Department of Microbiology, NUS
Immunology Programme, NUS
Tel: +65 6516 7207
Increasing evidence in the literature suggests that the lymphatic system is not an inert but rather plastic system which plays an important role in immunity and inflammation. Having shown a few years ago that inflammatory signals present in a strong adjuvant can induce the remodeling of lymphatic vessels within inflamed lymph node, we are currently investigating further the molecular and cellular events involved in regulating lymphatic vessel remodeling under inflammation. Understanding how lymphatic vessel function may affect the adaptive immune response and the resolution of inflammation is another focus of our work. In this context, we discovered recently an unexpected role for neutrophils in supporting the growth of lymphatic vessels, namely lymphangiogenesis, in peripheral tissue such as the skin and lymph nodes during inflammatory conditions (1). Our work also provides further evidence that lymphatic vessels can modulate the immune response by regulating the trafficking of immune cells including lymphocytes and dendritic cells. Finally, we found that the function of lymphatic vessel is not limited to support the migration of immune cells but it is also critical for the transport of lipids and particularly cholesterol (2). Indeed, we found that in absence of functional lymphatic vessels, cholesterol transport from peripheral tissues back to the liver and bile is significantly impaired, and as a consequence, cholesterol accumulates in peripheral tissues. More importantly, we showed that this lymphatic transport of cholesterol is mediated by the transporter scavenger receptor class B type I on lymphatic endothelial cells which challenges the current view of lymphatic endothelium as a passive barrier. We are now investigating the clinical relevance of our findings.
Atherosclerosis is a systemic disorder of the large and medium-sized arterial vessels, affecting the coronary, cerebral and peripheral circulation. Chronic inflammation is the central pathophysiological mechanism and provides the substrate for occlusive thrombus formation in which platelets are a key player in the initiation and progression of atherothrombosis1. The clinical complications of acute arterial thrombosis, heart attack and stroke, are the most common causes of morbidity and mortality in the industrialized countries including Singapore. Limitations of currently available anti-platelet agents highlight the need to develop additional therapies with novel properties and molecular targets, which will ideally confer maximal protection against cardiovascular events whilst preserving sufficient platelet haemostatic function to minimize bleeding complications. Recently, we have identified a new factor expressed by platelets and we are currently investigating whether it represents a novel molecular target for arterial thrombosis and evaluating its potential and lead clinical applications in close collaboration with Dr Chan, Y.Y from Cardiovascular Research Institute, NUHS.
|2008 - 2011||Contribution of lymphatic function in atherosclerosis and its modulation by lipid mediators||BMRC|
|2008 - 2011||Identification of the molecular and cellular mechanisms altering dendritic cell motility during atherosclerosis||NMRC|
|2009 - 2011||Role of bone-marrow derived cells in tumor-induced lymph node lymphangiogenesis in a mouse model of human melanoma and its significance in human cancer dissemination||SIgN|
|2010 - 2015||Lymphatic function in inflammation resolution||NRF|
|2011 - 2014||Promoting effective lymphatic drainage of the arteries as a new therapeutic intervention for atherosclerosis||NMRC|
|2011 - 2014||Regulation of lymph node lymphangiogenesis by neutrophilic myeloid cells and its potential therapeutic benefit in inflammation and cancer||BMRC|