Dr Dipak Ramji
Photos of coronary arteries.
The overall aim of research in my laboratory is to understand comprehensively how specific factors, such as cytokines and lipid metabolites, regulate gene expression during health and disease. In particular, we are elucidating the pathways leading from the interaction of such factors with their receptors, through the intracellular signalling cascades, to the control of gene expression in the nucleus. Previous and current research has been funded by grants from the Wellcome Trust, BBSRC, British Heart Foundation, MRC and GlaxoSmithKline. Our research is focused on two major areas:
Regulation of macrophage gene expression during atherosclerosis
Drawing of molecular structure.
Atherosclerosis and its complications, such as coronary heart disease and stroke, are directly responsible for over 50% of all deaths in the Western world. Macrophages play a prominent role in the pathogenesis of the disease, with their uncontrolled uptake of atherogenic lipoproteins and their subsequent transformation into foam cells representing a critical early step in atherogenesis. The products of several genes contribute, either directly or indirectly, to lipoprotein metabolism and foam cell formation. The regulation of such genes by factors that are known to be present in the atherosclerotic lesion, such as cytokines, growth factors, chemotactic factors and modified lipoproteins is, therefore, likely to make a major contribution to the initiation and the progression of the disease. A major focus of research in my laboratory is devoted to understanding both the signal transduction pathway(s) and the transcriptional/post-transcriptional control mechanisms by which such factors modulate the expression of key genes in macrophages implicated in the regulation of foam cell formation, including lipoprotein lipase, apolipoprotein E, ATP-binding cassette transporter-A1, and liver X receptors. Such studies are expected to increase our understanding of the molecular basis of foam cell formation and atherosclerosis and, in the longer term, to identify potentially novel targets for therapeutic intervention.
Regulation of transcription factors belonging to the CCAAT/enhancer binding protein (C/EBP) family
Regulation of transcription factors belonging to the CCAAT/enhancer binding protein (C/EBP) family.
The C/EBP family plays a key role in the control of cellular growth and differentiation, and the pathogenesis of several diseases. The regulation of these factors during both physiological and pathophysiological conditions has hitherto been poorly understood. The regulation of the C/EBP family during inflammation in the liver was the focus of my post-doctoral research and has been continued at Cardiff. In addition, several projects have been initiated to delineate the mechanisms by which cytokines regulate the expression of the C/EBP family during a number of other inflammatory conditions.
British Heart Foundation
Dr. Simon K. Jackson School of Medicine, Cardiff University
Dr Nigel Pearce GlaxoSmithKline, Stevenage
Dr. David S. Leake University of Reading
Dr. Tim Bowen School of Medicine, Cardiff University
Dr. Feray Kockar University of Balikesir
Diagram of regulation of macrophage gene expression.