Center for Computational and Integrative Biology
Center for Computational & Integrative Biology
185 Cambridge Street - Simches 7222
Boston, MA 02114
Senior Associate Member
Broad Institute of Harvard and MIT
7 Cambridge Center, 5th floor (lab and office)
Cambridge, MA 02142
Visit my lab page here.
The overall goal in the laboratory is to discover and understand the function of important mediators and effectors involved in innate (autophagy, pathogen containing vacuole) and adaptive (T cell activation) immunity. Especially of interest are the cellular components and regulatory networks which interact dynamically within temporal, spatial and patho-physiological contexts of innate immunity. We are pursuing integrative systems approaches that closely couple genome-wide experimentation with high throughput assays (RNAi and cDNA screens) and computational methods. Using these approaches we are interested in addressing the following questions 1) what are the mechanisms by which autophagy regulates innate and adaptive immunity 2) the role of NOD/LRR domains in sensing microbial effectors 3) how are innate immune pathways dysregulated in mucosal immunity. The adaptive immunity program focuses elucidating signal transduction pathways coordinated by the CARMA/Dlg family of scaffold proteins.
Among complex diseases, genetics has been particularly successful in the identification of genes for IBD with recent efforts in genome-wide association studies bringing the total number of genes to >60. These studies have highlighted the significance of the relationship between intracellular responses to microbes and the regulation of adaptive immunity in the pathogenesis of IBD. With the rapid progress in human genetics it has become clear that a major challenge in the study of complex genetic traits is to determine how disease genes and their corresponding alleles exert their influence on the biology of health and disease. The lab focuses on applying novel genomic, genetic and chemical biology approaches to gain insights into the function of genetic variants underlying common inflammatory disease and to explore the potential for reversing the effects of susceptibility alleles.
Smeekens SP, Ng A, Kumar V, Johnson MD, Plantinga TS, van Diemen C, Arts P, Verwiel ETP, Gresnigt MS, Fransen K, van Sommeren S, Oosting M, Cheng S-C, Joosten LAB, Hoischen A, Kullberg B-J, Scott WK, Perfect JR, van der Meer JWM, Wijmenga C, Netea MG, Xavier RJ. 2012. Functional genomics identifies type 1 interferon pathway as central for host defense against Candida albicans. Nat Commun. In press. DOI: 10.1038/ncomms2343.
Huett A, Heath RJ, Begun J, Sassi SO, Baxt LA, Vyas JM, Goldberg MB, Xavier RJ. The LRR and RING Domain Protein LRSAM1 Is an E3 Ligase Crucial for Ubiquitin-Dependent Autophagy of Intracellular Salmonella Typhimurium. Cell Host Microbe. 2012;12(6):778-90. PMID: 23245322.
Conway KL, Goel G, Sokol H, Manocha M, Mizoguchi E, Terhorst C, Bhan AK, Gardet A, Xavier RJ. p40phox expression regulates neutrophil recruitment and function during the resolution phase of intestinal inflammation. J Immunol. 2012;189(7):3631-40. PMID: 22914050.
Rivas MA, Beaudoin M, Gardet A, Stevens C, Sharma Y, Zhang CK, Boucher G, Ripke S, Ellinghaus D, Burtt N, Fennell T, Kirby A, Latiano A, Goyette P, Green T, Halfvarson J, Haritunians T, Korn JM, Kuruvilla F, Lagace C, Neale B, Lo KS, Schumm P, Torkvist L, Dubinsky MC, Brant SR, Silverberg MS, Duerr RH, Altshuler D, Gabriel S, Lettre G, Franke A, D'Amato M, McGovern DP, Cho JH, Rioux JD, Xavier RJ, Daly MJ. Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease. Nat Genet. 2011;43(11):1066-73. PMID: 21983784.
Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature. 2011;474(7351):307-17. PMID: 21677747.
Last Update: 1/4/2013