Dr Gunnel Halldén

Dr Gunnel Halldén

PhD
Centre: Molecular Oncology
Reader in Cancer Gene Therapy
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QMUL Directory


The research in our team is focused on the development of novel treatment strategies to target prostate cancers and pancreatic cancers using genetically modified viruses that target, replicate and kill cancer cells (replication-selective oncolytic viruses) but leave normal cells unharmed.

Research Details

The recent first approval of an oncolytic herpes virus (T-Vec) by the EC and the FDA has demonstrated the feasibility and effectiveness of these biological agents. The focus in our team is on developing potent oncolytic adenoviral mutants that act in synergy with current anti-cancer therapeutics. The specific aims of the research are:

  • To construct highly tumour-specific and potent oncolytic viruses containing a combination of genetic changes - deletions, mutations, heterologous promoters and transgenes - for optimal efficacy in cancer tissue.
  • To determine cellular mechanisms for synergistic interactions of viral mutants with current therapeutics such as cytotoxic drugs and small molecule inhibitors.
  • To explore the efficacy of combinations of oncolytic viruses with non-toxic anti-cancer agents, for example phytochemicals.
  • To dissect the molecular signalling pathways that cause enhanced cell killing including apoptosis and autophagy pathways with the aim of identifying novel targets for development of improved therapeutics.
  • To develop model systems for pancreatic and prostate cancer that enable testing of oncolytic viruses ex vivo in cancer cell lines and primary tumour cells.

The overall goal of the team is to develop improved therapies for late stage, currently treatment-resistant cancers, by constructing potent tumour specific oncolytic viruses to be investigated and evaluated in combination with other cytotoxic therapies.

Profile

I joined the Barts Cancer Institute, in November 2004, as a Lecturer starting a Cancer Gene Therapy team, funded by the Flavell Bequest Programme in Prostate Cancer Gene Therapy. I completed my BSc at the University of Stockholm and Karolinska Institute, and my PhD at UC Berkeley in the USA. My post doctoral training was in cell and molecular biology at UC Berkeley, in oncolytic viruses at Onyx Pharmaceuticals (Richmond, CA, USA) and the Molecular Oncology Unit at Hammersmith Hospital in London.

In 2008 I was awarded my PGCAP (Postgraduate Certificate in Academic Practice) in teaching and learning from QMUL.

Funding

2016 - 2018 Barts and the London Charity "Identifying new therapeutic strategies for late-stage prostate cancer patients using a unique ex vivo culture model that mimics the tumour environment in situ"
£142,000
2015 - 2016 Pancreatic Cancer UK "Targeting αvβ6-integrin expressing pancreatic cancers with a mutant adenovirus for imaging and therapy."
£75,000

2013 - 2016

The Prostate Cancer Charity PhD project: "Develop novel therapies for advanced prostate cancers by dissecting deregulated cell survival"
£99,996
2013 - 2014 Pancreatic Cancer Research Fund Extended PhD project 
£28,000
2012 - 2014 Pancreatic Cancer Research Fund Postdoctoral project: "Improved virotherapy for intefrin-expressing pancreatic cancers"
£149,687
2010 - 2013 Pancreatic Cancer Research Fund PhD project: "Targeting pancreatic cancer with oncolytic virotherapy and cytotoxic drugs identification of cellular mechanism and biomarkers for treatment responses"
£116,940

Key Publications

Pantelidou C, Cherubini G, Lemoine NR, Halldén G. The E1B19K-deleted oncolytic adenovirus mutant AdΔ19K sensitizes pancreatic cancer cells to drug-induced DNA-damage by down-regulating Claspin and Mre11. Oncotarget. 2016. PMID: 26872382

Miranda E, Maya Pineda H, Öberg D, Cherubini G, Garate Z, Lemoine NR, Halldén G. (2012) Adenovirus-mediated sensitization to the cytotoxic drugs docetaxel and mitoxantrone is dependent on regulatory domains in the E1ACR1 gene-region. PLoS One. 2012. 23056370

