Research Centers

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Xavier Laboratory

The primary research goal of the Xavier Laboratory is to discover and understand the function of important mediators and effectors involved in the innate and adaptive immune systems. Of particular interest are the cellular components and regulatory networks that interact dynamically within temporal, spatial, and pathophysiological contexts of innate immunity. Current themes of the lab include (1) systems biology of innate and adaptive immunity, (2) functional mapping of pathways associated with Crohn's disease, ulcerative colitis and diabetes, and (3) genetics of Crohn's disease, celiac disease and ulcerative colitis.

The primary research goal of the Xavier Laboratory at Massachusetts General Hospital is to discover and understand the function of important mediators and effectors involved in both the innate and adaptive immune systems. Of particular interest are the cellular components and regulatory networks that interact dynamically within temporal, spatial and pathophysiological contexts of innate immunity.

We are pursuing integrative systems approaches that closely couple genome-wide experimentation with high-throughput assays and computational methods.

Ramnik Xavier, M.D., Ph.D.
Associate Professor in Medicine
Harvard Medical School
Massachusetts General Hospital
Simches Research Building
Boston, MA 02114
Phone: 617-643-3331

Fax: 617-643-3328

Christine Becker, Ph.D.
Jacob Begun, M.D., Ph.D.
Zhifang Cao, M.Sc., D.Sc.
Adam Castoreno, Ph.D.
Kara Conway, Ph.D.
Kathy Devaney
John Gagnon, B.S.
Gautam Goel, Ph.D.
Daniel Graham, Ph.D.
Robert Heath, Ph.D.
Humberto Jijon, M.D., Ph.D.
Bernard Khor, M.D., Ph.D.
Ira Kim, Ph.D.
Aleksandar Kostic, Ph.D.
Kara Lassen, Ph.D.
Isabel Latorre, Ph.D.
Juan Liao, Ph.D.
Aiping Liu
Lea Medeiros, Ph.D.
Amanda Mok, S.B.
Tatsuro Murano, M.D., Ph.D. 
Kavitha Narayan, Ph.D.
Daniel O'Connell, Ph.D.
Geraldine Paulus, Ph.D.
Joanna Peloquin, M.D.
David Rodriguez Fuentes, S.B.
Caitlin Russell, B.S., M.S.
Lauren Sless, S.B.
Thomas Sundberg, Ph.D.
Harry Thomas, M.D.
Eduardo Villablanca, Ph.D.
Moran Yassour, Ph.D.

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. Of particular 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. What are the roles of NOD/LRR domains in sensing microbial effectors?
3. How are innate immune pathways dysregulated in mucosal immunity?

The adaptive immunity program focuses on the elucidation of signal transduction pathways coordinated by the CARMA/Dlg family of scaffold proteins.
Crohn’s disease and ulcerative colitis are debilitating inflammatory diseases of the gastrointestinal tract collectively known as inflammatory bowel diseases. 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 more than 40. 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 influences on the biology of health and disease. Our lab focuses on applying novel genomic, genetic, and chemical biology approaches to gain insights into the function of genetic variants underlying common inflammatory diseases and to explore the potential for reversing the effects of susceptibility alleles.
Systems biology approaches to understand human disease signaling networks
The discovery of important mediators and effectors involved in immunity requires a deeper exploration of how these function as integrated systems. Especially of interest are the cellular components and regulatory networks which interact dynamically within temporal, spatial and pathophysiological contexts. We are pursuing integrative systems approaches that closely couple genome-wide experimentation with bioinformatics and computational methods.

We hope to gain additional insights about the immune system in terms of the underlying interaction and regulatory networks that define functional modules at the host-pathogen interface. In addition the team of computational biologists and mathematicians in the group are developing testable models using information from genome-wide studies and high-throughput screens to gain insight into molecular mechanisms of autoimmune disorders.

 

 

  1. Vandussen KL, Liu TC, Li D, Towfic F, Modiano N, Winter R, Haritunians T, Taylor KD, Dhall D, Targan SR, Xavier RJ, McGovern DP, Stappenbeck TS. Genetic Variants Synthesize to Produce Paneth Cell Phenotypes that Define Subtypes of Crohn's Disease. Gastroenterology. 2013. PMID: 24076061.
  2. Ananthakrishnan AN, Oxford EC, Nguyen DD, Sauk J, Yajnik V, Xavier RJ. Genetic risk factors for Clostridium difficile infection in ulcerative colitis. Aliment Pharmacol Ther. 2013;38(5):522-30. PMID: 23848254.
  3. Sokol H, Conway KL, Zhang M, Choi M, Morin B, Cao Z, Villablanca EJ, Li C, Wijmenga C, Yun SH, Shi HN, Xavier RJ. Card9 mediates intestinal epithelial cell restitution, T-helper 17 responses, and control of bacterial infection in mice. Gastroenterology. 2013;145(3):591-601 e3. PMID: 23732773.
  4. Beaudoin M, Goyette P, Boucher G, Lo KS, Rivas MA, Stevens C, Alikashani A, Ladouceur M, Ellinghaus D, Torkvist L, Goel G, Lagace C, Annese V, Bitton A, Begun J, Brant SR, Bresso F, Cho JH, Duerr RH, Halfvarson J, McGovern DP, Radford-Smith G, Schreiber S, Schumm PL, Sharma Y, Silverberg MS, Weersma RK, Quebec IBDGC, Consortium NIG, International IBDGC, D'Amato M, Vermeire S, Franke A, Lettre G, Xavier RJ, Daly MJ, Rioux JD. Deep Resequencing of GWAS Loci Identifies Rare Variants in CARD9, IL23R and RNF186 That Are Associated with Ulcerative Colitis. PLoS Genet. 2013;9(9):e1003723. PMID: 24068945.
