A/P Yunn Hwen GAN

GAN Yunn Hwen

Associate Professor

+65 6516 3678
bchganyh@nus.edu.sg

Affiliations

Associate Professor, Department of Biochemistry, Yong Loo Lin School of Medicine, NUS.
Adjunct Research Associate Professor, Mechanobiology Institute
Supervisor, NUS Graduate School for Integrative Sciences and Engineering (NGS), NUS.

Biodata

Yunn-Hwen Gan graduated from Purdue University with a BSc (Honours) in Molecular Biology and University of Wisconsin-Madison with a PhD in medical microbiology and immunology. She is a world leading researcher in melioidosis, a disease primarily in the tropics caused by the bacterium Burkholderia pseudomallei. She established the first mucosal animal model in 2002 and had helped define the field by examining pathogen’s virulence as well as the host immune response to the disease. Her lab discovered a regulatory cascade that coordinately controlled two bacterial secretion systems which are absolutely critical for bacterial virulence. Other seminal findings include the discovery that the pathogen could infect plants and glutathione deficiency is the reason for increased disease risk to melioidosis for Type 2 diabetic patients. Her laboratory also works on identifying bacterial virulence factors of hypervirulent Klebsiella pneumoniae responsible for causing liver abscess, which is prominent in Asia. Meanwhile, studies are underway to define the gut and liver immune responses to the disease.

Research Interest

  • Novel strategies for targetting multidrug resistant enteric bacteria.
  • Type VI secretion systems in Burkholderia pseudomallei and Klebsiella pneumonaie.
  • Bacterial sensing of host environment by two component sensor/regulator systems.
  • Identifying risk factors for Klebsiella induced liver abscess.
  • The influence of microbiome on Klebsiella pneumoniae gut colonization

Selected Publications

  1. M C Lam M, Wyres KL, Duchêne S, Wick RR, Judd LM, Gan YH, Hoh CH, Archuleta S, Molton JS, Kalimuddin S, Koh TH, Passet V, Brisse S, Holt KE. (2018). Nat Commun. Population genomics of hypervirulent Klebsiella pneumoniae clonal-group 23 reveals early emergence and rapid global dissemination.2018 Jul 13;9(1):2703.

  2. Gamage MA, Liao C, Cheah IR, Chen Y, RX Lim D.R.X., Ku, JWK, Chee RSLC, Gengenbacher M, Seebeck FP, Halliwell B and Gan YH. (2018). The proteobacterial species Burkholderia pseudomallei produces ergothioneine which enhances virulence in mammalian infection. FASEB J. Jun 11:fj201800716. doi: 10.1096/fj.201800716.

  3. Lee IR, Sng E, Lee KO, Molton JS, Chan M, Kalimuddin S, Izharuddin E, Lye DC, Archuleta S, Gan YH. (2017). Comparison of diabetic and non-diabetic human leukocytic responses to different capsule types of Klebsiella pneumoniae responsible for causing pyogenic liver abscess. Front Cell Infect Microbiol. 2017 Sep 7;7:401. doi: 10.3389/fcimb.2017.00401.

  4. Gamage A, Lee KO, Gan YH. (2017). Anti-cancer drug HMBA acts as an adjuvant during intracellular bacterial infections by inducing Type I IFN through STING.J Immunol. 199(7):2491-2502.

  5. Tan YH, Gamage A, Gan YH. (2017). Complement-activated vitronectin enhances the invasion of non-phagocytic cells by bacterial pathogens Burkholderia and Klebsiella. Cell Microbiol. 2017 Aug;19(8). doi: 10.1111/cmi.12732

  6. Lee IR, Molton JS, Wyres KL, Gorrie C, Wong J, Hoh CH, Teo J, Kalimuddin S, Lye DC, Archuleta S, Holt KE and Gan YH(2016). Differential host susceptibility and bacterial virulence factors driving Klebsiella liver abscess in an ethnically diverse population. Sci Rep. 6:29316.

  7. Wong J, Chen Y and Gan YH. (2015). Host Cytosolic Glutathione Sensing by a Membrane Histidine Kinase Activates the Type VI Secretion System in an Intracellular Bacterium. Cell Host & Microbe. 18, 1-11.

  8. Lim YT, Jobichen C, Wong J, Limmathurotsakul D, Li S, Chen Y, Raida M, Srinivasan N, MacAry PA, Sivaraman J, Gan YH. (2015). Extended loop region of Hcp1 is critical for the assembly and function of type VI secretion system in Burkholderia pseudomallei. Sci Rep. Feb 4; 5:8235.

  9. Teh BE, French CT, Chen Y, Chen IG, Wu TH, Sagullo E, Chiou PY, Teitell MA, Miller JF, Gan YH. (2014). Type three secretion system-mediated escape of Burkholderia pseudomallei into the host cytosol is critical for the activation of NFκB. BMC Microbiol.May 6;14:115.

  10. Gamage AM, Lee KO, Gan YH. (2014). Effect of oral N-acetyl cysteine supplementation in Type 2 diabetic patients on intracellular glutathione content and innate immune responses to Burkholderia pseudomallei. Microbes Infect. 2014 Aug;16(8):661-71.

