Prof Jelena Mann

About

Liver fibrosis is a final common pathway of liver injury irrespective of aetiology. It is characterised by progressive replacement of normal hepatic tissue with collagen-rich scar tissue and is responsible for around 1.5 million death per annum worldwide. There are no proven effective therapeutics for fibrosis, the only treatment available for chronic liver disease is transplantation which is limited by availability of donor organs. 

I am interested in delineating epigenetic signalling pathways that trigger fibrogenesis and in doing so, discovering molecular control of fibrogenesis and associated signalling pathways that can be targeted with new as well as existing drugs. More recently we have also embarked on studies that test the ability of environmental factors to affect transgenerational inheritance of predisposition to liver fibrosis. Adaptation to environmental insults is critical for ensuring fitness and survival of the species, however it is currently not clear if predisposition to development of fibrosis exists or indeed if existence of disease in previous generations alters such predisposition.

We have published the first report of the transgenerational epigenetic transmission of protection against liver fibrosis which provides evidence of heritable mechanisms for the rapid adaptation of animals to environmental insults. The lab is now carrying out further characterisation of this newly reported phenomena and its impact on liver disease of various aetiology.

Education

• 1994-1997 - BSc Biochemistry, 1st class
• 1997-2001 - PhD in Medicine, University of Southampton

Previous appointments

• University of Leeds, Postdoctoral Research Assistant (31/01/2001 to 31/12/2002)
• Wellcome Trust Postdoctoral Research Assistant, University of Southampton (01/01/2003 to 31/08/2004).
• University of Southampton Personal Fellowship 01/09/2004 to 01/10/2006

Editorial boards

• American journal of Physiology : Gastrointestinal and Liver Physiology

Prizes

• Best talk prize, British Association for study of liver annual meeting, 2007
• Best abstract prize, British Association for study of liver annual meeting, 2008
• September 2010, Dame Sheila Sherlock Young Investigator Research Medal - single annual award for outstanding research contributions in the field of Hepatology

Patents

• United Statesprovisional application serial nos. US61/206,774, filed February 4, 2009, entitled "Methods of Inhibiting Liver Fibrogenesis and Treating Liver Damage, Including Cirrhosis of the Liver" and 61/277,284, filed September 22, 2009, entitled "Methods of Inhibiting Fibrogenesis and Treating Fibrotic Disease"

Major Publications

• Page A, Paoli P, Moran Salvador E, White S, French J, Mann J - Hepatic stellate cell transdifferentiation involves genome-wide remodeling of the DNA methylation landscape.
• Hardy T, Zeybel M, Day CP, Dipper C, Masson S, McPherson S, Henderson E, Tiniakos D, White S, French J, Mann DA, Anstee QM, Mann J - Plasma DNA methylation: a potential biomarker for stratification of liver fibrosis in non-alcoholic fatty liver disease.
• Wilson CL, Jurk D, Fullard N, Banks P, Page A, Luli S, Elsharkawy AM, Gieling RG, Chakraborty JB, Fox C, Richardson C, Callaghan K, Blair GE, Fox N, Lagnado A, Passos JF, Moore AJ, Smith GR, Tiniakos DG, Mann J, Oakley F, Mann DA - NFκB1 is a suppressor of neutrophil-driven hepatocellular carcinoma.
• Page A, Paoli PP, Hill SJ, Howarth R, Wu R, Kweon SM, French J, White S, Tsukamoto H, Mann DA, Mann J - Alcohol directly stimulates epigenetic modifications in hepatic stellate cells.
• Perugorria MJ, Murphy LB, Fullard N, Chakraborty JB, Vyrla D, Wilson CL, Oakley F, Mann J, Mann DA - Tumor progression locus 2/Cot is required for activation of extracellular regulated kinase in liver injury and toll-like receptor-induced TIMP-1 gene transcription in hepatic stellate cells in mice.
• Perugorria MJ, Wilson CL, Zeybel M, Walsh M, Amin S, Robinson S, White SA, Burt AD, Oakley F, Tsukamoto H, Mann DA, Mann J - Histone methyltransferase ASH1 orchestrates fibrogenic gene transcription during myofibroblast transdifferentiation.
• Zeybel M, Hardy T, Wong YK, Mathers JC, Fox CR, Gackowska A, Oakley F, Burt AD, Wilson CL, Anstee QM, Barter MJ, Masson S, Elsharkawy AM, Mann DA, Mann J - Multigenerational epigenetic adaptation of the hepatic wound-healing response.
• Ebrahimkhani MR, Oakley F, Murphy LB, Mann J, Moles A, Perugorria MJ, Ellis E, Lakey AF, Burt AD, Douglass A, Wright MC, White SA, Jaffré F, Maroteaux L, Mann DA - Stimulating healthy tissue regeneration by targeting the 5-HT₂B receptor in chronic liver disease.
• Mann J, Chu DC, Maxwell A, Oakley F, Zhu NL, Tsukamoto H, Mann DA - MeCP2 controls an epigenetic pathway that promotes myofibroblast transdifferentiation and fibrosis.
• Elsharkawy AM, Oakley F, Lin F, Packham G, Mann DA, Mann J - The NF-kappaB p50:p50:HDAC-1 repressor complex orchestrates transcriptional inhibition of multiple pro-inflammatory genes.
• Mann J, Oakley F, Akiboye F, Elsharkawy A, Thorne AW, Mann DA - Regulation of myofibroblast transdifferentiation by DNA methylation and MeCP2: implications for wound healing and fibrogenesis.