  5. Shaw SY, Tran K, Castoreno AB, Peloquin JM, Lassen KG, Khor B, Aldrich LN, Tan PH, Graham DB, Kuballa P, Goel G, Daly MJ, Shamji AF, Schreiber SL, Xavier RJ. Selective Modulation of Autophagy, Innate Immunity, and Adaptive Immunity by Small Molecules. ACS Chem Biol. 2013. PMID: 24168452.
  6. Knights D, Lassen KG, Xavier RJ. Advances in inflammatory bowel disease pathogenesis: linking host genetics and the microbiome. Gut. 2013;62(10):1505-10. PMID: 24037875.
  7. Begun J, Xavier RJ. Autophagy at the crossroads of metabolism and cellular defense. Curr Opin Gastroenterol. 2013;29(6):588-96. PMID: 24100719.
  8. Coffee EM, Faber AC, Roper J, Sinnamon MJ, Goel G, Keung L, Wang WV, Vecchione L, de Vriendt V, Weinstein BJ, Bronson RT, Tejpar S, Xavier RJ, Engelman JA, Martin ES, Hung KE. Concomitant BRAF and PI3K/mTOR blockade is required for effective treatment of BRAF(V600E) colorectal cancer. Clin Cancer Res. 2013;19(10):2688-98. PMID: 23549875.
  9. Lupfer C, Thomas PG, Anand PK, Vogel P, Milasta S, Martinez J, Huang G, Green M, Kundu M, Chi H, Xavier RJ, Green DR, Lamkanfi M, Dinarello CA, Doherty PC, Kanneganti TD. Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection. Nat Immunol. 2013;14(5):480-8. PMID: 23525089.
  10. Gmyrek GB, Graham DB, Sandoval GJ, Blaufuss GS, Akilesh HM, Fujikawa K, Xavier RJ, Swat W. Polarity gene discs large homolog 1 regulates the generation of memory T cells. Eur J Immunol. 2013;43(5):1185-94. PMID: 23436244.
  11. Buffen K, Oosting M, Mennens S, Anand PK, Plantinga TS, Sturm P, van de Veerdonk FL, van der Meer JW, Xavier RJ, Kanneganti TD, Netea MG, Joosten LA. Autophagy modulates Borrelia burgdorferi-induced production of interleukin-1beta (IL-1beta). J Biol Chem. 2013;288(12):8658-66. PMID: 23386602.
  12. Sandoval GJ, Graham DB, Bhattacharya D, Sleckman BP, Xavier RJ, Swat W. Cutting edge: cell-autonomous control of IL-7 response revealed in a novel stage of precursor B cells. J Immunol. 2013;190(6):2485-9. PMID: 23420891.
  13. Kirby A, Gnirke A, Jaffe DB, Baresova V, Pochet N, Blumenstiel B, Ye C, Aird D, Stevens C, Robinson JT, Cabili MN, Gat-Viks I, Kelliher E, Daza R, DeFelice M, Hulkova H, Sovova J, Vylet'al P, Antignac C, Guttman M, Handsaker RE, Perrin D, Steelman S, Sigurdsson S, Scheinman SJ, Sougnez C, Cibulskis K, Parkin M, Green T, Rossin E, Zody MC, Xavier RJ, Pollak MR, Alper SL, Lindblad-Toh K, Gabriel S, Hart PS, Regev A, Nusbaum C, Kmoch S, Bleyer AJ, Lander ES, Daly MJ. Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing. Nat Genet. 2013;45(3):299-303. PMID: 23396133.
  14. Smeekens SP, Huttenhower C, Riza A, van de Veerdonk FL, Zeeuwen PL, Schalkwijk J, van der Meer JW, Xavier RJ, Netea MG, Gevers D. Skin Microbiome Imbalance in Patients with STAT1/STAT3 Defects Impairs Innate Host Defense Responses. J Innate Immun. 2013. PMID: 23796786.
  15. Martin ES, Belmont PJ, Sinnamon MJ, Richard LG, Yuan J, Coffee EM, Roper J, Lee L, Heidari P, Lunt SY, Goel G, Ji X, Xie Z, Xie T, Lamb J, Weinrich SL, VanArsdale T, Bronson RT, Xavier RJ, Vander Heiden MG, Kan JL, Mahmood U, Hung KE. Development of a colon cancer GEMM-derived orthotopic transplant model for drug discovery and validation. Clin Cancer Res. 2013;19(11):2929-40. PMID: 23403635.
  16. Giallourakis CC, Benita Y, Molinie B, Cao Z, Despo O, Pratt HE, Zukerberg LR, Daly MJ, Rioux JD, Xavier RJ. Genome-wide analysis of immune system genes by expressed sequence Tag profiling. J Immunol. 2013;190(11):5578-87. PMID: 23616578.
  17. Bornigen D, Morgan XC, Franzosa EA, Ren B, Xavier RJ, Garrett WS, Huttenhower C. Functional profiling of the gut microbiome in disease-associated inflammation. Genome Med. 2013;5(7):65. PMID: 23906180.
