Professor William Harnett

Strathclyde Institute of Pharmacy and Biomedical Sciences

Personal statement

I joined the Department of Immunology at Strathclyde University as a lecturer in 1991 and was appointed Professor of Molecular Immunology in 2002. Immunology was one of five University departments, which merged to form Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS) in 2006. I acted as Director of Research in SIPBS from August 2009 until the end of 2013 and was previously Head of The immunology Department during the academic year, 2005-6.

My research interests lie in elucidating the molecular mechanisms by which parasitic worms modulate the host immune system. A particular focus is on ES-62, an anti-inflammatory molecule secreted by the filarial nematode Acanthocheilonema viteae, which we are currently exploiting with a view to developing novel drugs for allergic and autoimmune diseases. This interest in immunology and parasitology also extends to my areas of teaching.

Publications

Synthetic small molecule analogues of the immunomodulatory Acanthocheilonema viteae product ES-62 promote metabolic homeostasis during obesity in a mouse model
Lumb Felicity E, Crowe Jenny, Doonan James, Suckling Colin J, Selman Colin, Harnett Margaret M, Harnett William
Molecular and Biochemical Parasitology Vol 234 (2019)
https://doi.org/10.1016/j.molbiopara.2019.111232
Site-specific glycoproteomic characterization of ES-62 : the major secreted product of the parasitic worm Acanthocheilonema viteae
North Simon J, Botchway Kwamina, Doonan James, Lumb Felicity E, Dell Anne, Harnett William, Haslam Stuart M
Glycobiology Vol 29, pp. 562-571 (2019)
https://doi.org/10.1093/glycob/cwz035
The parasitic worm product ES-62 normalises the gut microbiota bone marrow axis in inflammatory arthritis
Doonan James, Tarafdar Anuradha, Pineda Miguel A, Lumb Felicity E, Crowe Jenny, Khan Aneesah M, Hoskisson Paul A, Harnett Margaret M, Harnett William
Nature Communications Vol 10 (2019)
https://doi.org/10.1038/s41467-019-09361-0
Failure of the anti-inflammatory parasitic worm product ES-62 to provide protection in mouse models of type I diabetes, multiple sclerosis, and inflammatory bowel disease
Doonan James, Thomas David, Wong Michelle H, Ramage Hazel J, Al-Riyami Lamyaa, Lumb Felicity E, Bell Kara S, Fairlie-Clarke Karen J, Suckling Colin J, Michelsen Kathrin S, Jiang Hui-Rong, Cooke Anne, Harnett Margaret M, Harnett William
Molecules Vol 23 (2018)
https://doi.org/10.3390/molecules23102669
Synthetic analogues of the parasitic worm product ES-62 reduce disease development in in vivo models of lung fibrosis
Suckling Colin J, Mukherjee Sambuddho, Khalaf Abedawn I, Narayan Ashwini, Scott Fraser J, Khare Sonal, Dhakshinamoorthy Saravanakumar, Harnett Margaret M, Harnett William
Acta Tropica Vol 185, pp. 212-218 (2018)
https://doi.org/10.1016/j.actatropica.2018.05.015
Protection against arthritis by the parasitic worm product ES-62, and its drug-like small molecule analogues, is associated with inhibition of osteoclastogenesis
Doonan James, Lumb Felicity E, Pineda Miguel A, Tarafdar Anuradha, Crowe Jenny, Khan Aneesah M, Suckling Colin J, Harnett Margaret M, Harnett William
Frontiers in Immunology Vol 9 (2018)
https://doi.org/10.3389/fimmu.2018.01016

more publications

Professional activities

Molecular and Cellular Biology of Helminth Parasites IX
Speaker
30/8/2015
Molecular and Cellular Biology of Helminth Parasites IX
Chair
30/8/2015
The parasitic worm product ES-62: a starting point for novel anti-inflammatory drug development
Invited speaker
25/8/2015
Infection and Immunity (Journal)
Editorial board member
1/1/2015
International Filariasis Meeting
Invited speaker
26/9/2014
International Filariasis Meeting
Chair
26/9/2014

