Chow Sek Chuen

Professor of Biomedical Sciences
School of Science

chow.sek.chuen@monash.edu
+603 5514 6096
Room 4-8-13
https://orcid.org/0000-0002-6461-1666?lang=en

Professor Chow Sek Chuen completed his Doctor of Medical Science degree in Immunology from the Karolinska Institute (Sweden) in 1990. After postdoctoral research work in cancer drug development at the Mayo Clinic and Foundation (US) he returned to the Karolinska Institute to develop immunotoxicology. Following that he joined the Medical Research Council (MRC) Toxicology Unit at Leicester University (UK) as a MRC fellow before taking up a lectureship at Nottingham University (UK). In 2002, he returned to the MRC Toxicology Unit as a Group Leader in Immunotoxicology.

Professor Chow joined the School of Science, Monash University Malaysia in 2007 as an Associate Professor with a co-appointment as an adjunct Associate Professor at the Department of Immunology, Faculty of Medicine, Nursing and Health Sciences, Monash University. He served as Deputy Head of School for research in 2008 and was appointed as Professor of Biomedical Sciences in 2011. As founding director, he launched the Malaysia Medicinal and Aromatic Plants (MyMAP) Accelerator in Monash University Malaysia with Agensi Inovasi Malaysia in 2011. He is one of the founding members of Malaysia Society of Toxicology (MySOT) and have served as Vice President (2010) and President (2012) for MySOT. In 2014 he was appointed as member of the Scientific Advisory Board of the Institute for Research, Development and Innovation (IRDI) at International Medical University, Malaysia.

Qualifications

  • Certificate in teaching tertiary education, Karolinska Institute, Sweden, 1994
  • Doctor of Medical Science in Immunology, Karolinska Institute, Sweden, 1990
  • Master in Biochemistry, Leeds University, 1986
  • Bachelor of Science (Biochemistry), Coventry University, 1982

Expertise

Immunotoxicology, mechanisms and regulation of apoptosis/program cell death in metazoans and protozoan parasite (Toxoplasma gondii), T lymphocyte biology and signaling.

Research Interests

Disruption of immunity by xenobiotics is known to have profound effects on immune function. My interest lies mainly in the understanding of how xenobiotics modulate the immune system, particularly on T lymphocytes function. T lymphocytes play an important role in the regulation of virtually all immune responses. Using various human and rodent model systems, the immunomodulatory effects of xenobiotics on many aspects of T cell biology are being investigated. All these processes have defined endpoints that are tightly regulated by signaling pathways, metabolic processes and enzyme cascades. Understanding how these molecular processes are affected by xenobiotics helps to provide a better understanding in the development of new strategies for therapeutic intervention for some immunological disorders.

Among these molecular processes, the mechanism and regulation of program cell death or apoptosis is a long-standing interest in my laboratory. In the immune system apoptosis plays a fundamental role in the normal development of lymphocytes, cytotoxic T lymphocyte and natural killer cell killing and maintenance of tissue homeostasis following immune responses. Because of this a number of diseases including most autoimmune diseases as well as AIDS are the direct result of either immunosuppression or hyperactivity of the immune system caused by inappropriate or deregulated apoptosis. In addition, many xenobiotics and infectious agents exert their immunotoxicity through the induction or inhibition of apoptosis in immune cells. Understanding these processes can provide insights into how some immunological diseases arise and offer opportunities to advance our knowledge on the molecular basis of infection and diseases in the immune system.

Another major interest is to understand the mechanisms of death and extracellular survival of the apicomplexa T. gondii.  Identification of the death effectors involved in the parasite death pathway can be exploited for anti-parasitic drug development to combat and eliminate parasites which cause widespread infections.

Teaching

  • IMM3802 (Essentials of Applied Immunology)
  • SCI3716 (Lab and Workplace Management)

Book chapters

Kass, G. E. N., Chow, S. C., and Orrenius, S. (2000) Apoptosis triggered by free radicals: Role in human diseases. In: Biomolecular Free Radical Toxicity: Causes and Prevention. Wiley Press.

