Assoc Prof Tan Shyong Wei, Kevin

Appointment(s)

Associate Professor and Dean’s Chair
Head, Department of Microbiology and Immunology
Vice-Dean (Graduate Studies), Yong Loo Lin School of Medicine, NUS

Degree(s)

BSc (Hons), PhD, CBiol, FRSB

Biography

Kevin SW TAN is Associate Professor, Head, and Dean’s Chair of the Department of Microbiology and Immunology, National University of Singapore. He is also Vice-Dean, Graduate Studies, at the Yong Loo Lin School of Medicine. His curiosity for parasites originated from his graduate student days at NUS and blossomed during his postdoctoral stint at The Rockefeller University, New York City. He was awarded tenure in 2011, and now devotes more time to academic and administrative service, apart from his research. Kevin’s research focuses on understanding how parasites commit suicide and exploiting such knowledge to trigger death mechanisms as an anti-parasite strategy. He is also interested in the problem of drug resistance and his team has developed new ways to find drugs that overcome resistance. More recently, his team has embarked on projects focusing on the role of single cell eukaryotes (SCEs) in the host microbiome. He hopes that the research from his team will accelerate the finding of new cures for parasitic diseases.

Research Areas/Research Interest

The protistan parasites Plasmodium falciparum and Blastocystis
Malaria is a potentially fatal infectious disease caused by protozoan parasites of the genus Plasmodium. The most virulent species, Plasmodium falciparum, infects approximately 500 million people and claims 2 million lives annually. The parasite infects red blood cells (RBC) of all ages, multiplies within them, before rupturing the host cell to release parasite progeny. During intracellular development, the parasite modifies the infected RBC extensively, resulting in cells that are rigid and adherent, factors that contribute to malaria pathogenesis. Despite the importance of malaria, evidenced by overwhelming number of deaths, there are numerous gaps in our knowledge of P. falciparum biology. Furthermore, the cellular characteristics of the organism can be a hindrance to vaccine and drug development.
Our laboratory has developed numerous assays for the characterization of programmed cell death (PCD) pathways in the intestinal parasite Blastocystis and has applied this knowledge to cell death studies in P. falciparum. A malaria metacaspase homologue has been identified and cloned, and current studies are ongoing to characterize its role in malaria PCD. We, in collaboration with colleagues at Nanyang Technological University, are also adopting a microarray approach to identify key genes and proteins involved in activation of malaria PCD. Our laboratory is a member of the Global Enterprise for Micro-Mechanics and Molecular Medicine (GEM4), which leverages on international collaborations to study medically-important disease, including malaria. Using bioengineering approaches, we and our collaborators at Massachusetts Institute of Technology and Institute Pasteur have identified a new role for the parasite-encoded protein RESA, showing that it confers RBC membrane rigidity in infected cells. Current work includes the effects of drugs on infected cell biomechanical properties. Our laboratory, with researchers at the Department of Chemistry, is developing fluorescent-tagged drugs that can be used for live bioimaging of parasites to accelerate drug discovery and facilitate drug studies.
Our laboratory has contributed extensively to the current understanding of Blastocystis biology. Our research on this protozoan focuses on host-pathogen interactions, which aims to clarify its controversial role in intestinal disease. We have shown that the parasite exhibits IgA, IgM and IgG protease activity and induces contact-independent apoptosis, F-actin rearrangement, and barrier function disruption in IEC-6 cells. We have recently observed that parasite cysteine proteases mediate IL-8 production in human colonic epithelial T-84 cells in a NF-kB dependent manner.
Protozoan programmed cell death
We are also studying the phenomenon of programmed cell death (PCD) in protozoan parasites using Blastocystis and P. falciparum as model organisms. Our work on Blastocystis has shown that a variety of external stimuli can trigger PCD with features similar to those reported for mammalian cells, including links between caspase activation/ mitochondrial factors and DNA fragmentation. We are currently studying the molecules that are involved in the induction and regulation of PCD in P. falciparum and Blastocystis, with particular focus on caspase-dependent and independent pathways, including autophagic cell death. The identification of novel activators and targets of protozoan PCD provide exciting possibilities for anti-parasite strategies. In particular, we have observed that the P. falciparum digestive vacuole is a major mediator of drug-mediated PCD and preliminary studies indicated that it can be exploited as a novel drug target.

Selected Publications

Colonization with two different Blastocystis subtypes in DSS-induced colitis mice is associated with strikingly different microbiome and pathological features

Deng L, Wojciech L, Png CW, Kioh DYQ, Gu Y, Aung TT, Malleret B, Chan ECY, Peng G, Zhang YL, Gascoigne NRJ, Tan KSW

High-Content Phenotypic Screen of a Focused TCAMS Drug Library Identifies Novel Disruptors of the Malaria Parasite Calcium Dynamics

Chia W, Gomez-Lorenzo MG, Castellote I, Tong JX, Chandramohanadas R, Thu Chu TT, Shen W, Go ML, de Cozar C, Crespo B, Almela MJ, Neria-Serrano F, Franco V, Gamo FJ, Tan KSW

New insights into the interactions between Blastocystis, the gut microbiota, and host immunity

Deng L, Wojciech L, Gascoigne NRJ, Peng G, Tan KSW

Interactions between a pathogenic Blastocystis subtype and gut microbiota: in vitro and in vivo studies

Yason JA, Liang YR, Png CW, Zhang Y, Tan KSW

Successful Genetic Transfection of the Colonic Protistan Parasite Blastocystis for Reliable Expression of Ectopic Genes

Li FJ, Tsaousis AD, Purton P, Chow VTK, He CY, Tan KSW

Haem-activated promiscuous targeting of artemisinin in Plasmodium falciparum

Wang JG, Zhang CJ, Chia WN, Loh CCY, Li ZJ, Lee YM, He YK, Yuan LX, Lim TK, Liu M, Liew CX, Lee YQ, Zhang JB, Lu NC, Lim CT, Hua ZC, Liu B, Shen HM, Tan KSW,* Lin QS*