  18. Cortez-Retamozo V, Etzrodt M, Newton A, Ryan R, Pucci F, Sio SW, Kuswanto W, Rauch PJ, Chudnovskiy A, Iwamoto Y, Kohler R, Marinelli B, Gorbatov R, Wojtkiewicz G, Panizzi P, Mino-Kenudson M, Forghani R, Figueiredo JL, Chen JW, Xavier R, Swirski FK, Nahrendorf M, Weissleder R, Pittet MJ. Angiotensin II drives the production of tumor-promoting macrophages. Immunity. 2013;38(2):296-308. PMID: 23333075.
  19. O'Rourke EJ, Kuballa P, Xavier R, Ruvkun G. omega-6 Polyunsaturated fatty acids extend life span through the activation of autophagy. Genes Dev. 2013;27(4):429-40. PMID: 23392608.
  20. Shoji-Kawata S, Sumpter R, Leveno M, Campbell GR, Zou Z, Kinch L, Wilkins AD, Sun Q, Pallauf K, MacDuff D, Huerta C, Virgin HW, Helms JB, Eerland R, Tooze SA, Xavier R, Lenschow DJ, Yamamoto A, King D, Lichtarge O, Grishin NV, Spector SA, Kaloyanova DV, Levine B. Identification of a candidate therapeutic autophagy-inducing peptide. Nature. 2013;494(7436):201-6. PMID: 23364696.
  21. He C, Wei Y, Sun K, Li B, Dong X, Zou Z, Liu Y, Kinch LN, Khan S, Sinha S, Xavier RJ, Grishin NV, Xiao G, Eskelinen EL, Scherer PE, Whistler JL, Levine B. Beclin 2 functions in autophagy, degradation of g protein-coupled receptors, and metabolism. Cell. 2013;154(5):1085-99. PMID: 23954414.
  22. Conway KL, Kuballa P, Song JH, Patel KK, Castoreno AB, Yilmaz OH, Jijon HB, Zhang M, Aldrich LN, Villablanca EJ, Peloquin JM, Goel G, Lee IA, Mizoguchi E, Shi HN, Bhan AK, Shaw SY, Schreiber SL, Virgin HW, Shamji AF, Stappenbeck TS, Reinecker HC, Xavier RJ. Atg16l1 is Required for Autophagy in Intestinal Epithelial Cells and Protection of Mice From Salmonella Infection. Gastroenterology. 2013. PMID: 23973919.
  23. Graham DB, Xavier RJ. From genetics of inflammatory bowel disease towards mechanistic insights. Trends Immunol. 2013;34(8):371-8. PMID: 23639549.
  24. Ananthakrishnan AN, Xavier RJ. How does genotype influence disease phenotype in inflammatory bowel disease? Inflamm Bowel Dis. 2013;19(9):2021-30. PMID: 23644824.
  25. Tannahill GM, Curtis AM, Adamik J, Palsson-McDermott EM, McGettrick AF, Goel G, Frezza C, Bernard NJ, Kelly B, Foley NH, Zheng L, Gardet A, Tong Z, Jany SS, Corr SC, Haneklaus M, Caffrey BE, Pierce K, Walmsley S, Beasley FC, Cummins E, Nizet V, Whyte M, Taylor CT, Lin H, Masters SL, Gottlieb E, Kelly VP, Clish C, Auron PE, Xavier RJ, O'Neill LA. Succinate is an inflammatory signal that induces IL-1beta through HIF-1alpha. Nature. 2013;496(7444):238-42. PMID: 23535595.
  26. Conway KL, Kuballa P, Khor B, Zhang M, Shi HN, Virgin HW, Xavier RJ. ATG5 regulates plasma cell differentiation. Autophagy. 2013;9(4):528-37. PMID: 23327930.
  27. Smeekens SP, Ng A, Kumar V, Johnson MD, Plantinga TS, van Diemen C, Arts P, Verwiel ET, Gresnigt MS, Fransen K, van Sommeren S, Oosting M, Cheng SC, Joosten LA, Hoischen A, Kullberg BJ, Scott WK, Perfect JR, van der Meer JW, Wijmenga C, Netea MG, Xavier RJ. Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans. Nat Commun. 2013;4:1342. PMID: 23299892.
  28. Cho JL, Roche MI, Sandall B, Brass AL, Seed B, Xavier RJ, Medoff BD. Enhanced Tim3 activity improves survival after influenza infection. J Immunol. 2012;189(6):2879-89. PMID: 22875804.
  29. Kleinnijenhuis J, Quintin J, Preijers F, Joosten LA, Ifrim DC, Saeed S, Jacobs C, van Loenhout J, de Jong D, Stunnenberg HG, Xavier RJ, van der Meer JW, van Crevel R, Netea MG. Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci U S A. 2012;109(43):17537-42. PMID: 22988082.
  30. 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.
  31. Gardet A, Xavier RJ. Common alleles that influence autophagy and the risk for inflammatory bowel disease. Curr Opin Immunol. 2012;24(5):522-9. PMID: 23041451.
  32. Liu X, Nielsen GP, Rosenberg AE, Waterman PR, Yang W, Choy E, Sassi S, Yang S, Harmon DC, Yang C, Schwab JH, Kobayashi E, Mankin HJ, Xavier R, Weissleder R, Duan Z, Hornicek FJ. Establishment and characterization of a novel chordoma cell line: CH22. J Orthop Res. 2012;30(10):1666-73. PMID: 22504929.
  33. Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, Lee JC, Schumm LP, Sharma Y, 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, Satsangi J, Schreiber S, Simms LA, Sventoraityte J, Targan SR, Taylor KD, Tremelling M, Verspaget HW, De Vos M, Wijmenga C, Wilson DC, Winkelmann J, Xavier RJ, Zeissig S, Zhang B, Zhang CK, Zhao H, International IBDGC, 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(7422):119-24. PMID: 23128233.
