Projects per year
Personal profile
Research Statement
It has become increasingly clear that rather than being a single disease, cancer is a heterogeneous collection of diseases. It therefore follows that in order to diagnose and treat cancer effectively, strategies for patient selection must be combined with the development of molecularly targeted therapeutics so that patients can receive the drug or combination of drugs which is most appropriate for the treatment of their disease, at the appropriate time. This approach necessitates the involvement of multi-disciplinary teams of basic researchers and clinicians, working within an infrastructure which allows for effective knowledge transfer.
Working in close partnership with researchers from across the University and local hospitals, as well as with external researchers, our lab aims to identify new validated targets which have a clear path to patient selection and to develop strategies to modulate their function. Working closely with colleagues within the Centre (which includes the new Northern Ireland Molecular Pathology Lab and Biobank), a strong emphasis will be placed on the early development of biomarkers, both for patient selection, and for monitoring pharmacodynamic response.
The capabilities of the group include:
- Medicinal chemistry expertise in hit identification, hit to lead and lead optimisation
- Fragment screening (using a range of orthogonal biophysical techniques).
- Computer aided drug design
- Measurement and interpretation of Absorption, Distribution, Metabolism and Excretion (ADME) and physicochemical properties of molecules.
- State of the art compound storage and data management facilities
Research in our lab is currently focussed in the following areas:
- Discovery of inhibitors of ubiquitin specific proteases and other ligases involved in the ubiquitin-proteasome system,
- Identification of small molecule modulators of DNA damage response
- Developing new strategies for the disruption of protein-protein interactions, using fragment screening and by structure based design of constrained peptides
- Design and synthesis of new fragment screening libraries exploiting functional groups which are currently under-represented in organic synthesis
The multidisciplinary environment within the Centre for Cancer Research and Cell Biology, itself situated within easy reach of other research QUB faculties and Clinical Centres, offers an exciting opportunity for chemists, biologists, bioinformaticians, physicists, radiographers and clinicians to combine their expertise to facilitate the drug discovery process.
Achievements
Tim Harrison joined CCRCB in June 2013 having been appointed to the position of McClay Professor of Medicinal Chemistry. He obtained a first class BSc degree in chemistry from Nottingham University, and then stayed at Nottingham to complete a PhD in synthetic organic chemistry with Prof. G Pattenden, studying the application of new radical chemistry in organic synthesis. Tim then moved to the University of California at Irvine to undertake postdoctoral studies with Prof. L Overman aimed toward natural product synthesis using oxonium and iminium-ion rearrangements.
In 1991 Tim joining Merck Sharp and Dohme in Harlow, U.K. where he worked for 15 years, eventually rising to the position of Director, Medicinal Chemistry Department. During this time, Tim played a leading role in a number of Merck’s drug discovery research programmes, several of which led to clinical candidates. Tim was recipient of the 2004 Thomas Alva Edison Patent Award as part of the team which identified the marketed Substance P antagonist Emend®. In 2006, he joined Almac Sciences as Vice President, Research and Development, and during this time played a key role in setting up Almac Discovery, an oncology biotech company which was launched in 2008. He sits on several external boards and advisory groups, and is author or inventor on over 120 papers and patents.
