Massachusetts General Hospital

The discovery of important molecular sensors, mediators, and effectors involved in innate immunity and autophagy requires a deeper exploration of how these function as integrated systems.  Our lab utilizes 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-pathogen-microbiome interactions, inflammation, autophagy and pathogenesis of complex immunological diseases including Crohn’s disease, ulcerative colitis and Type I diabetes. We are particularly interested in pursuing a systems-level understanding of microbial sensing mechanisms and regulatory control in immune signaling circuits through transcriptional, metabolic and epigenetic programming.

Aylwin Ng is an Instructor in Medicine at Harvard Medical School, Assistant in Immunology at Massachusetts General Hospital, Associate Investigator at the Center for the Study of Inflammatory Bowel Disease at MGH, and an associated researcher at the Broad Institute of MIT & Harvard. He holds a Master’s degree in computational biology from Imperial College London and a Ph.D./D.Phil. in molecular virology and immunology from Oxford University. He has trained in inter-disciplinary fields spanning functional genomics, computational and experimental biology, and completed fellowships in computational biology at the Ludwig Institute for Cancer Research (UK branch) and in integrative systems biology at the Center for Computational & Integrative Biology (CCIB) at MGH.

Contact information:
Dr. Aylwin Ng
Gastrointestinal Unit
Gray Jackson 8, Room GRJ-825A
Massachusetts General Hospital
55 Fruit Street, Boston, MA 02114
Office: 617-724-9384
E-mail:

Post-doctoral fellowship opportunities in Computational and Integrative Systems biology

Post-doctoral fellowship opportunities are available in the lab for creative, talented and highly motivated computational scientists who have a strong interest in pursuing computational and systems-level research into understanding biological circuits, and pathways in regulating immune responses to microbes or their dysregulation in complex genetic diseases, including Crohn’s disease, ulcerative colitis and Type I diabetes.

Applicants should have a Ph.D., with a background in one or more of the following:

• computational biology/bioinformatics,
• engineering,
• computer science,
• computational statistics,
• machine learning/data-mining, or
• signal processing

and proficiency in Java/C, Python/Perl, and MATLAB/R.

If you are interested in applying, please email your interests, curriculum vitae and reference letters to:

Selected Publications

1. 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
2. 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
3. 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
4. Ng A, Xavier RJ. Leucine-rich repeat (LRR) proteins: integrators of pattern recognition and signaling in immunity. Autophagy (2011) 7: 1082-4
5. 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
6. 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
7. 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
8. Ng AC. Integrative systems biology and networks in autophagy. Seminars in Immunopathology (2010) 32: 355-61
9. 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
10. 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
11. 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
12. 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
13. 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
14. 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
15. 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
16. 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
17. 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
18. 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
19. 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
20. 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
21. 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
22. 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
23. 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
24. 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.
25. 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
26. 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
27. 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
28. 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
29. 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