Pritchard, D., Hooi, D., Watson, E., Chow, S., Telford, G., Bycroft, B., Chabra, S.R., Harty, C., Camara, M., Diggle, S. and Williams, P. Bacterial quorum sensing signal molecules as immune modulators. In “Bacterial evasion of host immune responses in Advances in Molecular and Cellular Microbiology (eds. B. Henderson and P. Oyston. ) (2003) Cambridge University Press.

Scholarly Journals

Rajah, T. and Chow, S.C. Suppression of Human T Cell Proliferation Mediated by the Cathepsin B Inhibitor, z-FA-FMK is due to oxidative stress (2015) PLOS One 10(4):e0123711

Rajah, T. and Chow, S.C. The inhibition of human T cell proliferation by the caspase inhibitor z-VAD-FMK is mediated through oxidative stress (2014) Tox. App. Pharmacol. 278:100-106

Liow, K.Y. and Chow, S.C. The cathepsin B inhibitor, z-FA-CMK is toxic and readily induced cell death in human T lymphocytes (2013) Tox. App. Pharmacol. 271, 559-567.

Lawrence, C. and Chow, S.C. Suppression of human T cell proliferation by the caspase inhibitors, z-VAD-FMK and z-IETD-FMK is independent of their caspase inhibition properties (2012) Tox. App. Pharmacol. 265, 103–112.

Romano Ngui, Liam Chong Kin, Chow Sek Chuen, Shukri Jaafar and Yvonne Lim Ai Lian. Association between anaemia, iron deficiency anaemia, neglected parasitic infections and socioeconomic factors in rural children of West Malaysia (2012) PLOS Neglected Tropical Diseases Volume 6, 3:e1550.

Romano Ngui, Saidon Ishak, Chow Sek Chuen, Rohela Mahmud, Yvonne A. L. Lim. Prevalence and Risk Factors of Intestinal Parasitism in Rural and Remote West Malaysia. (2011) PLOS Neglected Tropical Diseases 5:e974

Chow, S. C. Immunomodulation by statins: mechanisms and potential impact on autoimmune diseases (2009) Arch. Immunol. Ther. Exp.57, 243–251.

Lawrence, C., Kadioglu, A., Coward, W., Yang, A-L and Chow, S.C. The cathepsin B inhibitor, z-FA-FMK is an immunosuppressive peptide that inhibits T cell proliferation and modulates host response to Pneumococcal infection. (2006) J. Immunology 177:3827-3836.

Coward, W.R., Marei, A., Yang, A., Vasa-Nicotera, M., and Chow, S.C. Statin-induced proinflammatory response in mitogen-activated peripheral blood mononuclear cells through the activation of caspase-1 and IL-18 secretion in monocytes. (2006) J. Immunology 176:5284-5292.

Coward, W.R. and Chow S.C. Effect of atorvastatin on TH1 and TH2 cytokine secreting cells during T cell activation and differentiation. (2006) Atherosclerosis 186:302-309.

Holmstrom, T., Schmitz, I., Poukkula, M., Soderstrom, T., Johnson, V., Chow, S. C., Krammer, P., and Eriksson, J. MAPK/ERK signalling inhibits CD95-mediated apoptosis in activated T cells by inhibiting caspase-8 and Bid processing after DISC assembly. (2000) EMBO Journal 20:1-11.

Johnson, V. L., Ko, S. C. W., Holmstrom, T. H. , Eriksson, J. E. and Chow, S.C. Effector caspases are dispensable for the early nuclear morphological changes during chemical-induced apoptosis (2000) J. Cell Science. 113:2941-2953.

Chow, S.C., Brown, A., and Pritchard, D. I. The human hookworm pathogen Necater americanus induces apoptosis in T lymphocytes. (2000) Parasite Immunol. 22:21-29.

Holmstrom, T.H., Tran, S., Johnson, V.L., Ahn, N.G., Chow, S.C., and Eriksson, J.E. Inhibition of mitogen-activated kinase signaling sensitizes tumor cells to Fas receptor-mediated apoptosis. (1999) Mol. Cell Biol. 19:5991-6002.

Johnson, V.L., Cooper, I.R., Jenkins, J.R. and Chow, S.C. Effects of differential overexpression of Bcl-2 on apoptosis, proliferation and telomerase activity in Jurkat T cells. (1999) Exp. Cell. Res. 251:175-184.