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
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Collaborations and top research areas from the last five years
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R1300CNR: Future Medicines Institute
Scott, C. (PI), Bruce, I. (CoI), Burden, R. (CoI), Burrows, J. (CoI), Collins, B. (CoI), Harrison, T. (CoI), James, J. (CoI), Kennedy, R. (CoI), Lawler, M. (CoI), Longley, D. (CoI), Maguire, S. (CoI), Malinova, D. (CoI), Maule, A. (CoI), McCloskey, K. (CoI), McDade, S. (CoI), Salto-Tellez, M. (CoI), Savage, K. (CoI), Stitt, A. (CoI) & Williams, R. (CoI)
15/10/2024 → …
Project: Research
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R1049CNR: The cell death regulator FLIP: evaluation of novel inhibitors in colorectal cancer
Longley, D. (PI), Dunne, P. (CoI), Harrison, T. (CoI), Kerr, E. (CoI) & McDade, S. (CoI)
29/03/2019 → …
Project: Research
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R1133CNR: Targeting FLIP to overcome resistance to targeted agents in non-small cell lung cancer
Longley, D. (PI) & Harrison, T. (CoI)
10/01/2020 → 30/06/2022
Project: Research
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R3511CNR: Establishment of an Integrated Almac-QUB Drug Discovery Unit at CCRCB
Harrison, T. (PI), Harkin, P. (CoI), Johnston, P. (CoI), Kennedy, R. (CoI), Longley, D. (CoI), Mullan, P. (CoI), Prise, K. (CoI), Salto-Tellez, M. (CoI), Waugh, D. (CoI), Williams, R. (CoI) & Wilson, R. (CoI)
01/08/2012 → 30/04/2016
Project: Research
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USP7 inhibitors suppress tumour neoangiogenesis and promote synergy with immune checkpoint inhibitors by downregulating fibroblast VEGF
Jurisic, A., Sung, P.-J., Wappett, M., Daubriac, J., Lobb, I. T., Kung, W.-W., Crawford, N., Page, N., Cassidy, E., Feutren-Burton, S., Rountree, J. S. S., Helm, M. D., O'Dowd, C. R., Kennedy, R. D., Gavory, G., Cranston, A. N., Longley, D. B., Jacq, X. & Harrison, T., 11 Apr 2024, In: Clinical and Translational Medicine. 14, 4, 22 p., e1648.Research output: Contribution to journal › Article › peer-review
Open AccessFile28 Downloads (Pure) -
Identification and development of a subtype-selective allosteric AKT inhibitor suitable for clinical development
Page, N., Wappett, M., O'Dowd, C. R., O'Rourke, M., Gavory, G., Zhang, L., Rountree, J. S. S., Jordan, L., Barker, O., Gibson, H., Boyd, C., Feutren-Burton, S., McLean, E., Trevitt, G. & Harrison, T., 20 Sept 2022, (Early online date) In: Scientific Reports. 12, 14 p., 15715.Research output: Contribution to journal › Article › peer-review
Open AccessFile4 Citations (Scopus)104 Downloads (Pure) -
A revised model of TRAIL-R2 DISC assembly explains how FLIP(L) can inhibit or promote apoptosis
Humphreys, L. M., Fox, J. P., Higgins, C. A., Majkut, J., Sessler, T., McLaughlin, K., McCann, C., Roberts, J. Z., Crawford, N. T., McDade, S. S., Scott, C. J., Harrison, T. & Longley, D. B., 31 Jan 2020, (Early online date) In: EMBO Reports. 21, e49254.Research output: Contribution to journal › Article › peer-review
Open AccessFile39 Citations (Scopus)203 Downloads (Pure) -
RALB GTPase: a critical regulator of DR5 expression and TRAIL sensitivity in KRAS mutant colorectal cancer
Khawaja, H., Campbell, A., Roberts, J. Z., Javadi, A., O’Reilly, P., McArt, D., Allen, W. L., Majkut, J., Rehm, M., Bardelli, A., Di Nicolantonio, F., Scott, C. J., Kennedy, R., Vitale, N., Harrison, T., Sansom, O. J., Longley, D. B., Evergren, E. & Van Schaeybroeck, S., 29 Oct 2020, (Early online date) In: Cell death and disease. 11, 10, 18 p., 930.Research output: Contribution to journal › Article › peer-review
Open AccessFile9 Citations (Scopus)104 Downloads (Pure) -
Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial
Inhaled Interferon Beta COVID-19 Study Group, 12 Nov 2020, In: The Lancet Respiratory Medicine. 9, 2, p. 196-206 11 p.Research output: Contribution to journal › Article › peer-review
333 Citations (Scopus)