Professor Dipak Ramji
Research interests focus on understanding the molecular mechanisms underlying the changes in key cellular processes during inflammatory disorders with the goal of identifying new therapeutic/preventative targets/avenues. Research employs a combination of cell culture and mouse model systems coupled with molecular, biochemical, immunological and pharmacological approaches. Specific focus is on understanding how key factors associated with inflammatory disorders, such as cytokines and lipid metabolites, regulate macrophage processes and gene expression during atherosclerosis and the acute-phase response. In particular, we are elucidating the pathways leading from the interaction of such factors with their receptors, through the signalling cascades, to the control of gene expression in the nucleus and the subsequent regulation of cellular processes. More recently, the mechanisms underlying the protective actions of nutraceuticals in atherosclerosis and key cellular processes associated with this disease are being investigated. Previous and current research has been funded by grants from the British Heart Foundation, Wellcome Trust, BBSRC, MRC, EU and Industry.
I did my BSc (Hons) in Biochemistry and PhD on Dictyostelium development at University of Leeds. This was followed by postdoctoral research at the European Molecular Biology Laboratories (Heidelberg) and Istituto di Ricerche di Biologia Molecolare "P. Angeletti" (Rome) on the molecular mechanisms underlying liver-specific gene expression during inflammation. I was recipient of fellowships from the Royal Society, EMBL, University of Rome and the EU. I moved to Cardiff University as a Lecturer in August 1992. I was promoted to a Senior Lecturer in 2003, to a Reader in 2006 and to a Personal Chair in 2017.
The overall aim of research in my laboratory is to understand how cytokines and other disease-associated factors regulate key cellular processes during inflammatory disorders with the goal of identifying new therapeutic/preventative targets/avenues. 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 and the subsequent regulation of cellular processes. Research uses a combination of cell culture and mouse model systems coupled with molecular, biochemical, immunological and pharmacological approaches. Previous and current research has been funded by grants from the British Heart Foundation, Wellcome Trust, BBSRC, MRC, EU and Industry. Our research is focused on three major areas:
Regulation of macrophage processes during atherosclerosis
Atherosclerosis and its complications, such as myocardial infarction and cerebrovascular accident, are responsible for more deaths worldwide than any other disease. Atherosclerosis is an inflammatory disorder of medium and large arteries (Figure 1) orchestrated by cytokines. Macrophages play a prominent role in the pathogenesis of this disease with their uncontrolled uptake of atherogenic lipoproteins and subsequent transformation into foam cells representing a critical early step in atherogenesis (Figure 2). A major focus of research in my laboratory is devoted to understanding the molecular mechanisms by which cytokines regulate key macrophage processes during atherosclerosis. Specific focus is on the actions of interferon-gamma, transforming growth factor-beta and interleukin-33.
Nutraceuticals in the prevention and treatment of atherosclerosis
Current pharmaceutical therapies against atherosclerosis are associated with considerable residual risk for cardiovascular disease together with other issues such as side effects and patient-dependent efficacy. In addition, many drug discovery programs have failed to find alternatives. Nutraceuticals represent promising agents either for the prevention of atherosclerosis or treatment of the disease in conjunction with pharmaceutical agents (see Figure 3). However, this requires an in-depth understanding of their mechanisms of actions and ultimately large clinical trials to test their efficacy. We are investigating the anti-atherogenic actions of several nutraceuticals, including dihomo-gamma-linolenic acid, gamma-linolenic acid, omega-3 fatty acids, hydroxytyrosol, catechin, phytosterols and probiotics.
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 (acute phase response) was the focus of my post-doctoral research and has been continued at Cardiff. In addition, the studies have been extended to cytokine-regulated expression of the C/EBP family in several other inflammatory disorders.
Previous and Current External Activities
- Expert Evaluator and Panel Member for Horizon 2020 (2015); BBSRC Pool of Experts (2009-2010); member of the MRC Advisory Board (2004-2005); and Panel member of IRCSET (Ireland) Postdoctoral Fellowship Scheme Assessment Committee(2007-2008; Chair in 2008).
- Scientific Advisory Board of the International Academy of Cardiology.
- Science Committee Member for the 16th Euro Fed Lipid Congress, Belfast 2018.
- Organising Committee Member for Annual Conference on Atherosclerosis & Clinical Cardiology, Philadelphia (2016) and 13th International Conference on Pathology and Molecular Diagnosis, San Diego (2017).
- Editorial Board Member of 16 International Journals.
- External Examiner for BSc in Biochemistry at Kings College London (2016-2020) and BSc in Biological Sciences at University of Reading (2015-2019). Previous External Examiner for BSc in Biological Sciences at University of Huddersfield (2013-2017) and taught MSc programmes at Sheffield Hallam University (2006-2011).
- Track Chair, Session Chair and Poster Evaluator at many International Conferences.
- Extensive engagement activities for the British Heart Foundation (e.g. BHF Supporter’s Conference).
- Prof. Foo Liew (FRS), University of Glasgow
- Prof. Thomas Decker, Max F. Perutz Laboratories, Vienna
- Prof. Shinji Takai, Osaka Medical School
- Profs. Sammy Boussiba and Inna Khozin-Goldberg, Ben-Gurion University
- Drs. Frank Flider and Riccardo LoCascio, Arcadia Biosciences
- Drs. Daryn Michael, Tom Davies and Sue Plummer, Cultech Ltd
- Dr. Rob Winwood, DSM Nutraceuticals
- Dr Jason Johnson, Bristol Heart Institute
- Prof. Jonathan Napier and Dr. Olga Sayanova, Rothamsted Research
- Dr. Nigel Pearce, GlaxoSmithKline
- Dr. Ahmed Ali, International Gums & Oils Limited
- Prof. Gavin Wilkinson, and Drs Timothy Hughes, John Martin, Tim Bowen, Eddie Wang and Ian Humphreys, School of Medicine, Cardiff
- Prof. John Harwood and Drs Alvin Kwan and Irina Guschina, School of Biosciences, Cardiff