Jones, R.A., Johnson, V.L., Buck, N.R., Dobrota, M., Hinton, R.H., Chow, S.C., and Kass, G.E.N. Fas-mediated apoptosis in mouse hepatocytes involves the processing and activation of caspases. (1998) Hepathology 27:1632-1642.

Holmström, T. H., Chow, S. C., Elo, I., Coffey, E., Orrenius, S., Sistonen, L. and Eriksson, J. Suppression of Fas/Apo-1-mediated apoptosis by the mitogen activated kinases ERK1/2. (1998) J. Immunol. 160: 2626-2636.

Leppa, S., Pirkkala, L., Chow, S.C., Eriksson, J., and Sistonen, L. Thioredoxin is transcriptionally induced upon activation of heat shock factor 2. (1997) J. Biol. Chem. 272: 30400-30404.

Chow, S.C., Kass, G.E.N., and Orrenius, S. Purines and their role in apoptosis. (1997) Neuropharmacology 36:1149-1156.

Kass, G. E. N, Eriksson, J., Weis, M., Orrenius, S., and Chow, S. C. (1996) Chromatin condensation during apoptosis requires ATP. Biochem. J. 318:749-752.

Slee, E. A., H. Zhu, Chow, S. C., M. MacFarlane, D. W. Nicholson, and G. M. Cohen. (1996). Benzyloxcarbonyl-Val-Ala-Asp (Ome) fluoromethylketone (Z-VAD-FMK) inhibits apoptosis by blocking the processing of CPP32. Biochem. J. 315:21-24.

Weis, M., Schlegel, J., Kass, G.E.N., Holström, T. M., Peters, I., Eriksson, J., Orrenius, S., and Chow, S. C. Cellular events during Fas/APO-1-induced apoptosis in JURKAT T lymphocytes. (1995) Exp. Cell Res. (1995) 219:699-708.

Chow, S. C., Weis, M., Kass, G.E.N., Holström, T. M., Peters, I., Eriksson, J., Orrenius, S. Involement of multiple proteases during Fas-mediated apoptosis in T lymphocytes. (1995) FEBS Letters 364:134-138.

Chow, S.C., and Orrenius, S. Rapid modification of cytoskeleton in thymocytes induced by the immunotoxicant, tributyltin. (1994) Toxicol. Appl. Pharmacol. 127:18-25.

Jiang,S-I., Chow, S.C., Nicotera, P., and Orrenius, S. Increase in cytosolic free Ca2+ concentration is a signal for the initiation of apoptosis: Studies using the microsomal Ca2+-ATPase inhibitor thapsigargin. (1994) Exp. Cell Res. 212:84-92.

Chow, S. C., Kass, G.E.N., McCabe, M. and Orrenius, S. Tributyltin increases cytosolic free Ca2+ concentration in thymocytes by mobilizing intracellular Ca2+, activating a Ca2+ entry pathway and inhibiting Ca2+ efflux. (1992) Arch. Biochem. Biophys. 298:241.

Kass, G.E.N., Llopis, J., Chow, S.C., Duddy, S.K. and Orrenius, S. Receptor‑operated calcium influx in rat hepatocytes: Identification and characterization using manganese. (1990) J. Biol. Chem. 265:17486‑17492.

McConkey, D. J., Chow, S. C., Orrenius, S. and Jondal, M. NK cell induced cytotoxicity is dependent on a Ca2+increase in the target. (1990) FASEB 4:2661‑2664.

McConkey, D.J., Hartzell, P., Chow, S.C., Orrenius, S. and Jondal, M. Interleukin‑1 inhibits calcium stimulated, T‑cell receptor dependent endonuclease activation in mature thymocytes. (1990) J. Biol. Chem. 265:3009‑3011.

Chow, S. C. and Jondal, M. Polyunsaturated free fatty acids stimulate an increase in cytosolic free calcium by mobilizing the inositol 1,4,5‑trisphosphate sensitive calcium pool in T‑cells through a mechanism independent of phosphoinositide turnover. (1990) J. Biol. Chem. 265:902‑907.