  34. Duerr EM, Mizukami Y, Moriichi K, Gala M, Jo WS, Kikuchi H, Xavier RJ, Chung DC. Oncogenic KRAS regulates BMP4 expression in colon cancer cell lines. Am J Physiol Gastrointest Liver Physiol. 2012;302(10):G1223-30. PMID: 22383492.
  35. Wei SC, Rosenberg IM, Cao Z, Huett AS, Xavier RJ, Podolsky DK. Tribbles 2 (Trib2) is a novel regulator of toll-like receptor 5 signaling. Inflamm Bowel Dis. 2012;18(5):877-88. PMID: 22271508.
  36. Labbe C, Boucher G, Foisy S, Alikashani A, Nkwimi H, David G, Beaudoin M, Goyette P, Charron G, Xavier RJ, Rioux JD. Genome-wide expression profiling implicates a MAST3-regulated gene set in colonic mucosal inflammation of ulcerative colitis patients. Inflamm Bowel Dis. 2012;18(6):1072-80. PMID: 21994190.
  37. Xavier RJ, Gala MK, Bronzo BK, Kelly PJ. Case records of the Massachusetts General Hospital. Case 23-2012. A 59-year-old man with abdominal pain and weight loss. N Engl J Med. 2012;367(4):363-73. PMID: 22830467.
  38. Gewurz BE, Towfic F, Mar JC, Shinners NP, Takasaki K, Zhao B, Cahir-McFarland ED, Quackenbush J, Xavier RJ, Kieff E. Genome-wide siRNA screen for mediators of NF-kappaB activation. Proc Natl Acad Sci U S A. 2012;109(7):2467-72. PMID: 22308454.
  39. Lee J, Kim HR, Quinley C, Kim J, Gonzalez-Navajas J, Xavier R, Raz E. Autophagy suppresses interleukin-1beta (IL-1beta) signaling by activation of p62 degradation via lysosomal and proteasomal pathways. J Biol Chem. 2012;287(6):4033-40. PMID: 22167182.
  40. 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.
  41. Maloney NS, Thackray LB, Goel G, Hwang S, Duan E, Vachharajani P, Xavier R, Virgin HW. Essential cell-autonomous role for interferon (IFN) regulatory factor 1 in IFN-gamma-mediated inhibition of norovirus replication in macrophages. J Virol. 2012;86(23):12655-64. PMID: 22973039.
  42. Quintin J, Saeed S, Martens JH, Giamarellos-Bourboulis EJ, Ifrim DC, Logie C, Jacobs L, Jansen T, Kullberg BJ, Wijmenga C, Joosten LA, Xavier RJ, van der Meer JW, Stunnenberg HG, Netea MG. Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. Cell Host Microbe. 2012;12(2):223-32. PMID: 22901542.
  43. Su CW, Cao Y, Zhang M, Kaplan J, Su L, Fu Y, Walker WA, Xavier R, Cherayil BJ, Shi HN. Helminth infection impairs autophagy-mediated killing of bacterial enteropathogens by macrophages. J Immunol. 2012;189(3):1459-66. PMID: 22732589.
  44. Hwang S, Maloney NS, Bruinsma MW, Goel G, Duan E, Zhang L, Shrestha B, Diamond MS, Dani A, Sosnovtsev SV, Green KY, Lopez-Otin C, Xavier RJ, Thackray LB, Virgin HW. Nondegradative role of Atg5-Atg12/ Atg16L1 autophagy protein complex in antiviral activity of interferon gamma. Cell Host Microbe. 2012;11(4):397-409. PMID: 22520467.
  45. Etzrodt M, Cortez-Retamozo V, Newton A, Zhao J, Ng A, Wildgruber M, Romero P, Wurdinger T, Xavier R, Geissmann F, Meylan E, Nahrendorf M, Swirski FK, Baltimore D, Weissleder R, Pittet MJ. Regulation of monocyte functional heterogeneity by miR-146a and Relb. Cell Rep. 2012;1(4):317-24. PMID: 22545247.
  46. Zhao Y, Alonso C, Ballester I, Song JH, Chang SY, Guleng B, Arihiro S, Murray PJ, Xavier R, Kobayashi KS, Reinecker HC. Control of NOD2 and Rip2-dependent innate immune activation by GEF-H1. Inflamm Bowel Dis. 2012;18(4):603-12. PMID: 21887730.
  47. Klionsky DJ, et al. Autophagy. 2012;8(4):445-544. PMID: 22966490.
  48. Papa E, Docktor M, Smillie C, Weber S, Preheim SP, Gevers D, Giannoukos G, Ciulla D, Tabbaa D, Ingram J, Schauer DB, Ward DV, Korzenik JR, Xavier RJ, Bousvaros A, Alm EJ. Non-invasive mapping of the gastrointestinal microbiota identifies children with inflammatory bowel disease. PLoS One. 2012;7(6):e39242. PMID: 22768065.
  49. Kuballa P, Nolte WM, Castoreno AB, Xavier RJ. Autophagy and the immune system. Annu Rev Immunol. 2012;30:611-46. PMID: 22449030.
  50. Morgan XC, Tickle TL, Sokol H, Gevers D, Devaney KL, Ward DV, Reyes JA, Shah SA, LeLeiko N, Snapper SB, Bousvaros A, Korzenik J, Sands BE, Xavier RJ, Huttenhower C. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol. 2012;13(9):R79. PMID: 23013615.
