Dr Prakash Ramachandran
To study immune regulation of organ fibrosis with a view to identifying novel anti-fibrotic therapeutic approaches.
- Li Jia - PhD student (CSC funded)
- Eleni Papachristoforou - PhD Student (MRC DTP Precision medicine)
- Ravinder Parhar - PhD student (MRC DTP Precision medicine)
- Dr Sebastian Wallace - Clinical Research Fellow (co-supervisor)
Organ fibrosis (or scarring) is estimated to contribute to 45% of deaths in the Western world. However, there are currently no effective anti-fibrotic therapies. Fibrosis is the result of a complex multi-cellular response to chronic injury, which invariably incorporates the activation of immune cells within the damaged organ. By understanding the biology of the immune response in scar formation and scar resolution, novel treatments could be developed to treat patients with fibrotic diseases.
Our research is focused on understanding the role of the innate immune system in fibrosis and fibrosis resolution in the liver and other organs. In particular, cells of the monocyte/macrophage lineage have been shown to be key orchestrators of tissue scarring, and hence represent an attractive therapeutic target. However, macrophages are heterogeneous plastic cells, with multiple subpopulations of varied origin and phenotype. In order to develop effective anti-fibrotic therapies which can modulate macrophage function, it is imperative to fully understand macrophage heterogeneity.
To address this, we employ cutting-edge techniques (including single-cell RNA-seq, spatial transcriptomics, multiparameter flow cytometry and imaging) to study a range of primary human samples and fibrosis models. We recently defined a novel population of pathogenic macrophages in the fibrotic niche of fibrotic human liver tissue (Nature, 2019) and are now actively working to identify approaches to selectively inhibit the function of these macrophages and reduce tissue scarring.
I undertook medical training and an intercalated BSc (hons) in Pharmacology at the University of Edinburgh, graduating in 2003. I subsequently completed a Wellcome Trust funded PhD at the MRC Centre for Inflammation Research, under the supervision of Professor John Iredale, Professor Stuart Forbes and Dr David Kluth. I proceeded to finish my specialty clinical training in hepatology, gastroenterology and general medicine, working in both Edinburgh and Aberdeen. I was awarded an MRC Clinician Scientist Fellowship in 2015, entitled “The Role of Tissue-resident Hepatic Macrophages in the Resolution of Chronic Liver Injury”. The work during this Fellowship has provided several new insights into the biology of macrophages in fibrosis.
Honorary Consultant Hepatologist, Royal Infirmary of Edinburgh
Dr Eleni Sutherland - Postdoctoral Research Assistant
Honours and Awards
- 2020 Emerging Leader Award, European Association for the Study of the Liver (EASL)
- 2020 Sir Francis Avery Jones Research Medal, British Society of Gastroenterology (BSG)
- 2020 Rising Star Award, United European Gastroenterology (UEG)
- 2019 Dame Sheila Sherlock Research Prize, British Association for the Study of the Liver (BASL)
- 2015 Clinician Scientist Fellowship, MRC
- 2011 Travel award, British Association for the Study of the Liver (BASL)
- 2011 Young investigator award, European Association for the Study of the Liver (EASL)
- 2011 Young investigator award and oral presentation at plenary session, EASL
- 2011 1st prize in oral plenary session and Pushpa Chopra award at Medical Research Society/Academy of Medical Sciences Clinician Scientists in Training annual meeting
- 2008 Research Training Fellowship, Wellcome Trust
- Professor William Alazawi, Blizard Institute, Queen Mary University of London
- Dr Jenna Cash, Centre for Inflammation Research, University of Edinburgh
- Dr Bryan Conway, Centre for Cardiovascular Science, University of Edinburgh
- Dr Laura Denby, Centre for Cardiovascular Science, University of Edinburgh
- Dr Donald Dunbar, Edinburgh Genomics, University of Edinburgh
- Professor Jonathan Fallowfield, Centre for Inflammation Research, University of Edinburgh
- Professor Neil Henderson, Centre for Inflammation Research, University of Edinburgh
- Dr Tim Kendall, Centre for Inflammation Research, University of Edinburgh
- Professor Damian Mole, Centre for Inflammation Research, University of Edinburgh
- Dr Thomas Otto, Institute for Infection, Immunity and Inflammation, University of Glasgow
- Professor Jeffrey Pollard, MRC Centre for Reproductive Health, University of Edinburgh
- Dr Chris Weston, Institute of Immunology and Immunotherapy, University of Birmingham
Sources of Funding
- Medical Research Council
- Wellcome Trust
- Guts UK
- Kidney Research UK