Dr Michelle Lockley

Dr Michelle Lockley

BSc, FRCP, PhD
Centre: Molecular Oncology
Reader in Medical Oncology/Honorary Consultant, Deputy Centre Lead
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I am a clinician scientist with a major research interest in ovarian cancer.

Our lab investigates oncolytic viral therapies and aims to improve their therapeutic benefit by manipulating the host immune response to these agents. We also aim to identify new therapies to treat chemotherapy-resistant ovarian cancer, which is currently an unmet clinical need.

 

Research Details

Chemotherapy Resistance

High grade serous cancer (HGSC) is the most common subtype of ovarian cancer. It is initially very responsive to platinum and taxane chemotherapy but more than 70% patients develop chemotherapy resistance and the disease becomes incurable.

Circumventing resistance is therefore a major unmet clinical need. The Lockley lab has created a panel of chemotherapy resistant HGSC cell lines and are using these to identify novel treatments for chemoresistant disease.

Oncolytic viruses

We aim to improve the utility of oncolytic viruses, whose clinical potential has so far been limited by inflammatory toxicity induced when they are administered systemically.

We showed for the first time that these inflammatory toxicities can be reduced by inhibition of β3 integrin, a cell surface signalling and adhesion protein, without compromising anticancer activity.

We now aim to further improve viral anti-cancer efficacy through combination with immune-modulatory therapies.

Tissue Collection

I set up and continue to lead the Barts Gynae Tissue Bank, This repository of tissue kindly donated by Barts patients is widely used by scientists at the BCI and elsewhere. It is the basis of the ERC funded CanBuild project lead by Prof Balkwill, which is creating innovative and accurate 3D models of the human omentum in high grade serous cancer.

I am Medical Adviser for this project

Clinical Trials

I am Principal Investigator for a number of clinical trials in gynaecological cancer, including a phase I/II trial of a novel oncolytic adenovirus, EnAd, which will open later this year.

Profile

Academic Positions

2015 – present: CRUK Advanced Clinician Scientist Fellowship
Senior Clinical Lecturer/Honorary Consultant in Medical Oncology, Deputy Centre Lead (2015)
Queen Mary University of London/Barts Health NHS Trust/UCLH

2011 – 2015: CRUK Clinician Scientist Fellowship
Queen Mary University of London/Barts Health NHS Trust

2009 – 2011: HEFCE Senior Clinical Lecturer/Hon. Cons. Medical Oncology
Queen Mary University of London/Barts Health NHS Trust

2008 – 2009: Clinical Lecturer and Honorary Specialist Registrar in Oncology
University of Cambridge

2003 – 2007: MRC Clinical Research Training Fellow
Queen Mary University of London

Education and Qualifications

2016: FRCP
2007: PhD (University of London)
2001: MRCP (Membership of the Royal College of Physicians), London
1997: MBBS (Bachelor of Medicine, Bachelor of Surgery), University College London
Distinctions in Medicine, Obstetrics/Gynaecology and Anatomy
1994: Honours Degree in Physiology, University College London, First Class

Funding

Recent Grants

  • 2016 - 2020: CR-UK - Advanced Clinician Scientist Fellowship: "New treatments for chemotherapy-resistant high grade serous ovarian cancer"
    £1.178m
  • 2015 - 2018: Barts and The London Charity - Strategic Research Grant: "Discovering new therapies for chemotherapy resistant high grade serous ovarian cancer"
    £197,545
  • 2011 - 2016: CR-UK - Clinician Scientist Fellowship
    £852,327
  • 2010 - 2011: Barts CR-UK Centre (BCC) - Development Fund
    £12,500
  • 2010 - 2011: Barts and The London Charity - Food for Thought Campaign
    £10,000

 

Key Publications

Browne AK, Tookman LA, Ingemarsdotter CK, Bouwman RD, Pirlo K, Wang Y, McNeish IA, Lockley M. Beta3 integrin inhibition reduces the inflammatory toxicities induced by oncolytic adenovirus without compromising anticancer activity. Cancer Res (2015). Accepted for publication May 2015

Böhm S, Faruqi A, Said I, Lockley M, Brockbank E, Jeyarajah A, Fitzpatrick A, Ennis D, Dowe T, Santos JL, Cook LS, Tinker AV, Le ND, Gilks CB, Singh N. Chemotherapy Response Score (CRS): Development and validation of a system to quantify histopathological response to neoadjuvant chemotherapy in high-grade serous tubo-ovarian carcinoma. J Clin Oncol. (2015). Accepted for publication Mar 2015

Ingemarsdotter CK, Tookman LA, Browne AK, Pirlo K, Cutts R, Chelela C, Khurrum K, Leung E, Dowson S, Webber L, Khan I, Ennis DP, Syed N, Crook TR, Brenton JD, Lockley M, McNeish IA. (2014) Paclitaxel resistance increases oncolytic adenovirus efficacy via upregulated CAR expression and dysfunctional cell cycle control. Mol Oncol. (2014) 25560085

Connell CM, Shibata A, Tookman LA, Flak MB, Pirlo KJ, Lockley M, Wheatley SP,  McNeish IA. Genomic DNA damage and ATR-Chk1 signalling determine oncolytic adenoviral efficacy in human ovarian cancer.  JCI (2011) 121(4): 1283-97. PMID: 21383502


Further Publications

For additional publications, please click here.


I am a clinician scientist with a major research interest in ovarian cancer.

Our lab investigates oncolytic viral therapies and aims to improve their therapeutic benefit by manipulating the host immune response to these agents. We also aim to identify new therapies to treat chemotherapy-resistant ovarian cancer, which is currently an unmet clinical need.

 

External Activities

  • NCRI Gynaecological Cancers Clinical Study Group
  • NCRI Ovarian Cancer Subgroup
  • London Cancer Gynaecology Pathway Board
  • Barts Cancer CAG Research Governance Committee
  • Barts Cancer Institute Teaching and Learning Committee
  • UCLP Academic Medical Oncology Training Lead
  • UCLP Medical Oncology Training Programme Management Committee
  • eCancer Medicine online journal Editorial Board

News

  • September 2015: Awarded a Cancer Research UK Clinician Scientist Fellowship
  • January 2015: Appointed Deputy Centre Lead for the Centre for Molecular Oncology
  • October 2014: Barts & The London Charity grant awareded (£200k)
  • August 2013: Co-applicant for a grant from Wellbeing Of Women to study endometrial cancer
  • June 2011: Awarded a Cancer Research UK Clinician Scientist Fellowship
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