Dr Matthew Hepworth

Matthew Hepworth – Research summary

Chronic inflammatory diseases, such as inflammatory bowel disease (IBD) and asthma, constitute a significant global economic and public health burden. Epidemiologic, genetic and immunologic studies implicate dysregulated adaptive immune cell responses, driven by otherwise harmless environmental antigens, in the pathogenesis of these disorders. In order to maintain tissue health and homeostasis at mucosal barrier sites, such as the intestine and lungs, the adaptive immune system must be tightly regulated.

hepworth

Matthew Hepworth

My research programme focuses on understanding the innate immune pathways that act to regulate inflammation at mucosal barrier tissue sites. Cells of the innate system play key roles in interpreting cues from the tissue microenvironment in order to educate the adaptive immune system. Recent reports in mice and humans have identified subsets of innate lymphoid cells (ILCs) as key mediators of inflammation, immunity and tissue repair at mucosal barrier surfaces through the production of effector cytokines. Moreover, changes in the frequency and function of ILCs are associated with inflammatory disorders in humans, suggesting targeting of ILC pathways may be of clinical relevance. Recently, a growing body of evidence indicates ILCs also have novel antigen presenting roles, via the expression of MHCII, thus implicating ILCs as critical regulators of adaptive immune cell-driven inflammation and immunity.

The aims of my research are to delineate the mechanisms through which the innate immune system acts to maintain tissue homeostasis in healthy individuals using both basic and translational approaches. An improved understanding of these immune pathways will lead to the identification of novel therapeutic targets for chronic human inflammatory diseases in which tissue homeostasis is dysregulated, such as IBD and asthma.

Biograpy

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I obtained a BSc (Hons) in Microbiology from the University of Manchester, during which I spent an industrial year working at the Mayo Clinic in the USA. Following this I undertook my PhD in the lab of Richard Grencis at the University of Manchester with a focus on immunity to helminth infections in the intestine. I later trained as a postdoc at the Humboldt University in Berlin with Susanne Hartmann where I further developed my expertise in mucosal immunology, before joining the laboratories of Gregory Sonnenberg and David Artis at the University of Pennsylvania (and later Weill Cornell Medical College, New York City) in 2012. In this position I worked in the rapidly developing field of Innate Lymphoid Cell (ILC) biology and performed translational studies that identified a novel role for ILCs in regulating intestinal inflammation in the context of Inflammatory Bowel Disease. At the start of 2016 I returned to the University of Manchester as a Wellcome Trust Sir Henry Dale fellow and established an independent research group.

Email: Matthew.hepworth@manchester.ac.uk

Phone: +44 (0)161 275 5247

People

Matthew Hepworth – People

Joshua Dow

People

Matthew Hepworth – People

Joshua Dow

Publications

  • Hepworth, M., Fung, T., Masur, S., Kelsen, J., McConnell, F., Dubrot, J., Withers, D., Hugues, S., Farrar, M., Reith, W., Eberl, G., Baldassano, R., Laufer, T., Elson, C. & Sonnenberg, G (2015). Immune tolerance. Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4⁺ T cells. Science, 348(6238), 1031-5. eScholarID:294238 | PMID:25908663 | DOI:10.1126/science.aaa4812
  • Hepworth, M. & Sonnenberg, G (2014). Regulation of the adaptive immune system by innate lymphoid cells. Curr Opin Immunol, 27, 75-82. eScholarID:294242 | PMID:24594491 | DOI:10.1016/j.coi.2014.01.013
  • Hepworth, M., Monticelli, L., Fung, T., Ziegler, C., Grunberg, S., Sinha, R., Mantegazza, A., Ma, H., Crawford, A., Angelosanto, J., Wherry, E., Koni, P., Bushman, F., Elson, C., Eberl, G., Artis, D. & Sonnenberg, G (2013). Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria. Nature, 498(7452), 113-7. eScholarID:294240 | PMID:23698371 | DOI:10.1038/nature12240
  • Hepworth, M., Daniłowicz-Luebert, E., Rausch, S., Metz, M., Klotz, C., Maurer, M. & Hartmann, S (2012). Mast cells orchestrate type 2 immunity to helminths through regulation of tissue-derived cytokines. Proc Natl Acad Sci U S A, 109(17), 6644-9. eScholarID:294244 | PMID:22493240 | DOI:10.1073/pnas.1112268109