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Personal profile

Personal Statement

Our group investigates the primary brain tumour glioblastoma (GBM), one of the most aggressive and incurable tumours in adults.  Treatment comprises surgery, radiation, and chemotherapy (temozolomide). Even with this aggressive therapy, tumours inevitably recur, conferring a life expectancy of approximately one year. Intensive research using conventional preclinical models, such as cells are grown in two-dimensional conditions (plastic dishes) or in three-dimensional models devoid of extracellular matrix or scaffolding support such as neurospheres, have identified multiple molecular targeted agents which have all failed in the clinic. Failure in the clinical translation of these agents imply that the conventional preclinical models used are not representative of GBM or its response to treatment. To elicit improved therapies for GBM patients and improve the poor survival rates, research in our group has focused in the development of appropriate models that better recapitulate the GBM microenvironment and evaluate how these cells respond to treatment.

 

Using a three-dimensional GBM model developed in our laboratory, that recapitulates key clinical features including cell morphology, migration, and clinical response to molecular targeted therapies, we have identified several molecular targets that induce radiation sensitivity as well as radiation protection.  We are currently investigating the mechanisms involved in these responses, in order to identify better treatments with clinical efficacy. 

Personal Statement

My research is highly collaborative and multidisciplinary with ongoing projects invested in understanding treatment response and resistance to therapy of glioblastoma (GBM) and ovarian carcinoma with the aim to identifying novel targets for the development of new therapeutic strategies. Investigations include the development of better preclinical models (three-dimensional in vitro models and in vivo), understanding mechanisms of standard of care treatment resistance and identification of novel targets with cytotoxic and/or radiosensitising activities, understanding cholesterol regulation of glioblastoma growth and treatment resistance, and evaluating novel DNA damage response inhibitors chemically engineered for improved brain-penetrance. I have actively developed a research network integrating expertise from clinicians, cancer scientists, physicists, chemists and radiobiologists that complement my current research goals.  Approaches used in my research include cellular imaging of cholesterol using Raman Spectroscopy and Time-of-Flight Single Ion Mass Spectrometry (ToF-SIMS) imaging techniques, in vivo evaluation of orthotopic tumours using Magnetic Resonance imaging (MRI), in vitro and in vivo irradiation with conventional X-Ray and novel plasma-accelerated Very High Energy Electron (VHEE) technologies and three-dimensional preclinical models.

Current University of Strathclyde collaborators (with collaborating project) include:

  • Dr Marie Boyd (SIPBS)
  • Dr Trevor Bushell (SIPBS)
  • Professor Duncan Graham (PAC)  

External collaborators include:

  • Professor Anthony Chalmers, University of Glasgow 
  • Dr Ross Carruthers, University of Glasgow 
  • Professor Hing Leung, Beatson Institute for Cancer Research 
  • Dr David Lewis, Beatson Institute for Cancer Research 
  • Dr Ola Rominiyi, University of Sheffield 
  • Dr Spencer Collis, University of Sheffield 
  • Dr Lucy Stead, University of Leeds (https://gliomodel.org.uk/)
  • Dr Adam McMahon, University of Manchester 
  • Dr Gerben Borst

Industrial collaborators include:

  • Dr Bob Boyle, Sentinel Oncology - brain-penetrant targeted molecules

I am a member of GlioModel (https://gliomodel.org.uk/), a collaboration of neuro-oncology research groups from 8 participating UK institutions, each housing one or more glioblastoma (GBM) preclinical models that span a range of  in vitro through ex vivo to in vivo experimental systems.  The aim of this group is to show how functional assessment of candidate pathogenic molecules or pathways across multiple models can be used to expedite preclinical target validation and give more in depth insight into mechanisms underpinning malignant phenotypes.  In this context models refers not just to specific cell lines but also the mode/environment in which cells are cultured or maintained.

I am also a member of the CRUK RadNet Glasgow community, and the RadNet drug-radiation combinations working group led by Prof. Chalmers (Glasgow) and Prof Williams (Manchester). Support from internal and external collaborators resulted in three small research grants funding pilot studies (two from Tenovus Scotland, and from RadNet Glasgow) investigating cholesterol role in radiation treatment response and developng novel 3D GBM-astrocyte hetero-cellular models.

Finally, I am a member of the National Cancer Research Institute Early Career Research Forum (NCRI ECRF), committed to influence national policy on cancer research Participation in meetings and networking events.

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):

  • SDG 3 - Good Health and Well-being

Keywords

  • Three-dimensional
  • cancer
  • radiation
  • high-throughput
  • organoids
  • scaffolds
  • glioblastoma
  • ovarian cancer
  • DNA damage and repair

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