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Research

Patterns, Microbes, Sensors & Disease

We are interested in investigating pattern-recognition molecules, sensors monitoring cellular states, communication circuits and how these function as integrated systems in innate immunity, autophagy and disease. We utilize integrative systems approaches involving computation and high-throughput experimentation (RNA interference (RNAi) and chemical biology screens, transcriptomics, proteomics, metabolomics, and data from genome-wide association studies (GWAS)) to investigate the underlying signaling pathways and regulatory networks that define host-microbial interactions, inflammation, autophagy and pathogenesis of complex immunological diseases including Crohn’s disease and ulcerative colitis.

The lab is in the Division of Gastroenterology in the Department of Medicine and also in the Center for the Study of Inflammatory Bowel Disease (CSIBD) at Massachusetts General Hospital and Harvard Medical School.

MGH HMS



Publications

  1. Zhu J, Davoli T, Perriera JM, Chin CR, Gaiha GD, John SP, Sigiollot FD, Gao G, Xu Q, Qu H, Pertel T, Sims JS, Smith JA, Baker RE, Maranda L, Ng A, Elledge SJ, Brass AL. Comprehensive Identification of Host Modulators of HIV-1 Replication using Multiple Orthologous RNAi Reagents. Cell Reports (2014) 9: 752-66
  2. Saeed S, Quintin J, Kerstens HH, Rao NA, Aghajanirefah A, Matarese F, Cheng SC, Ratter J, Berentsen K, van der Ent MA, Sharifi N, Janssen-Megens EM, Ter Huurne M, Mandoli A, van Schaik T, Ng A, Burden F, Downes K, Frontini M, Kumar V, Giamarellos-Bourboulis EJ, Ouwehand WH, van der Meer JW, Joosten LA, Wijmenga C, Martens JH, Xavier RJ, Logie C, Netea MG, Stunnenberg HG. Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. Science (2014) 345: 1251086
  3. Cheng SC, Quintin J, Cramer RA, Shepardson KM, Saeed S, Kumar V, Giamarellos-Bourboulis EJ, Martens JH, Rao NA, Aghajanirefah A, Manjeri GR, Li Y, Ifrim DC, Arts RJ, van der Meer BM, Deen PM, Logie C, O'Neill LA, Willems P, van de Veerdonk FL, van der Meer JW, Ng A, Joosten LA, Wijmenga C, Stunnenberg HG, Xavier RJ, Netea MG. mTOR- and HIF-1a-mediated aerobic glycolysis as metabolic basis for trained immunity. Science (2014) 345: 1250684
  4. Buffen K, Oosting M, Quintin J, Ng A, Kleinnijenhuis J, Kumar V, van de Vosse E, Wijmenga C, van Crevel R, Oosterwijk E, Grotenhuis AJ, Vermeulen SH, Kiemeney LA, van de Veerdonk FL, Chamilos G, Xavier RJ, van der Meer JW, Netea MG, Joosten LA. Autophagy Controls BCG-Induced Trained Immunity and the Response to Intravesical BCG Therapy for Bladder Cancer. PLoS Pathogens (2014) 10: e1004485
  5. van der Sijde MR, Ng A*, Fu J*. Systems genetics: From GWAS to disease pathways. Biochimica et Biophysica Acta (2014) 1842: 1903-1909
  6. Lee E, Koo Y, Ng A, Wei Y, Luby-Phelps K, Juraszek A, Xavier RJ, Cleaver O, Levine B, Amatruda JF. Autophagy is essential for cardiac morphogenesis during vertebrate development. Autophagy (2014) 10: 572-87
  7. 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 SC, Joosten LAB, Hoischen A, Kullberg BJ, Scott WK, Perfect JR, van der Meer JWM, Wijmenga C, Netea MG, Xavier RJ. Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans. Nature Communications (2013) 4: 1342
  8. 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 Reports (2012) 1: 317-324
  9. 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. Proceedings of the National Academy of Sciences USA (2011) 108 Suppl 1: 4631-8
  10. Ng A, Xavier RJ. Leucine-rich repeat (LRR) proteins: integrators of pattern recognition and signaling in immunity. Autophagy (2011) 7: 1082-4
  11. 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: 113-7
  12. 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. Nature Cell Biology (2011) 13: 1437-42
  13. Anderson CA, Boucher G, Lees CW, Franke A, D'Amato M, Taylor KD, Lee JC, Goyette P, …, Ng A, …, 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. Nature Genetics (2011) 43: 246-52
  14. Ng AC. Integrative systems biology and networks in autophagy. Seminars in Immunopathology (2010) 32: 355-61
  15. Cadwell K, Patel KK, Maloney NS, Liu TC, Ng AC, Storer CE, Head RD, Xavier R, Stappenbeck TS, Virgin HW. Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine. Cell (2010) 141: 1135-45
  16. Yoon JC, Ng A, Kim BH, Bianco A, Xavier RJ, Elledge SJ. Wnt signaling regulates mitochondrial physiology and insulin sensitivity. Genes and Development (2010) 24: 1507-18
