IBD Genetics Consortium, Burek CL, and Brant SR. NOD2 mutations and Anti-saccharomyces antibodies are risk factors for Crohn's Disease in African Americans. Am J. Gastroenterol 2010; 105:378-86
- Nguyen GC, Laveist TA, Harris ML, Wang MH, Datta LW, Brant SR. Racial Disparities in Utilization of Specialist Care and Medications in Inflammatory Bowel Disease. Am J Gastroenterol. 2010; 105:2202-2208
- Brant SR. Update on the Heritability of Inflammatory Bowel Disease: The Importance of Twin Studies. Inflamm Bowel Dis. 2011; 17:1-5
- Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, Lee JC, Schumm LP, Yashoda S, Anderson CA, Essers J, Mitrovic M, Ning K, Cleynen I, Theatre E., Spain SL, Raychaudhuri S, Goyette P, Wei Z, Abraham C, Achkar JP, Ahmad T, Amininejad L, Ananthakrishnan AN, Andersen V, Andrews JM, Baidoo L, Balschun T, Bampton PA, Bitton A, Boucher G, Brand S, Buning C, Cohain A, Cichon S, D’Amato M, De Jong D, Devaney KL, Dubinsky M, Edwards C, Ellinghaus D, Ferguson LR, Franchimont D, Fransen K, Gearry R, Georges M, Gieger C, Glas J, Haritunians T, Hart A, Hawkey C, Hedl M, Hu X, Karlsen TH, Kupcinskas L, Kugathasan S, Latiano A, Laukens D, Lawrance IC, Lees CW, Louis E, Mahy G, Mansfield J, Morgan AR, Mowat C, Newman W, Palmieri O, Ponsioen CY, Potocnik U, Prescott NJ, Regueiro M, Rotter JI, Russell RK, Sanderson JD, Sans M, Satsang J, Schreiber S, Simms L, Sventoraityte J, Targan SR, Taylor KD, Tremelling M, Verspaget HW, DeVos M, Wijmenga C, Wilson DC, Winkelmann J, Xavier RJ, Zeissig S, Zhang CK, Zhao H, Silverberg MS, Annese V, Hakonarson H, Brant SR, Radford-Smith G, Mathew CG, Rioux JD, Schadt EE, Daly MJ, Franke A, Parkes M, Vermeire S, Barrett JC, Cho JH. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature, 2012; 491:119-124
- Wang M-H, Okazaki T, Kugathasan S, Cho JH, Isaacs K L., Lewis J, Smoot D, Valentine JF, Kader H, Ford J, Harris ML, Oliva-Hemker M, Cuffari C, Torbenson MS, Duerr RH, Silverberg M, Rioux JD, Taylor K, Nguyen G, Wu Y, Datta LW, Hooker S, Dassopoulos T, Kittles RA, Kao WH. Brant SR. Contribution of higher risk genes and European admixture to Crohn’s disease in African Americans. Inflamm Bowel Dis. 2013. In Press
- Lazarev M, Huang C, Bitton A, Cho JH, Duerr RH, McGovern DP, Proctor DD, Regueiro M, Rioux JD, Schumm PP, Taylor KD, Silverberg MS, Steinhart AH, Hutfless S, Brant SR. Relationship Between Proximal Crohn’s Disease Location and Disease Behavior and Surgery: A Cross-Sectional Study of the IBD Genetics Consortium. Am J Gastro, 2013, In Press
- Brant SR. Promises, delivery and challenges of inflammatory bowel disease risk gene discovery. Am J Gastro. 2013; In Press