Yunn Hwen Gan

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 targeting multidrug resistant enteric bacteria.
• Multidrug resistance plasmid transmission in clinical Gram-negative bacteria.
• 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

Education

• Doctor of Philosophy (PhD) University of Wisconsin Madison (1991 — 1996)
• Bachelor of Science (BSc) Purdue University

Affiliations

• Associate Professor, Department of Biochemistry, Yong Loo Lin School of Medicine, NUS.
• Co-Director, Infectious Diseases Translational Research Program, Yong Loo Lin School of Medicine, NUS.
• Supervisor, NUS Graduate School for Integrative Sciences and Engineering (NGS), NUS.

Selected Publications

• Lim DRX, Chen Y, Ng LF, Gruber J, Gan YH. (2022). Glutathione catabolism by Enterobacteriaceae species to hydrogen sulfide adversely affects viability in host systems in the presence of 5’fluorodeoxyuridine. Mol Microbiol.
• Ku JWK and Gan YH. (2021). New roles for glutathione: Modulators of bacterial virulence and pathogenesis. Redox Biology 44, 102012.
• Molton JS, Lee R, Bertrand D, Ding Y, Kalimuddin S, Lye DC, Nagarajan N, Gan YH, Archuleta S. (2021). Stool metagenome analysis of patients with Klebisella pneumoniae liver abscess and their domestic partners. Int J Infect Dis 107, 1- 4.
• Zhong W, Shi Z, Mahadevegowda SH, Liu B, Zhang K, Koh CH, Ruan L, Chen Y, Zeden MS, Pee CJE, Marimuthu K, De PP, Ng OT, Zhu Y, Chi YR, Hammond PT, Yang L, Gan YH, Pethe K, Greenberg EP, Grundling A, and Chan-Park MB. (2020). Designer broad-spectrum polyimidazolium antibiotics. Proc Natl Acad Sci U S A 117, 31376-31385.
• Hoong BYD, Gan YH, Liu H, and Chen ES. (2020). cGAS-STING pathway in oncogenesis and cancer therapeutics. Oncotarget 11, 2930-2955.
• Ku JWK, Chen Y, Lim BJW, Gasser S, Crasta KC, and Gan YH. (2020). Bacterial-induced cell fusion is a danger signal triggering cGAS–STING pathway via micronuclei formation. Proceedings of the National Academy of Sciences.
• Chng KR, Ghosh TS, Tan YH, Nandi T, Lee IR, Ng AHQ, Li C, Ravikrishnan A, Lim KM, Lye D, et al. (2020). Metagenome-wide association analysis identifies microbial determinants of post-antibiotic ecological recovery in the gut. Nat Ecol Evol.
• Qi G, Hu F, Kenry, Chong KC, Wu M, Gan YH, and Liu B. (2020). Bacterium‐Templated Polymer for Self‐Selective Ablation of Multidrug‐Resistant Bacteria. Advanced Functional Materials.
• Chen Y, Marimuthu K, Teo J, Venkatachalam I, Cherng BPZ, De Wang L, Prakki SRS, Xu W, Tan YH, Nguyen LC, Koh TH, Ng OT and Gan YH. (2020). Acquisition of Plasmid with Carbapenem-Resistance Gene blaKPC2 in Hypervirulent Klebsiella pneumoniae, Singapore. Emerg Infect Dis 26, 549-559.
  
• Si Z, Lim HW, Tay MYF, Du Y, Ruan L, Qiu H, Zamudio-Vazquez R, Reghu S, Chen Y, Tiong WS, Marimuthu PPDe, Ng OT, Zhu Y, Gan YH, Chi YR, Duan H, Bazan GC, Greenberg EP, Chan-Park MB, and Pethe K. (2020). A Glycosylated Cationic Block Poly(beta-peptide) Reverses Intrinsic Antibiotic Resistance in All ESKAPE Gram-Negative Bacteria. Angew Chem Int Ed Engl 59, 6819-6826.
  
• Tan YH, Chen Y, Chu WHW, Sham LT, and Gan YH. (2020). Cell envelope defects of different capsule-null mutants in K1 hypervirulent Klebsiella pneumoniae can affect bacterial pathogenesis. Mol Microbiol.​
  
• Hoh CH, Tan YH, and Gan YH. (2019). Protective Role of Kupffer Cells and Macrophages in Klebsiella pneumoniae-Induced Liver Abscess Disease. Infect Immun 87.
  
• Ku JW, and Gan YH. (2019). Modulation of bacterial virulence and fitness by host glutathione. Curr Opin Microbiol 47, 8-13.
  
• 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.
  
• 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.
• 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.
• 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.
  
• 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).
• 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.
  
• 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.
  
• 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.
  
• 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.
  
• 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.
  
• 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.