  17. Lipinski MM, Hoffman G*, Ng A*, Zhou W, Py BF, Hsu E, Liu X, Eisenberg J, Liu J, Blenis J, Xavier RJ, Yuan J. A genome-wide siRNA screen reveals multiple mTORC1 independent signaling pathways regulating autophagy under normal nutritional conditions. Developmental Cell (2010) 18: 1041-52
  18. Riley BE, Kaiser SE, Shaler TA, Ng AC, Hara T, Hipp MS, Lage K, Xavier RJ, Ryu KY, Taguchi K, Yamamoto M, Tanaka K, Mizushima N, Komatsu M, Kopito RR. Ubiquitin accumulation in autophagy-deficient mice is dependent on the Nrf2-mediated stress response pathway: a potential role for protein aggregation in autophagic substrate selection. Journal of Cell Biology (2010) 191: 537-52
  19. Lipinski MM, Zheng B, Lu T, Yan Z, Py BF, Ng A, Xavier RJ, Li C, Yankner BA, Scherzer CR, Yuan J. Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer's disease. Proceedings of the National Academy of Sciences USA (2010) 107: 14164-9
  20. Huett A*, Ng A*, Cao Z, Kuballa P, Komatsu M, Daly MJ, Podolsky DK, Xavier RJ. A novel hybrid yeast-human network analysis reveals an essential role for FNBP1L in antibacterial autophagy. Journal of Immunology (2009) 182: 4917-30
  21. Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, Schilter HC, Rolph MS, Mackay F, Artis D, Xavier RJ, Teixeira MM, Mackay CR. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature (2009) 461: 1282-6
  22. Li Q, Brass AL, Ng A, Hu Z, Xavier RJ, Liang TJ, Elledge SJ. A genome-wide genetic screen for host factors required for hepatitis C virus propagation. Proceedings of the National Academy of Sciences USA (2009) 106: 16410-5
  23. Stephenson LM, Miller BC, Ng A, Eisenberg J, Zhao Z, Cadwell K, Graham DB, Mizushima NN, Xavier R, Virgin HW, Swat W. Identification of Atg5-dependent transcriptional changes and increases in mitochondrial mass in Atg5-deficient T lymphocytes. Autophagy (2009) 5: 625-35
  24. Raychaudhuri S, Plenge RM, Rossin EJ, Ng AC, Purcell SM, Sklar P, Scolnick EM, Xavier RJ, Altshuler D, Daly MJ. Identifying relationships among genomic disease regions: predicting genes at pathogenic SNP associations and rare deletions. PLoS Genetics (2009) 5: e1000534
  25. 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: 242-5
  26. Irazoqui JE, Ng A, Xavier RJ, Ausubel FM. Role for beta-catenin and HOX transcription factors in Caenorhabditis elegans and mammalian host epithelial-pathogen interactions. Proceedings of the National Academy of Sciences USA (2008) 105: 17469-74
  27. Hitomi J, Christofferson DE*, Ng A*, Yao J, Degterev A, Xavier RJ, Yuan J. Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway. Cell (2008) 135: 1311-23
  28. Goyette P, Lefebvre C, Ng A, Brant SR, Cho JH, Duerr RH, Silverberg MS, Taylor KD, Latiano A, Aumais G, Deslandres C, Jobin G, Annese V, Daly MJ, Xavier RJ, Rioux JD. Gene-centric association mapping of chromosome 3p implicates MST1 in IBD pathogenesis. Mucosal Immunology (2008) 1: 131-8
  29. Fujiki K, Duerr EM, Kikuchi H, Ng A, Xavier RJ, Mizukami Y, Imamura T, Kulke MH, Chung DC. Hoxc6 is overexpressed in gastrointestinal carcinoids and interacts with JunD to regulate tumor growth. Gastroenterology (2008) 135: 907-16, 16 e1-2
  30. Friedman CS, O'Donnell MA, Legarda-Addison D, Ng A, Cardenas WB, Yount JS, Moran TM, Basler CF, Komuro A, Horvath CM, Xavier R, Ting AT. The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response. EMBO Reports (2008) 9: 930-624
  31. Duerr EM, Mizukami Y, Ng A, Xavier RJ, Kikuchi H, Deshpande V, Warshaw AL, Glickman J, Kulke MH, Chung DC. Defining molecular classifications and targets in gastroenteropancreatic neuroendocrine tumors through DNA microarray analysis. Endocrine Related Cancer (2008) 15: 243-56
  32. Ng A, Bursteinas B, Gao Q, Mollison E, Zvelebil M. pSTIING: a 'systems' approach towards integrating signalling pathways, interaction and transcriptional regulatory networks in inflammation and cancer. Nucleic Acids Research (2006) 34: D527-34
  33. Ng A, Bursteinas B, Gao Q, Mollison E, Zvelebil M. Resources for integrative systems biology: from data through databases to networks and dynamic system models. Briefings in Bioinformatics (2006) 7: 318-3027
  34. Ng A, Tang JP, Goh CH, Hui KM. Regulation of the H19 imprinting gene expression in human nasopharyngeal carcinoma by methylation. International Journal of Cancer (2003) 104: 179-87
  35. Ng A, Tscharke DC, Reading PC, Smith GL. The vaccinia virus A41L protein is a soluble 30 kDa glycoprotein that affects virus virulence. Journal of General Virology (2001) 82: 2095-105