  51. Russo BC, Horzempa J, O'Dee DM, Schmitt DM, Brown MJ, Carlson PE, Jr., Xavier RJ, Nau GJ. A Francisella tularensis locus required for spermine responsiveness is necessary for virulence. Infect Immun. 2011;79(9):3665-76. PMID: 21670171.
  52. Ng A, Xavier RJ. Leucine-rich repeat (LRR) proteins: integrators of pattern recognition and signaling in immunity. Autophagy. 2011;7(9):1082-4. PMID: 21606681.
  53. 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, National Institute of D, Digestive Kidney Diseases Inflammatory Bowel Disease Genetics C, United Kingdom Inflammatory Bowel Disease Genetics C, International Inflammatory Bowel Disease Genetics C, 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.
  54. Ng AC, Eisenberg JM, Heath RJ, Huett A, Robinson CM, Nau GJ, Xavier RJ. Human leucine-rich repeat proteins: a genome-wide bioinformatic categorization and functional analysis in innate immunity. Proc Natl Acad Sci U S A. 2011;108 Suppl 1:4631-8. PMID: 20616063.
  55. Anderson CA, Boucher G, Lees CW, Franke A, D'Amato M, Taylor KD, Lee JC, Goyette P, Imielinski M, Latiano A, Lagace C, Scott R, Amininejad L, Bumpstead S, Baidoo L, Baldassano RN, Barclay M, Bayless TM, Brand S, Buning C, Colombel JF, Denson LA, De Vos M, Dubinsky M, Edwards C, Ellinghaus D, Fehrmann RS, Floyd JA, Florin T, Franchimont D, Franke L, Georges M, Glas J, Glazer NL, Guthery SL, Haritunians T, Hayward NK, Hugot JP, Jobin G, Laukens D, Lawrance I, Lemann M, Levine A, Libioulle C, Louis E, McGovern DP, Milla M, Montgomery GW, Morley KI, Mowat C, Ng A, Newman W, Ophoff RA, Papi L, Palmieri O, Peyrin-Biroulet L, Panes J, Phillips A, Prescott NJ, Proctor DD, Roberts R, Russell R, Rutgeerts P, Sanderson J, Sans M, Schumm P, Seibold F, Sharma Y, Simms LA, Seielstad M, Steinhart AH, Targan SR, van den Berg LH, Vatn M, Verspaget H, Walters T, Wijmenga C, Wilson DC, Westra HJ, Xavier RJ, Zhao ZZ, Ponsioen CY, Andersen V, Torkvist L, Gazouli M, Anagnou NP, Karlsen TH, Kupcinskas L, Sventoraityte J, Mansfield JC, Kugathasan S, Silverberg MS, Halfvarson J, Rotter JI, Mathew CG, Griffiths AM, Gearry R, Ahmad T, Brant SR, Chamaillard M, Satsangi J, Cho JH, Schreiber S, Daly MJ, Barrett JC, Parkes M, Annese V, Hakonarson H, Radford-Smith G, Duerr RH, Vermeire S, Weersma RK, Rioux JD. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat Genet. 2011;43(3):246-52. PMID: 21297633.
  56. Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature. 2011;474(7351):307-17. PMID: 21677747.
  57. Hirota SA, Ng J, Lueng A, Khajah M, Parhar K, Li Y, Lam V, Potentier MS, Ng K, Bawa M, McCafferty DM, Rioux KP, Ghosh S, Xavier RJ, Colgan SP, Tschopp J, Muruve D, MacDonald JA, Beck PL. NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis. Inflamm Bowel Dis. 2011;17(6):1359-72. PMID: 20872834.
  58. Wang S, Villablanca EJ, De Calisto J, Gomes DC, Nguyen DD, Mizoguchi E, Kagan JC, Reinecker HC, Hacohen N, Nagler C, Xavier RJ, Rossi-Bergmann B, Chen YB, Blomhoff R, Snapper SB, Mora JR. MyD88-dependent TLR1/2 signals educate dendritic cells with gut-specific imprinting properties. J Immunol. 2011;187(1):141-50. PMID: 21646294.
  59. Ramadas RA, Roche MI, Moon JJ, Ludwig T, Xavier RJ, Medoff BD. CARMA1 is necessary for optimal T cell responses in a murine model of allergic asthma. J Immunol. 2011;187(12):6197-207. PMID: 22075698.
  60. Orvedahl A, Sumpter R, Jr., Xiao G, Ng A, Zou Z, Tang Y, Narimatsu M, Gilpin C, Sun Q, Roth M, Forst CV, Wrana JL, Zhang YE, Luby-Phelps K, Xavier RJ, Xie Y, Levine B. Image-based genome-wide siRNA screen identifies selective autophagy factors. Nature. 2011;480(7375):113-7. PMID: 22020285.
  61. O'Donnell MA, Perez-Jimenez E, Oberst A, Ng A, Massoumi R, Xavier R, Green DR, Ting AT. Caspase 8 inhibits programmed necrosis by processing CYLD. Nat Cell Biol. 2011;13(12):1437-42. PMID: 22037414.
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  91. Medoff BD, Landry AL, Wittbold KA, Sandall BP, Derby MC, Cao Z, Adams JC, Xavier RJ. CARMA3 mediates lysophosphatidic acid-stimulated cytokine secretion by bronchial epithelial cells. Am J Respir Cell Mol Biol. 2009;40(3):286-94. PMID: 18757306.