more professional activities

Projects

Do Excretory Secretory protein 62 (ES-62) small molecule analogues prevent blood brain barrier breakdown after experimental stroke?
McKittrick, Craig Martin (Research Co-investigator) Carswell, Hilary (Principal Investigator) Harnett, William (Principal Investigator)
01-Jan-2017 - 30-Jan-2017
Can studying the mechanism of action of the parasitic worm-derived immunomodulator ES-62, inform on how to slow ageing and improve healthspan?
Harnett, William (Principal Investigator)
"The introduction of vaccines and drugs to control disease, in combination with greater access to food and improved sanitation, means that people are now living much longer. Currently this increase is staggering, equating to an extra 2.5 years of life per decade. However, improved life expectancy itself amounts to a huge new problem, in that it is not being accompanied by a similar increase in health and wellbeing. This reflects both that like a mechanical machine such as a car engine, the ageing process is naturally associated with a loss of function of its systems due to wear and tear, but also that improved wealth has resulted in a modern Western life-style, incorporating a high fat diet (HFD) that contributes to age-associated ailments such as type-2 diabetes (T2D), stroke and heart disease. This impact of increased lifespan presenting with associated ill-health has enormous socio-economic implications due to its increasingly global scale, arguing for a need to better understand the process of ageing in the context of health.

Approximately one quarter of the world's population is infected with parasitic worms. Of interest, several recent reports indicate that such infections offer protection against development of conditions such as obesity, cardiovascular disease and T2D in mouse models and that similar protection may also be seen in humans. We have been studying one individual parasitic worm component - ES-62, isolated from the secretory products of the filarial nematode, Acanthocheilonema viteae, and consistent with these studies, ES-62 is highly effective in reducing the cardiovascular disease that arises in a highly susceptible strain of mouse, particularly in response to a high fat diet. Moreover, we have some preliminary data showing that ES-62 may offer some protection against development of the obesity that is associated with development of T2D.

Our studies to date with ES-62 also show it to be effective in inhibiting the development of disease in mouse models of allergy, rheumatoid arthritis and systemic lupus erythematosus. What all of these diseases have in common with cardiovascular disease and T2D is the increasing realization that they are associated with unwanted inflammation. This immediately offers an explanation for ES-62's protective effects, as the parasitic worm-derived molecule possesses a range of anti-inflammatory properties. Furthermore, as ageing is also now being considered as a biological problem in the setting of chronic low-grade inflammation, this raises the possibility of investigating the effect of ES-62 on the ageing process and late-life health and well being (healthspan). Thus, we specifically plan to determine whether ES-62 can slow ageing and improve healthspan using a paradigm where mice will be fed on a high fat diet +/- ES-62. We will use this model to assess the effect of ES-62 treatment on ageing in the context of promotion of gene signatures and signalling pathways known to be associated with ageing/inflammation versus those associated with longevity and healthspan.

In addition to enabling us to establish whether ES-62's anti-inflammatory properties are impacting on the ageing process at the molecular level as predicted, this strategy might allow us to validate novel biomarkers for ageing and even potential sites of therapeutic intervention. With respect to the latter, we have produced synthetic drug-like small molecule analogues (SMAs) of ES-62 during our work on the allergy and autoimmunity models, with a view to using these as a starting point in novel drug development for these conditions. Thus, although the current application is designed to increase understanding of the biology of ageing rather than drug development, we will conduct a small trial with one of these SMAs towards the final year of the project with a view to submitting future grant applications for impact funding for their development as potential therapies."
01-Jan-2016 - 31-Jan-2019
MIMIC - Do parasitic worms and their secreted immunomudulators protect against musculosketal disease by impacting on the host microbiome?
Harnett, William (Principal Investigator) Hoskisson, Paul (Co-investigator)
01-Jan-2015 - 30-Jan-2018
Using C. elegans to produce proteins from parasitic nematodes for research and therapeutic use
Harnett, William (Principal Investigator)
01-Jan-2014 - 30-Jan-2014
BBSRC Doctoral Training Grant (DTG) | Lumb, Felicity Elspeth
Harnett, William (Principal Investigator) Rotondo, Dino (Co-investigator) Lumb, Felicity Elspeth (Research Co-investigator)
01-Jan-2011 - 23-Jan-2016
Capacity Building Award in Integretive Mammalian Biology: A joint initiative from Glasgow University and Strathclyde University | Allan, Debbie
Jiang, Hui-Rong (Principal Investigator) Harnett, William (Co-investigator) Allan, Debbie (Research Co-investigator)
01-Jan-2010 - 23-Jan-2015

more projects

Address

Strathclyde Institute of Pharmacy and Biomedical Sciences
Hamnett Wing

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