Adam V, Ekblad M, Sweeney K, Müller H, Busch KH, Johnsen CT, Kang NR, Lemoine NR, Halldén G. (2012) Synergistic and Selective Cancer Cell Killing Mediated by the Oncolytic Adenoviral Mutant AdΔΔ and Dietary Phytochemicals in Prostate Cancer Models. Hum Gene Ther. 2012. 22788991

Öberg D, Yanover E, Adam V, Sweeney K, Costas C, Lemoine NR, Halldén G. Improved potency and selectivity of an oncolytic E1ACR2 and E1B19K deleted adenoviral mutant (AdΔΔ) in prostate and pancreatic cancers. Clin Cancer Res, 2010. PMID: 20068104


Further Publications

For additional publications, please click here.


The research in our team is focused on the development of novel treatment strategies to target prostate cancers and pancreatic cancers using genetically modified viruses that target, replicate and kill cancer cells (replication-selective oncolytic viruses) but leave normal cells unharmed.

External Activities

Teaching activities

  • Postgraduate tutor for the Centre of Molecular Oncology
  • Mentor for 1st and 2nd year Medical students at QMUL
  • Co-lead on ‘Introduction to Cancer Biology’ for first year Medical students
  • Lead on MSc module ‘Drug Development’
  • Lecturing on Gene therapy, oncolytic viruses and cancer biology for MSc and BSc students at QMUL, Imperial College and the Royal Veterinary College
  • Supervising several BSc students (from European and Chinese Universities, the Royal Veterinary College and QMUL) in their last year research projects.

External Activities

  • Editorial Board Member: Molecular Therapy and Molecular Therapy – Oncolytics
  • Research Grant Reviewer for funding bodies including, the European Commission, the British Medical research Council (MRC), the INSERM (France), the World wide Cancer Research Organisation, the Skolkovo Organisation (Russia), and the British Society for Gene and Cell Therapy (BSGCT) research bursary.
  • Referee of scientific journals including Molecular Therapy, Nature Review Urology, Molecular Oncology, Oncotarget, Cancer Research, Gene Therapy, Human Gene Therapy, EMBO, Advances in Virology, Journal of Virology.
  • Active member of professional organisations including the American Society for Cell and Gene Therapy (ASGCT), the European and British Societies for Cell and Gene Therapy (ESGCT and BSGCT), the American Association for Microbiology (ASM).

News

  • Invited Guest Lecturer on The Advanced Course in Clinical and Molecular Virology in Porto, Portugal (May 2016) to lecture on ‘Oncolytic viruses targeting prostate and pancreatic cancer.’
  • Oral presentation at the BSGCT in London (April 2016) of recent research ‘The AdΔΔ mutant enhances mitoxantrone-induced apoptosis and attenuates autophagy in prostate cancer.’
  • Publication in Oncotarget on virotherapy and immunotherapy in drug-resistant pancreatic cancer
  • Invited speaker at the ESGCT conference in Helsinki, Finland (October 2015) ‘The oncolytic adenovirus mutant AdΔ19K sensitizes pancreatic cancer cells to drug-induced DNA-damage by down-regulating Claspin and Mre11. ‘
  • Presented two posters at the 8th International Meeting on Replicating Oncolytic Virus Therapeutics (April, 2014), Oxford UK.  'Oncolysis is greatly enhanced by retargeting of replication-selective adenoviral mutants to avß6-integrin expressing cancers and 'Adenoviruses deleted in the anti-apoptotic E1B19K-gene synergise with DNA-damaging drugs through attenuation of DNA-damage repair responses and checkpoint activation'
  • Invited speaker at the 7th International Meeting on Replicating Oncolytic Virus Therapeutics (June 15-18, 2013), Québec City, Canada. Seminar on ‘The oncolytic mutant Ad∆∆ synergises with cytotoxic drugs through induction of apoptosis, attenuation of autophagy and aberrant mitosis in prostate and pancreatic cancer models’.
  • My work funded by Prostate Cancer UK
  • A video of my work funded by the Pancreatic Cancer Research Fund can be found here.

See other researchers working on:

Gene Therapy Genitourinary Cancer Pancreas Prostate Viruses
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