Dr Kathryn McIntosh
Teaching Fellow
Strathclyde Institute of Pharmacy and Biomedical Sciences
Prize And Awards
- VITAE International Research award
- Recipient
- 10/11/2021
- Fellow of the Higher Education Academy
- Recipient
- 10/10/2016
- Court Medal
- Recipient
- 25/6/2003
Publications
- Design and synthesis of novel aminoindazole-pyrrolo[2,3-b]pyridine inhibitors of IKKα that selectively perturb cellular non-canonical NF-κB signalling
- Riley Christopher, Ammar Usama, Alsfouk Aisha, Anthony Nahoum G, Baiget Jessica, Berretta Giacomo, Breen David, Huggan Judith, Lawson Christopher, McIntosh Kathryn, Plevin Robin, Suckling Colin J, Young Louise C, Paul Andrew, Mackay Simon P
- Molecules Vol 29 (2024)
- https://doi.org/10.3390/molecules29153515
- Proteinase activated receptor 2 : a novel therapeutic drug target
- Lozon Yosra, McIntosh Kathryn, Plevin Robin
- 2nd AUU Health and biomedical postgraduate Symposium (2024)
- Advanced Immunology by the University of Strathclyde, Glasgow
- McIntosh Kathryn
- (2024)
- Beyond the Vaccine
- McIntosh Kathryn
- (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
- 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)
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 = 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
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
Contact
Dr
Kathryn
McIntosh
Teaching Fellow
Strathclyde Institute of Pharmacy and Biomedical Sciences
Email: kathryn.a.mcintosh@strath.ac.uk
Tel: 548 2909