Dr Kathryn McIntosh

Teaching Fellow

Strathclyde Institute of Pharmacy and Biomedical Sciences

Contact

Personal statement

I am a research scientist and lecture in Pharmacology and cell signalling here in SIPBS. My research interests lie in the area of GPCRs, focussing on Proteinase activated receptors (PARs). In particular I am interested in the pharmacology of PAR2 and its pathophysiological role in inflammatory disease. Specifically investigating chronic inflammatory disorders such as rheumatoid arthritis and latterly the role of PAR2 in cancer, looking at prostate and breast cancer cell models. I have been working on novel small molecule modulators of PAR2 in collaboration with Dr Craig Jamieson from Pure and Applied Chemistry. Our group consists of 3 PhD students, working in different areas of cell Signalling, as part of the Cellular basis of disease group within SIPBS. I am co-head of the Research committee here in SIPBS and as such regularly sit on the Research and knowledge exchange management meetings. I am also part of the University wide research committee.

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Publications

A novel role for IL-1b in non-canonical NFkB signalling in U20S cells
Tinto Kirsty, McIntosh Kathryn, Cunningham Margaret Rose, Plevin Robin
19th World Congress of Basic & Clinical Pharmacology 2023 (2023)
TAK1 is an upstream MAP 3 K regulator of a novel non-canonical NFkB pathway stimulated by IL-1b
Farhan Mohammad, McIntosh Kathryn A, Cunningham Margaret R, Plevin Robin, Tinto Kirsty
British Journal of Pharmacology Vol 180, pp. 708-709 (2023)
https://doi.org/10.1111/bph.16110
IL-1β stimulates a novel, IKKα -dependent, NIK -independent activation of non-canonical NFκB signalling
McIntosh Kathryn, Khalaf Yousif H, Craig Rachel, West Christopher, McCulloch Ashley, Waghmare Ajay, Lawson Christopher, Chan Edmond YW, MacKay Simon, Paul Andrew, Plevin Robin
Cellular Signalling Vol 107 (2023)
https://doi.org/10.1016/j.cellsig.2023.110684
The development of proteinase-activated receptor-2 modulators and the challenges involved
McIntosh Kathryn A, Cunningham Margaret R, Bushell Trevor, Plevin Robin
Biochemical Society Transactions Vol 48, pp. 2525-2537 (2020)
https://doi.org/10.1042/BST20200191
Novel protective role for MAP kinase phosphatase 2 in inflammatory arthritis
Schroeder Juliane, Ross Kirsty, McIntosh Kathryn, Jabbar Shilan Khayrula Jabbar, Woods Stuart, Crowe Jenny, Patterson-Kane Janet C, Alexander James, Lawrence Catherine, Plevin Robin
RMD Open Vol 5, pp. e000711 (2019)
https://doi.org/10.1136/rmdopen-2018-000711
Inhibition of cytokine-mediated JNK signalling by purinergic P2Y11 receptors, a novel protective mechanism in endothelial cells
Ng Pei Y, McIntosh Kathryn A, Hargrave Gillian, Ho Ka H, Paul Andrew, Plevin Robin
Cellular Signalling Vol 51, pp. 59-71 (2018)
https://doi.org/10.1016/j.cellsig.2018.07.016

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Teaching

I was awarded my PG Cert in teaching, learning and assesment in 2016 where I also become a recognised fellow of the higher education academy.

I have since 2014 taught and more recently co-ordinated the PP904 compulsory PhD class on abstract writing, poster presentation and presentation skills. I was also actively involved in the organisation of the CPU summer school run here in SIPBS.

I am module co-ordinator and teach on both year 3 and year 4 Pharmacology semester One classes, I also coordinate and teach on the MSc Advanced Pharmacology module. I also coordinate year 2 Introduction to Immunology. 

I am teaching Pharmacology across years 2-4 and at Masters level and Immunology across years 2-3. I am actively involved in research with both Honours and Masters level students in the lab to complete wet lab projects.  I am also part of the BMS accreditation team and leading the redesign of the critical analysis projects at Masters level. I am currently involved with the redesign of the Introductory content for Immunology. 

