Dr Kathryn McIntosh

Publications

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

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)

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

More publications

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. 

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

19th World Congress of Basic & Clinical Pharmacology 2023

Participant

2/7/2023

A novel role for IL-1b in non-canonical NFkB signalling in U2OS cells

Speaker

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

More projects