Chow, S. C., Sisfontes, L., Björkhem, I. and Jondal, M., Suppression of growth in a leukaemic T‑cell line by n‑3 and n‑6 polyunsaturated fatty acids (1989) Lipids 24(8): 700‑704.

Chow, S. C., Ng, J., Norstedt, C., Fredholm, B.B. and Jondal, M., Phosphoinositide breakdown and evidence for protein kinase C involvement during human NK killing (1988) Cell. Immunol.114: 96‑103.

Research Grants

  • Dr Nafees Ahemad Muhammed Yunus ,Dr Anna Dolchenko, Prof Chow Sek Chuen, Prof Ieksan Bin Othman & Dr Anton Dolzhenko, 2015, Synthesis Of 5-Azapurine Derivatives As New Modulators Of Purinergic Receptors, FRGS, RM152k
  • Assoc. Prof. Fang Chee Mun, Prof. James Galen, Prof Chow Sek Chuen & Prof Sheila Nathan, 2015, Development of enhanced fitness Salmonella live vector carrier vaccine by using Toxoplasma gondii antigens as a model candidate, MOSTI, RM271k
  • Dr Anton Dolzhenko, Prof Chow Sek Chuen, 2015, Heterocyclic purine analogues: xanthine oxidase substrates or inhibitors?, FRGS, RM83k
  • Dr Lee Wai Leng & Prof Chow Sek Chuen, 2014, Oncogenic Mutation Regulates Immunosuppression and Drug Resistance via Tumor-derived Exosomes, FRGS, RM170k
  • Prof Chow Sek Chuen, Dr Lim Siew Peng, 2013, Characterization of the molecular mechanisms of apoptotic-like death in Toxoplasma gondii tachyzoites during oxidative stress, MOSTI, RM213k
  • Dr Lee Learn Han, AP Fang Chee Mun & Prof Chow Sek Chuen, 2013, Role of Interferon Regulatory Factor 5 (IRF-5) in the Regulation of Interleukin 13 (IL-13), a Key Mediator of Allergic Asthma, FRGS, RM150k
  • Dr Allan lee & Prof Chow Sek Chuen, 2013, Deciphering the mechanisms of tumor suppressor effects of semaphorin 5A in human gliomas, FRGS, RM150k

PhD students (Current)

  1. Yeo Eng Hwa
  2. Athena Ng Xin Hui
  3. Ding Zhen Shern
  4. Md. Moinul Hoque
  5. Cheong Poi Yee

PhD students (Completed)

  1. Tanuja Rajah (2015)
  2. Yee Choy Chew (2014)
  3. Lee Woon Ching (2014)
  4. Girija Thiruvengadam (2012)
  5. Low Kit Yee (Co-supervision) (2015)
  6. Qingwen Chen (Co-supervision) (2014)

Honours students (Current)

  1. Tammy Tan Xing Mei

Honours students (Completed)

  1. Ding Zhen Shern
  2. Ho Jia Min
  3. Alvin Tang Wei Jie

3rd Year Project

  1. Yeo Li-Fang

Professional Association

Professional membership

  • UK Register of Toxicologist, Institute of Biologist & British Society of Toxicologist, 2006
  • European Register Toxicologist, Federation of European Society Toxicologist, 2006
  • Chartered Biologist, Institute of Biologist, 1990
  • Malaysia Society of Toxicology, Vice President, 2010-2012, 2015 to present
  • Malaysia Society of Toxicology, President, 2012-2015

Membership in Academic Editorial Committees

  • Toxicology and Applied Pharmacology, Associate Editor, 2013 to present
  • Toxicology and Applied Pharmacology, Editorial Board, 2002-2012

Patents

  • European Patent No: EP 9900930.0 (1999), EP 1140122 (2004) (Title: Pro-apoptotic agents from the human hookworm, Necater Americanus).
  • World Patent No: WP 2000041706 (2000) (Title: Pro-apoptotic agents from the human hookworm, Necater Americanus).
  • US Patent No: US 20040058017A1 (2003), US 20070009504A1 (2006) (Title: Pro-apoptotic agents from the human hookworm, Necater Americanus).