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Research Interests

Current Collaborators: 

CXCL12-IKKa project = Professor Valerie Speirs (University of Aberdeen) and Dr Craig Jamieson (UoS)

PAR2-Osteoarthrits project = Professor Robin Plevin (UoS), Dr Anne Crilly (University of the West of Scotland), Dr Craig Jamieson (UoS) and Dr Zahra Rattray (UoS)

 

Professional Activities

Advanced Immunology course by university of Strathclyde, Glasgow
Recipient
6/2/2024
Beyond the Vaccine
Recipient
20/11/2023
British Pharmacological Society (Publisher)
Peer reviewer
31/7/2023
IUPHAR Education Satellite Meeting
Participant
2/7/2023
A novel role for IL-1b in non-canonical NFkB signalling in U2OS cells
Speaker
2/7/2023
19th World Congress of Basic & Clinical Pharmacology 2023
Participant
2/7/2023

More professional activities

Projects

Development and preclinical validation of novel PAR2 inhibitors for the treatment of Osteoarthritis
McIntosh, Kathryn (Principal Investigator) Crilly, Anne (Co-investigator) Jamieson, Craig (Co-investigator) Plevin, Robin (Co-investigator) Rattray, Zahra (Co-investigator)
01-Jan-2020 - 30-Jan-2022
Preventing the damaging effects of cancer chemotherapy and radiation treatment on human endothelial cells targeting the JNK pathway
Plevin, Robin (Principal Investigator) Boyd, Marie (Co-investigator) McIntosh, Kathryn (Co-investigator)
Preventing the damaging effects of cancer chemotherapy and radiation treatment on human endothelial cells targeting the JNK pathway
01-Jan-2019 - 31-Jan-2023
Development of novel PAR2 antagonists to treat inflammatory disease
McIntosh, Kathryn (Principal Investigator)
Based on the recently published PAR2 crystal structure, a novel series of PAR2 antagonists were developed - namely the AZ series. However these require further target validation and elucidation of there pharmacological properties, and from these novel derivatives will be developed.
05-Jan-2018 - 29-Jan-2025
Preclinical validation of novel PAR-2 inhibitors for the treatment of Osteoarthritis and Cancer
McIntosh, Kathryn (Research Co-investigator) Plevin, Robin (Principal Investigator)
Preclinical validation of novel PAR-2 inhibitors for the treatment of Osteoarthritis and Cancer.

Protease-activated Receptor 2 (PAR-2) is a member of a unique family of G-protein coupled receptors activated by serine protease cleavage of the N-terminus to generate a new tethered ligand. The distribution of this receptor, up-regulation by cytokines and activation by proteases, strongly suggests a role in inflammation. Indeed, we have established a key role for PAR-2 in chronic joint disease and the group are world leaders (Crilly et al., 2012; Ferrell et al., 2010; Ferrell et al., 2003; Kelso et al., 2006). Recently, we established for the first time a role for PAR-2 in osteoarthritis a condition affecting more than 4.4 million sufferers in the UK and a cost to society estimated at over £1B annually. Our current studies show that mice lacking the PAR-2 gene are protected from arthritis for up to a year, a breakthrough finding. Given the paucity of drugs for this disease our data highlights the clinical potential of PAR-2 antagonism. PAR-2 inhibition may also be of benefit in other conditions, for example in cancer, where recent studies have linked cancer progression to the inflammatory environment.
To date the translational aspect of PAR-2 biology has developed slowly due to the lack of potent and selective antagonists, although recently a number of moderately potent putative PAR-2 inhibitors have been identified. One of these, GB88, has also good oral availability. In our hands we find that GB88 functions as a partial agonist, making predictions as to its clinical value difficult. Therefore new and better prototype compounds are required to validate PAR-2 as a bonafide target in disease pathology. We have now identified two new lead compounds (141/2 and 143/1) which have a better antagonist profile (see figure 1 for 141/2), lacking the partial agonist activity of GB88. Our project is to determine if these drugs are effective in disease models, providing critical proof of concept data.


pFact ID (Internal Reference): 9932
RKES Reference (Internal Reference): 130814

SULSA (University Administered): £49,073.00, fEC% 49.00%

1/02/14 → 30/09/15

01-Jan-2014 - 30-Jan-2015

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Contact

Dr Kathryn McIntosh
Teaching Fellow
Strathclyde Institute of Pharmacy and Biomedical Sciences

Email: kathryn.a.mcintosh@strath.ac.uk
Tel: 548 2909