Associate Professor Chow Sek Chuen

Associate Professor

Area of Expertise
Research Interest
Selected Journals
Book Chapters
Patent
Current Research Projects
Research Students
Research Assistants
Plenary/Keynote Lectures

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 and their function. The T lymphocytes constitute one of many cellular components in the immune system and 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, such as development, activation, differentiation, cellular homeostasis and apoptosis 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 apoptosis is a long-standing interest in my laboratory. In the immune system apoptosis plays a fundamental role in the normal development of lymphocytes, killing processes mediated by cytotoxic T lymphocytes and natural killer cells and maintenance of tissue homeostasis during the termination of immune responses. Because of this a number of diseases including most autoimmune and graft versus host 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. This applies not only to immunological diseases but also to cancer and neurodegenerative diseases.

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

Coward WR, Marei A, Yang A, Vasa-Nicotera M, Chow SC (2006) Statin induced proinflammatory response in mitogen-activated peripheral blood mononuclear cells through the activation of caspase-1 and IL-18 secretion in monocytes. J Immunol 176:5284-5298

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

Lawrence PC, Chow SC (2005) FADD deficiency sensitises Jurkat T cells to TNF-α dependent necrosis during activation-induced cell death. FEBS Lett 579:6465-6472.

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

Johnson VL, Ko SCW, Holmstrom TH, Eriksson JE, Chow SC (2000) Effector caspases are dispensable for the early nuclear morphological changes during che mical-induced apoptosis. J Cell Sci 113:2941-2953

Chow SC , Brown A, Pritchard DI (2000) The human hookworm pathogen Necater americanus induces apoptosis in T lymphocytes. Parasite Immunol 22:21-29

Holmstrom TH, Tran S, Johnson VL, Ahn NG, Chow SC, Eriksson JE (1999) Inhibition of mitogen-activated kinase signaling sensitizes tumor cells to Fas receptor-mediated apoptosis. Mol Cell Biol 19:5991-6002

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

Pritchard D, Hooi D, Watson E, Chow SC, Telford G, Bycroft B, Chabra SR, Harty C, Camara M, Diggle S, Williams P (2003) Bacterial quorum sensing signal molecules as immune modulators. In: Henderson B, Oyston PCF (ed) Bacterial evasion of host immune responses. Cambridge University Press, Cambridge, UK, pp 201-222

Kass GEN, Chow SC ,Orrenius S (2000) Apoptosis triggered by free radicals: Role in human diseases. In: Wiseman H, Goldfarb P, Ridgway T, Wiseman A (eds) Biomolecular free radical toxicity: Causes and prevention. Wiley Press, Chichester, UK, pp 145-168

• Characterization of the molecular mechanisms involved in the activation of caspase-1 through the inhibition of isoprenoid biosynthesis in monocytes.

• Toxicity of peptide-based Cathepsin inhibitors in tumor cells and its potential anti-cancer properties.
  
• Epidemiological distribution of helminth infection and asthma in the Orang Asli communities in Peninsula Malaysia.

Honours students ( Present)

1. Dimuthu De Silva - Mechanism of toxicity and potential anti-cancer properties of z-FA-CMK in different cell lines.
2. Suzan Saidin – Expression, production and bioactivity characterization of the human receptor (Fas/CD95) fused to the heavy chain (Fc) of human IgG.
3. Madhulika Ravichandran - Structure Activity Studies on Apoptosis Inducing Short Peptides in T Lymphocytes
4. Yee Mei Qi – Studies on the immunomodulatory and anti-cancer effects of Alpinia galangal extracts.
5. Eveline - Effect of overexpression of the anti-apoptotic proto-oncogene, Bcl-2 and the deletion of apoptotic signalling proteins, FADD and caspase-8 on cell death induced by the dipeptide, benzyolcarbonyl-Phe-Ala-chloromethylketone (z-FA-CMK) in human T lymphoma cells.

Honours students ( Past)

1. Low Kiat Yee – Mechanism of toxicity and potential anti-cancer properties of Benzyolcarbonyl-Phe-chlolomethylketone (z-F-CMK) in tumor cells.
2. Tanujah Rajah – Studies on the mechanism of toxicity and potential anti-cancer properties of Benzyolcarbonyl-Leu-chlolomethylketone (z-L-CMK) in tumor cells.

Postgraduate students ( Present )

• Ho Hooi Ling(PhD) - Role of p63 in cell cycle progression and apoptosis in mature skin stem cells.
• Bassam M. Hassan (PhD- joint supervision with University Malaya) - Hookworm infection as a protective factor against the development of asthma in the indigenous people in rural areas in Malaysia.
1. Romano Ngui (MSc-joint supervision with University Malaya) - Epidemiological study of soil-transmitted helminthes infection and prevalence of asthma cases among orang asli in Malaysia.

1. Sue Mei Jean - Characterization of the molecular mechanisms involved in the activation of caspase-1 through the inhibition of isoprenoid biosynthesis in monocytes.
2. Tanuja Rajah - Characterization of the molecular mechanisms involved in the activation of caspase-1 through the inhibition of isoprenoid biosynthesis in monocytes.
3. Jimmy Thoo Wei Yang – Optimising the bioconversion of lignocellulose materials in oil palm fruit bunches to ethanol.

Plenary Lecture
Immune evasion and modulation by human hookworm – 44 th Annual Scientific Seminar Malaysian Society of Parasitology and Tropical Medicine (4- 5 th March 2008)