 




People


Aylwin Ng
Principal Investigator,
Instructor in Medicine, Harvard Medical School,
Assistant in Immunology, Massachusetts General Hospital (MGH),
Associate Investigator, Center for the Study of Inflammatory Bowel Disease, MGH,
Associated Scientist, Broad Institute of MIT & Harvard.

Aylwin holds a D.Phil./Ph.D. from Oxford University and a Master of Science in Computational biology from Imperial College London. He conducts research in inter-disciplinary fields spanning functional genomics, computational and experimental biology, and completed fellowships in computational biology at the Ludwig Institute for Cancer Research (University College London) and in integrative systems biology at the Center for Computational & Integrative Biology (CCIB) at Massachusetts General Hospital & Harvard Medical School.



Ying Zhang
Post-doctoral Fellow, Harvard Medical School
Research Fellow, Massachusetts General Hospital
Visiting Post-doctoral Fellow, Broad Institute of MIT & Harvard.

Ying is from Vancouver, Canada. He is a Computational Biologist and has a Ph.D. from the University of British Columbia. His research interests include genome-wide transcriptome analysis and comparative genomics in host-pathogen interactions.



Opportunities

Applications Invited:


Post-doctoral position in Computational Biology


[Date Posted/Updated: Nov 20th, 2014]

We are currently recruiting a post-doctoral research fellow in Computational/Systems Biology.
We are seeking creative and highly motivated applicants who have a strong interest in pursuing computational and systems-level research to identify and understand biological circuits, regulatory networks and pathways underlying microbial sensing, host immune responses and processes implicated in complex human inflammatory disorders, including Crohn’s disease, ulcerative colitis and Celiac disease. This position also provides opportunities to participate in exciting multi-disciplinary research programs investigating the interplay of host genetics and environmental factors (including pathogens and gut microbiota) in influencing immune responses and disease outcomes.

Applicants should have a Ph.D., with a quantitative background in one or more of the following:
• computer science/machine learning/data-mining,
• computational biology, or
• computational statistics/physics/mathematics.

Programming proficiency in Java/C, Python/Perl, and MATLAB/R is required. Additionally, prior experience in Next-Generation sequencing (NGS)/RNA-seq analysis, and genome-wide epigenetic profiling, as evidenced by scientific publications in peer-reviewed journals, would be a plus. Excellent written and verbal communication skills are essential.

Interested applicants should email CV with contact information of three referees, and a cover letter outlining your research interests and career goals to: ang{at}ccib{dot}mgh{dot}harvard{dot}edu.



Contact Us

Gastrointestinal Unit, Massachusetts General Hospital & Harvard Medical School

Dr. Aylwin Ng
Massachusetts General Hospital
Gastrointestinal Unit, Jackson Building,
55 Fruit Street, Boston, MA 02114.

Phone (Office): 1-617-724-9384
E-mail: ang{at}ccib{dot}mgh{dot}harvard{dot}edu