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  99. Brass AL, Huang IC, Benita Y, John SP, Krishnan MN, Feeley EM, Ryan BJ, Weyer JL, van der Weyden L, Fikrig E, Adams DJ, Xavier RJ, Farzan M, Elledge SJ. The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell. 2009;139(7):1243-54. PMID: 20064371.
  100. Imielinski M, Baldassano RN, Griffiths A, Russell RK, Annese V, Dubinsky M, Kugathasan S, Bradfield JP, Walters TD, Sleiman P, Kim CE, Muise A, Wang K, Glessner JT, Saeed S, Zhang H, Frackelton EC, Hou C, Flory JH, Otieno G, Chiavacci RM, Grundmeier R, Castro M, Latiano A, Dallapiccola B, Stempak J, Abrams DJ, Taylor K, McGovern D, Western Regional Alliance for Pediatric IBD, Silber G, Wrobel I, Quiros A, International IBDGC, Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD, Brant SR, Silverberg MS, Taylor KD, Barmuda MM, Bitton A, Dassopoulos T, Datta LW, Green T, Griffiths AM, Kistner EO, Murtha MT, Regueiro MD, Rotter JI, Schumm LP, Steinhart AH, Targan SR, Xavier RJ, Consortium NIG, Libioulle C, Sandor C, Lathrop M, Belaiche J, Dewit O, Gut I, Heath S, Laukens D, Mni M, Rutgeerts P, Van Gossum A, Zelenika D, Franchimont D, Hugot JP, de Vos M, Vermeire S, Louis E, Belgian-French IBDC, Wellcome Trust Case Control C, Cardon LR, Anderson CA, Drummond H, Nimmo E, Ahmad T, Prescott NJ, Onnie CM, Fisher SA, Marchini J, Ghori J, Bumpstead S, Gwillam R, Tremelling M, Delukas P, Mansfield J, Jewell D, Satsangi J, Mathew CG, Parkes M, Georges M, Daly MJ, Heyman MB, Ferry GD, Kirschner B, Lee J, Essers J, Grand R, Stephens M, Levine A, Piccoli D, Van Limbergen J, Cucchiara S, Monos DS, Guthery SL, Denson L, Wilson DC, Grant SF, Daly M, Silverberg MS, Satsangi J, Hakonarson H. Common variants at five new loci associated with early-onset inflammatory bowel disease. Nat Genet. 2009;41(12):1335-40. PMID: 19915574.
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  105. Krishnan MN, Ng A, Sukumaran B, Gilfoy FD, Uchil PD, Sultana H, Brass AL, Adametz R, Tsui M, Qian F, Montgomery RR, Lev S, Mason PW, Koski RA, Elledge SJ, Xavier RJ, Agaisse H, Fikrig E. RNA interference screen for human genes associated with West Nile virus infection. Nature. 2008;455(7210):242-5. PMID: 18690214.
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  145. Mahoney ZX, Sammut B, Xavier RJ, Cunningham J, Go G, Brim KL, Stappenbeck TS, Miner JH, Swat W. Discs-large homolog 1 regulates smooth muscle orientation in the mouse ureter. Proc Natl Acad Sci U S A. 2006;103(52):19872-7. PMID: 17172448.
  146. Liu SM, Xavier R, Good KL, Chtanova T, Newton R, Sisavanh M, Zimmer S, Deng C, Silva DG, Frost MJ, Tangye SG, Rolph MS, Mackay CR. Immune cell transcriptome datasets reveal novel leukocyte subset-specific genes and genes associated with allergic processes. J Allergy Clin Immunol. 2006;118(2):496-503. PMID: 16890777.
  147. Giallourakis C, Cao Z, Green T, Wachtel H, Xie X, Lopez-Illasaca M, Daly M, Rioux J, Xavier R. A molecular-properties-based approach to understanding PDZ domain proteins and PDZ ligands. Genome Res. 2006;16(8):1056-72. PMID: 16825666.
  148. Landry A, Xavier R. Isolation and analysis of lipid rafts in cell-cell interactions. Methods Mol Biol. 2006;341:251-82. PMID: 16799204.
  149. Barnich N, Hisamatsu T, Aguirre JE, Xavier R, Reinecker HC, Podolsky DK. GRIM-19 interacts with nucleotide oligomerization domain 2 and serves as downstream effector of anti-bacterial function in intestinal epithelial cells. J Biol Chem. 2005;280(19):19021-6. PMID: 15753091.
  150. Xavier R, Seed B. PDZ domains and the politics of polarity in lymphocytes. Immunity. 2005;22(6):655-6. PMID: 15963778.
  151. Barnich N, Aguirre JE, Reinecker HC, Xavier R, Podolsky DK. Membrane recruitment of NOD2 in intestinal epithelial cells is essential for nuclear factor-{kappa}B activation in muramyl dipeptide recognition. J Cell Biol. 2005;170(1):21-6. PMID: 15998797.
  152. Lopez-Ilasaca MA, Bernabe-Ortiz JC, Na SY, Dzau VJ, Xavier RJ. Bioluminescence resonance energy transfer identify scaffold protein CNK1 interactions in intact cells. FEBS Lett. 2005;579(3):648-54. PMID: 15670823.
  153. Xavier R, Podolsky DK. Commensal flora: wolf in sheep's clothing. Gastroenterology. 2005;128(4):1122-6. PMID: 15825094.
  154. Ting A, Lichtenthaler S, Xavier R, Na SY, Rabizadeh S, Holmes T, Seed B. Large-scale screens for cDNAs with in vivo activity. Novartis Found Symp. 2005;267:219-29; discussion 229-30. PMID: 15999809.
