• Room 03.021 - H.S.B

    United Kingdom

20112020

Research output per year

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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.

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Projects

Research Output

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, In : EMBO Reports. e49254.

Research output: Contribution to journalArticle

Open Access
File
  • 28 Downloads (Pure)

    Identification and SAR exploration of a novel series of Legumain inhibitors

    Eddie, S. L., Gregson, A., Graham, E., Burton, S., Harrison, T., Burden, R., Scott, C. J., Mullan, P. B. & Williams, R., 15 Jun 2019, In : Bioorganic & Medicinal Chemistry Letters. 29, 12, p. 1546-1548 3 p.

    Research output: Contribution to journalArticle

  • 32 Citations (Scopus)

    Identification and Structure-Guided Development of Pyrimidinone Based USP7 Inhibitors

    O'Dowd, C., Helm, M., rountree, S., Flasz, J. T., Arkoudis, E., miel, H., hewitt, P., jordan, L., barker, O., hughes, C., rozycka, E., cassidy, E., mcclelland, K., odrzywol, E., page, N., fuetren-burton, S., Dvorkin, S., gavory, G. & Harrison, T., 21 Feb 2018, In : ACS MEDICINAL CHEMISTRY LETTERS. 9, 3, p. 238-243

    Research output: Contribution to journalArticle

    Open Access
    File
  • 11 Citations (Scopus)
    154 Downloads (Pure)

    Thesis

    Molecular Biology of AKT Inhibition in Gastro-oesophageal Adenocarcinoma

    Author: Cairns, L., Jul 2019

    Supervisor: Turkington, R. (Supervisor), Kennedy, R. (Supervisor) & Harrison, T. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy