Our mission is to identify and gain insights from the genetic and molecular pathways involved in cardiovascular disorders
The main objective of our research program is to broaden our understanding of the cellular and molecular mechanisms involved in blood vessel wall patterning and define the role of these pathways in vascular abnormalities and complications, and then link these insights to translational research to improve the prevention and treatment of human cardiovascular disease. To this end, we employ a unique blending of mouse models, cultured cells as well as human samples, that are aimed at unveiling the pathogenesis of cardiovascular diseases. Our ultimate goal is to prevent and reverse vascular disease to prevent heart attack and stroke.
What impact will this research have?
Currently available cardiovascular therapies are not universally effective and do not reverse the vascular disease completely, therefore vascular diseases place a heavy burden on the health care system. Our ultimate mission is to identify the factors and signalling mechanisms that may provide better therapeutic options to eradicate cardiovascular disease.
Current projects and goals
Cardiovascular disease is the main cause of death globally, accounting for approximately one third of all deaths. Vascular diseases such as atherosclerosis, stroke and arterial injury involve reassertion of developmental pathways suggesting that cellular and molecular pathways that play critical roles in normal development may be involved in disease progression in adult life. Our goal is to gain critical insight from these pathways and manipulate them to develop novel therapeutic strategies. In particular, we are investigating how blood vessels undergo remodeling, repair, regression and de novo vascularization. We are using a range of techniques including lineage tracing, fate mapping and high resolution microscopy to investigate fundamental biological processes such as cell migration, cell proliferation and fate change at single cell level.
The role of Notch signalling in cardiovascular disease and related pathologies
Notch has been comprehensively studied as a conciliator of cell-to-cell communication that mediates cell fate decisions of progenitors. While Notch signalling has been extensively studied in cell fate determination at distinct development stages of mammalian cells as well as cancer stem cell progenitor maintenance and renewal, the functional role of Notch signalling in vascular wall patterning and cardiovascular disease is not well understood. By using advanced microscopic techniques, fate mapping approaches and single cell clonal analysis, we aim to study the role of Notch signalling in blood vessel wall patterning and maintenance of smooth muscle cell progenitors in developing walls as well as disease of the vasculatures. Thus, we believe that the investigation of Notch signalling in vascular biology promises to be a very fruitful way forward to designing new therapeutics.
Factors and regulators of smooth muscle cells and macrophages in progression of atherosclerosis
Atherosclerosis is a leading cause of death worldwide. Atherosclerotic plaque or atheroma consist of smooth muscle cells (SMCs) and macrophages in the malefactor lesion and are comprised of a lipid-laden core covered by a fibrous cap. Plaque rapture leads to thrombosis with dire consequences, such as myocardial infarction and stroke. SMCs and macrophages are key players in atherogenesis. Although extensive research has been done in the past on atherosclerosis, exactly how cells from normal blood vessel walls contribute to atherosclerotic plaques is still far from clear. Our studies aim to discover the origin of the cells that make normal blood vessels and how these cells contribute to atherogenesis. Recently, our studies established that very few SMCs have the potential to migrate and proliferate from the blood vessels and produce most of the SMCs in atherosclerotic plaques. The focus of our current studies is to identify new signalling molecules, factors and/or pharmacological inhibitors that can modulate SMC phenotypic switching and macrophage infiltration into the plaque to change the plaque composition and thereby promote plaque stability.