  155. Ishiguro K, Xavier R. Homer-3 regulates activation of serum response element in T cells via its EVH1 domain. Blood. 2004;103(6):2248-56. PMID: 14645007.
  156. Beck PL, Wong JF, Li Y, Swaminathan S, Xavier RJ, Devaney KL, Podolsky DK. Chemotherapy- and radiotherapy-induced intestinal damage is regulated by intestinal trefoil factor. Gastroenterology. 2004;126(3):796-808. PMID: 14988834.
  157. Xavier R, Rabizadeh S, Ishiguro K, Andre N, Ortiz JB, Wachtel H, Morris DG, Lopez-Ilasaca M, Shaw AC, Swat W, Seed B. Discs large (Dlg1) complexes in lymphocyte activation. J Cell Biol. 2004;166(2):173-8. PMID: 15263016.
  158. Rabizadeh S, Xavier RJ, Ishiguro K, Bernabeortiz J, Lopez-Ilasaca M, Khokhlatchev A, Mollahan P, Pfeifer GP, Avruch J, Seed B. The scaffold protein CNK1 interacts with the tumor suppressor RASSF1A and augments RASSF1A-induced cell death. J Biol Chem. 2004;279(28):29247-54. PMID: 15075335.
  159. Beck PL, Xavier R, Wong J, Ezedi I, Mashimo H, Mizoguchi A, Mizoguchi E, Bhan AK, Podolsky DK. Paradoxical roles of different nitric oxide synthase isoforms in colonic injury. Am J Physiol Gastrointest Liver Physiol. 2004;286(1):G137-47. PMID: 14665440.
  160. Ishiguro K, Cao Z, Ilasca ML, Ando T, Xavier R. Wave2 activates serum response element via its VCA region and functions downstream of Rac. Exp Cell Res. 2004;301(2):331-7. PMID: 15530867.
  161. Mizoguchi E, Xavier RJ, Reinecker HC, Uchino H, Bhan AK, Podolsky DK, Mizoguchi A. Colonic epithelial functional phenotype varies with type and phase of experimental colitis. Gastroenterology. 2003;125(1):148-61. PMID: 12851880.
  162. Swat W, Xavier R, Mizoguchi A, Mizoguchi E, Fredericks J, Fujikawa K, Bhan AK, Alt FW. Essential role for Vav1 in activation, but not development, of gammadelta T cells. Int Immunol. 2003;15(2):215-21. PMID: 12578851.
  163. Beck PL, Rosenberg IM, Xavier RJ, Koh T, Wong JF, Podolsky DK. Transforming growth factor-beta mediates intestinal healing and susceptibility to injury in vitro and in vivo through epithelial cells. Am J Pathol. 2003;162(2):597-608. PMID: 12547717.
  164. Schiffmann R, Mankin H, Dambrosia JM, Xavier RJ, Kreps C, Hill SC, Barton NW, Rosenthal DI. Decreased bone density in splenectomized Gaucher patients receiving enzyme replacement therapy. Blood Cells Mol Dis. 2002;28(2):288-96. PMID: 12064924.
  165. Mizoguchi E, Mizoguchi A, Takedatsu H, Cario E, de Jong YP, Ooi CJ, Xavier RJ, Terhorst C, Podolsky DK, Bhan AK. Role of tumor necrosis factor receptor 2 (TNFR2) in colonic epithelial hyperplasia and chronic intestinal inflammation in mice. Gastroenterology. 2002;122(1):134-44. PMID: 11781288.
  166. Khokhlatchev A, Rabizadeh S, Xavier R, Nedwidek M, Chen T, Zhang XF, Seed B, Avruch J. Identification of a novel Ras-regulated proapoptotic pathway. Curr Biol. 2002;12(4):253-65. PMID: 11864565.
  167. Colucci R, Fleming JV, Xavier R, Wang TC. L-histidine decarboxylase decreases its own transcription through downregulation of ERK activity. Am J Physiol Gastrointest Liver Physiol. 2001;281(4):G1081-91. PMID: 11557529.
  168. Mankin HJ, Rosenthal DI, Xavier R. Gaucher disease. New approaches to an ancient disease. J Bone Joint Surg Am. 2001;83-A(5):748-62. PMID: 11379747.
  169. Merscher S, Funke B, Epstein JA, Heyer J, Puech A, Lu MM, Xavier RJ, Demay MB, Russell RG, Factor S, Tokooya K, Jore BS, Lopez M, Pandita RK, Lia M, Carrion D, Xu H, Schorle H, Kobler JB, Scambler P, Wynshaw-Boris A, Skoultchi AI, Morrow BE, Kucherlapati R. TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome. Cell. 2001;104(4):619-29. PMID: 11239417.
  170. Chung RT, He W, Saquib A, Contreras AM, Xavier RJ, Chawla A, Wang TC, Schmidt EV. Hepatitis C virus replication is directly inhibited by IFN-alpha in a full-length binary expression system. Proc Natl Acad Sci U S A. 2001;98(17):9847-52. PMID: 11493707.
  171. Chawla N, Andre N, Choi M, Bernabe-Ortiz JC, Xavier R. An update on lymphocyte activation and signal transduction in inflammation. VI International Symposium on Inflammatory Bowel Diseases. 2001:11-30.
  172. Xavier RJ, Podolsky DK. Microbiology. How to get along--friendly microbes in a hostile world. Science. 2000;289(5484):1483-4. PMID: 10991734.
  173. Beck PL, Xavier R, Lu N, Nanda NN, Dinauer M, Podolsky DK, Seed B. Mechanisms of NSAID-induced gastrointestinal injury defined using mutant mice. Gastroenterology. 2000;119(3):699-705. PMID: 10982764.