  11. Chen Y, Schröder I, French CT, Jaroszewicz A, Yee X, Teh BE, Toesca IJ, Miller JF, Gan YH. (2014). Characterization and analysis of the Burkholderia pseudomallei BsaN virulence regulon. BMC Microbiol. Aug 1;14(1):206.

  12. Ooi WF, Ong C, Nandi T, Kreisberg JF, Chua HH, Sun G, Chen Y, Mueller C, Conejero L, Eshaghi M, Ang RM, Liu J, Sobral BW, Korbsrisate S, Gan YH, Titball RW, Bancroft GJ, Valade E, Tan P. (2013) The Condition-Dependent Transcriptional Landscape of Burkholderia pseudomallei. PLOS Genetics. 9(9):e1003795.

  13. Lee SH, Wong RR, Chin CY, Lim TY, Eng SA, Kong C, Ijap NA, Lau MS, Lim MP, Gan YH, He FL, Tan MW, Nathan S. (2013). Burkholderia pseudomallei suppresses Caenorhabditis elegans immunity by specific degradation of a GATA transcription factor. PNAS. 110(37):15067-72.

  14. Gan YH. (2013). Host susceptibility factors to bacterial infections in Type 2 diabetes. PLOS Pathog. 2013 Dec;9(12):e1003794.

  15. Tan KS, Lee KO, Low KC, Gamage AM, Liu Y, Tan GY, Koh HQ, Alonso S and Gan YH. (2012). Glutathione deficiency in Type 2 diabetes impairs cytokine responses and control of intracellular bacteria. J. Clin. Invest. 122(6), 2289-2300.

  16. Chen Y, Wong J, Sun GW, Liu Y, Tan GY and Gan YH. (2011). Regulation of Type VI Secretion System during Burkholderia pseudomallei infection. Infect Immun 79(8), 3064-3073.

  17. Sun GW and Gan YH. (2010). Unraveling type III secretion systems in the highly versatile Burkholderia pseudomallei. Trends in Microbiol. 18(12), 561-568.

  18. Sun GW, Chen Y, Liu Y, Tan GY, Ong C, Tan P and Gan YH. (2010). Identification of a regulatory cascade controlling Type Three Secretion System 3 gene expression in Burkholderia pseudomallei. Mol. Microbiol. 76(3), 677-689.

  19. Tan KS, Chen Y, Lim YC, Tan GY, Liu Y, Lim YT, MacAry P and Gan YH. (2010). Suppression of host innate immune response by Burkholderia pseudomallei through the virulence factor TssM. J. Immunol. 184,5160-5171.

  20. Lee YH, Chen YH, Ouyang X and Gan YH. (2010). Identification of tomato plant as a novel host model for Burkholderia pseudomallei. BMC Microbiology. 10:28.

  21. Breitbach K, Sun GW, Ko¨hler J, Eske K, Wongprompitak P, Tan G, Liu Y, Gan YH and Ivo Steinmetz I. (2009). Caspase 1 mediates resistance in murine melioidosis. Infect. Immun. 77(4), 1589-1595.

  22. Ye Z, Lee CML, Sun GW and Gan YH. (2008) Burkholderia pseudomallei infection of T cells leads to T cell costimulation partially provided by flagellin. Infect. Immun. 76, 2541-2550.

  23. Hii CS, Sun GW, Goh JWK, Lu J, Stevens MP and Gan YH. (2008) IL-8 induction by Burkholderia pseudomallei can occur without Toll-like receptor signaling but requires a functional Type III secretion system. J. Infect. Dis., 197,1537-1547.

  24. Ye ZY and Gan YH. (2007). Flagellin contamination of recombinant heat shock protein 70 is responsible for its activity on T cells. J Biol Chem, 282:4479-4484.

  25. Koo GC and Gan YH. (2006). The innate interferon gamma response of BALB/c and C57BL/6 mice to in vitro Burkholderia pseudomallei infection. BMC Immunol, 7:19.

  26. Gan YH. (2005). Interaction of Burkholderia pseudomallei with host immune response: sleeping with the enemy? J. Infect. Dis., 192:1845-1850.

  27. Sun GW, Lu J, Pervaiz S, Cao WP and Gan YH. (2005). Caspase-1 dependent macrophage death induced by Burkholderia pseudomallei. Cell. Microbiol., 7(10), 1447-1458.

  28. Chen K, Sun GW, Chua KL, and Gan YH. (2005). Modified Virulence of Antibiotic-induced Burkholderia pseudomallei Filaments. Antimicrob. Agents Chemotherapy, 49(3), 1002-1009.

  29. Chua KL, Chan YY and Gan YH. (2003). Flagella, a virulence determinant in Burkholderia pseudomallei. Infect. Immun. 71, 1622-1629.

  30. Gan YH, Chua KL, Chua HH, Liu BP, Hii CS, Chong HL and Tan P (2002). Characterization of B. pseudomallei infection and identification of novel virulence factors using a C. elegans host system. Mol. Microbiol. 44, 1185-1197.

  31. Liu BP, Koo GC, Yap EH, Chua KL and Gan YH (2002). A model of differential susceptibility to mucosal infection of Burkholderia pseudomallei. Infect. Immun. 70, 504-511.