Dr Kathryn McIntosh

Teaching Fellow

Strathclyde Institute of Pharmacy and Biomedical Sciences

Contact

Personal statement

I am a Immuno-pharmacology lecturer in SIPBS teaching actively across both disciplines. I am also the year 4 BMS coordinator. My research interests lie in the role of PAR2 in chronic inflammation and the role of NFkB within breast cancer associated fibroblasts. My research entails in vitro cellular studies in signalling, trafficking and drug design. 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. I also evaluate the role of CXCL12 and the NFkB pathway in the tumour microenvironment, looking specifically at cancer-associated fibroblasts. . I have been working on novel small molecule modulators of PAR2 in collaboration with Dr Craig Jamieson from Pure and Applied Chemistry. I collaborate with Professor Valerie Speirs from the University of Aberdeen and with Dr Anne Crilly from the University of the West of Scotland. 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 was previously co-head of the Research committee here in SIPBS and as such sat on the Research and knowledge exchange management meetings. I am also part of the University wide research committee.

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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 = Dr Anne Crilly (University of the West of Scotland), and Dr Craig Jamieson (UoS).

IKK-alpha signalling project = Prof Robin Plevin (UoS). 

 

Professional Activities

Frontiers in Immunology (Journal)
Peer reviewer
5/7/2024
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
A novel role for IL-1b in non-canonical NFkB signalling in U2OS cells
Speaker
2/7/2023
IUPHAR Education Satellite Meeting
Participant
2/7/2023

More professional activities

Projects

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-Feb-2023 - 29-Aug-2027
Evaluation of protease activated receptor 2 (PAR2) as a novel therapeutic target for chronic obstructive pulmonary disease (COPD)
Crilly, Anne (Principal Investigator) McIntosh, Kathryn (Academic)
Chronic obstructive pulmonary disease (COPD) is a progressive and highly debilitating lung condition now reported as being the third leading cause of death worldwide.The disease has no cure and is characterised by the presence of chronic bronchitis and emphysema.
Protease activated receptor 2 (PAR2) is a G-protein coupled receptor which has been shown to have a role in inflammatory disease pathology. The receptor has a unique mode of activation involving the cleavage of the N-terminal by specific serine proteases to reveal a tethered ligand which binds to extracellular loop two of the receptor causing cell signalling. Once activated, PAR2 will regulate the secretion of pro-inflammatory mediators, such as interleukin 6 (IL-6) and IL-8. While the role of PAR2 in COPD pathogenesis has been relatively underexplored, preliminary studies from our group have shown the receptor to be expressed in human bronchial epithelial cells (HBEC) from normal and COPD (or diseased) lung (DHBEC). The COPD lung is a rich source of proteases, with many of the serine proteases present, such as mast cell tryptase, neutrophil elastase and matriptase able to cleave PAR2, potentially driving inflammation. Using normal HBEC and the PAR2 activating protease, matriptase, we have generated an in vitro model reflective of the COPD lung environment. We have shown increased secretion of the inflammatory cytokines, IL-6 and IL-8, with increasing concentrations of matriptase (Figure 1), suggesting a role for PAR2 in this process. In addition to driving inflammation, PAR2 has also been reported as being able to ‘crosstalk’ with innate pathogen sensing receptors, namely toll-like receptor (TLR) 2, 3 and 4. COPD patients are susceptible to both viral and bacterial infection, with non-typeable Haemophilus Influenzae and Streptococcus pneumoniae most commonly reported and sensed via TLR2/3 and TLR4 respectively (expressed on lung epithelial cells). We hypothesise that a novel molecular axis linking PAR2 / inflammation and infection exists in bronchial epithelial cells and that PAR2 targeted treatment may be an attractive therapeutic approach in reducing COPD inflammation linked to proteases and infection
17-Oct-2022 - 31-Oct-2025
TAK-1 inhibition prevents cytokine-mediated CXCL12 production in a bone cancer cell line
McIntosh, Kathryn (CoPI)
01-Apr-2021 - 31-Oct-2024
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-Apr-2020 - 30-Sep-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-Apr-2019 - 31-Aug-2023
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-Feb-2014 - 30-Sep-2015

More projects

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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