  174. Muehlhoefer A, Saubermann LJ, Gu X, Luedtke-Heckenkamp K, Xavier R, Blumberg RS, Podolsky DK, MacDermott RP, Reinecker HC. Fractalkine is an epithelial and endothelial cell-derived chemoattractant for intraepithelial lymphocytes in the small intestinal mucosa. J Immunol. 2000;164(6):3368-76. PMID: 10706732.
  175. Xavier R, Seed B. Membrane compartmentation and the response to antigen. Curr Opin Immunol. 1999;11(3):265-9. PMID: 10375560.
  176. Itoh H, Beck PL, Inoue N, Xavier R, Podolsky DK. A paradoxical reduction in susceptibility to colonic injury upon targeted transgenic ablation of goblet cells. J Clin Invest. 1999;104(11):1539-47. PMID: 10587517.
  177. Fukumura D, Xavier R, Sugiura T, Chen Y, Park EC, Lu N, Selig M, Nielsen G, Taksir T, Jain RK, Seed B. Tumor induction of VEGF promoter activity in stromal cells. Cell. 1998;94(6):715-25. PMID: 9753319.
  178. Lown B, Bukachi F, Xavier R. Health information in the developing world. Lancet. 1998;352 Suppl 2:SII34-8. PMID: 9798645.
  179. Swat W, Fujikawa K, Ganiatsas S, Yang D, Xavier RJ, Harris NL, Davidson L, Ferrini R, Davis RJ, Labow MA, Flavell RA, Zon LI, Alt FW. SEK1/MKK4 is required for maintenance of a normal peripheral lymphoid compartment but not for lymphocyte development. Immunity. 1998;8(5):625-34. PMID: 9620683.
  180. Xavier R, Brennan T, Li Q, McCormack C, Seed B. Membrane compartmentation is required for efficient T cell activation. Immunity. 1998;8(6):723-32. PMID: 9655486.
  181. Liang TJ, Reid AE, Xavier R, Cardiff RD, Wang TC. Transgenic expression of tpr-met oncogene leads to development of mammary hyperplasia and tumors. J Clin Invest. 1996;97(12):2872-7. PMID: 8675700.
  182. Amstalden EM, Xavier R, Kattapuram SV, Bertolo MB, Swartz MN, Rosenberg AE. Paracoccidioidomycosis of bones and joints. A clinical, radiologic, and pathologic study of 9 cases. Medicine (Baltimore). 1996;75(4):213-25. PMID: 8699961.
  183. Greenberg S, Chang P, Wang DC, Xavier R, Seed B. Clustered syk tyrosine kinase domains trigger phagocytosis. Proc Natl Acad Sci U S A. 1996;93(3):1103-7. PMID: 8577722.
  184. Xavier R, Podolsky DK. Addressing lymphocytes for mucosal delivery in ibd. Inflamm Bowel Dis. 1995;1(4):343-4. PMID: 23282439.
  185. Rosenthal DI, Doppelt SH, Mankin HJ, Dambrosia JM, Xavier RJ, McKusick KA, Rosen BR, Baker J, Niklason LT, Hill SC, et al. Enzyme replacement therapy for Gaucher disease: skeletal responses to macrophage-targeted glucocerebrosidase. Pediatrics. 1995;96(4 Pt 1):629-37. PMID: 7567322.
  186. Thadhani RI, Camargo CA, Jr., Xavier RJ, Fang LS, Bazari H. Atheroembolic renal failure after invasive procedures. Natural history based on 52 histologically proven cases. Medicine (Baltimore). 1995;74(6):350-8. PMID: 7500898.
  187. Pins MR, Mankin HJ, Xavier RJ, Rosenthal DI, Dickersin GR, Rosenberg AE. Malignant epithelioid hemangioendothelioma of the tibia associated with a bone infarct in a patient who had Gaucher disease. A case report. J Bone Joint Surg Am. 1995;77(5):777-81. PMID: 7744904.
  188. Mullaney J, Xavier R. SatelLife: Building an Electronic Health Network in the Developing World. Studies in Health Technology and Informatics. 1995;23:265-276.
  189. Seed B, Kolanus W, Romeo C, Xavier R. Nonreceptor tyrosine kinases in aggregation-mediated cell activation. Adv Exp Med Biol. 1994;365:111-9. PMID: 7887297.
  190. Rachmilewitz D, Stamler JS, Karmeli F, Loscalzo J, Xavier RJ, Podolsky DK. Role of nitric oxide in the pathogenesis of IBD. Inflammatory Bowel Diseases 1994. 1994:82-90.
  191. Rachmilewitz D, Stamler JS, Karmeli F, Mullins ME, Singel DJ, Loscalzo J, Xavier RJ, Podolsky DK. Peroxynitrite-induced rat colitis--a new model of colonic inflammation. Gastroenterology. 1993;105(6):1681-8. PMID: 8253344.
  192. Xavier RJ, Stein CM, Kiire CF, Arrow J, Kitai I. Value of the history and stool occult blood test in selection of patients for upper endoscopy in Zimbabwe. East Afr Med J. 1992;69(5):268-71. PMID: 1644046.
  193. Xavier RJ, Mann J, Tarantola DJ, Netter TW. AIDS and tuberculosis: A dangerous synergy. AIDS in the World. 1992:148-163.
  194. Bigger RJ, Xavier RJ. AIDS and Cancer. AIDS in the World. 1992:134-143.