James Hewitson
Lecturer in Biomedical Science

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Profile

Biography

James Hewitson is a Lecturer in Biomedical Science at the Centre for Immunology and Infection. He obtained his BSc in Biology and PhD in schistosome immunobiology from the Department of Biology at the University of York. From 2005, he did postdoctoral research in helminth immunology in the laboratory of Prof. Rick Maizels at the University of Edinburgh, and from 2014 with Dr. Dimitris Lagos working on non-coding RNA and inflammation. He began his current position at the University of York in May 2017.

Career

University of York: BSc in Biology 2001

University of York: PhD in Biology 2005

University of Edinburgh: Postdoctoral Fellow 2005-2013

University of York: Postdoctoral Fellow 2014-2017

University of York: Lecturer in Biomedical Sciences May 2017

Contact details

James Hewitson
Lecturer in Biomedical Science
Centre for Infection & Immunology

Tel: 01904 328576

Research

Overview

RESEARCH

Overview

Helminth infection (intestinal nematodes, schistosomes)

Skin and mucosal immunology

Vaccination

Immunomodulation

Non-coding RNA in immunity

More than 25% of the population of the world is infected with a helminth parasite, and the global burden of these diseases disproportionately afflicts those in Low-Middle Income Countries (LMIC). Helminth infections are predominantly thought of as “disablers” rather than killers, and disease-associated morbidity leads to a very high cost as measured by disability-adjusted life years (DALYs). This is particularly true for schistosomiasis (>200 million infected) and infection with intestinal nematodes (>1 billion infected). Additionally, helminth infection of livestock causes reduced yields and a significant economic cost for both LMIC and Western countries. Human disease is currently controlled through curative chemotherapy administered in Mass Drug Administration programs (MDA), and this has undoubtedly reduced disease in some regions. However, because people can rapidly become re-infected, and with the on-going concerns about the development of drug resistance, there is an urgent need to develop successful vaccines against these parasites.

Discoveries

Parasitic helminths act as long-lived foreign grafts, surviving within the mammalian host for years in the face of potential immune attack. This longevity has been attributed to the ability of the parasite to manipulate the host immune system, a process thought to be dependent upon worm secretions (“excretory/secretory” material or ES). Through proteomic techniques, we initially characterized ES material from the human parasite Brugia malayi, the causative agent of lymphatic filariasis(Hewitson et al 2008). We used this information to develop inhibitors of specific parasite molecules, finding them to act as a transmission-blocking therapeutics (Hewitson et al 2014). Next, we began investigating the intestinal nematode Heligmosomoides polygyrus, a chronic infection used as a model of human hookworms and veterinary nematodes. Here we found that parasite ES material constitutes a very good vaccine, and generates complete immunity against a challenge infection (Hewitson et al 2013). Investigation into the immunological mechanisms of protection revealed two essential protective components (1) high titer antibodies that neutralize parasite ES material, so allowing (2) coordinated myeloid cell attack of the larval parasite and worm expulsion (Hewitson et al 2015).

Current Projects

We are now interested in the following general questions

- How do myeloid cells such as macrophages mediate protective responses?

- And what are the host and parasite factors that regulate this?

- Can we target other parasites through their ES products?

- How does co-infection influence skin-stage immune responses?

- What is the role of non-coding RNA in type 2 immunity?

Research Group

We are a new lab and will be expanding over the next few months. If you are interested in joining please email me at james.hewitson@york.ac.uk.

Selected References

Hewitson JP et al The secretome of the filarial parasite, Brugia malayi: proteomic profile of adult excretory-secretory products. Mol Biochem Parasitol. 2008.

Hewitson JP et al The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo. PLoS Pathog. 2014.

Hewitson JP et al Secretion of protective antigens by tissue-stage nematode larvae revealed by proteomic analysis and vaccination-induced sterile immunity. PLoS Pathog. 2013.

Hewitson JP et al Concerted activity of IgG1 antibodies and IL-4/IL-25-dependent effector cells trap helminth larvae in the tissues following vaccination with defined secreted antigens, providing sterile immunity to challenge infection. PLoS Pathog. 2015.

 

 

 

 

 

Publications

Selected publications

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