Dr Sarah Martin

Dr Sarah Martin

PhD
Centre: Molecular Oncology
Senior Lecturer, Deputy Centre Lead
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Our research is based on exploiting DNA repair defects in cancer for the identification of new personalised therapies. We use compound and siRNA screening to identify new therapeutics for tumours based on their specific DNA repair status

 

Research Details

Our research group is involved in investigating nuclear and mitochondrial DNA repair as a therapeutic target in cancer. In particular, we have focused on the DNA mismatch repair (MMR) pathway, the system for recognising and repairing mistakes in DNA replication and so preventing genetic mutations.

MMR deficiency results in an increased predisposition to cancer, in particular colorectal and endometrial. We have carried out high-throughput screening of small interfering RNA (siRNA) and compounds and identified DNA polymerases, POLB & POLG, and the mitochondrial kinase PINK1 as novel targets for the treatment of MMR deficient disease.

We have also identified the drug Methotrexate as a selective, cytotoxic agent for cancers that are deficient in the mismatch repair gene, MSH2. These findings have led to a Phase 2 clinical trial in patients with metastatic colorectal cancer.

We are also investigating the role of mitochondrial DNA repair in cancer and whether this can be targeted as a therapeutic strategy.

Profile

I studied a BSc (Hons) in Microbiology at the National University of Ireland, Galway and completed my PhD in molecular biology from the same University in 2003. During my PhD, I studied the gene expression profiles of the hepatic and ocular tissues of the Atlantic salmon with Dr. Richard Powell.

I then moved to a postdoctoral position in the Mount Sinai School of Medicine in New York to join Dr. Toru Ouchi’s group, where I investigated the role of BRCA1 and its functional binding partners, specifically investigating the regulation of caspase-3 activation by BRCA1 phosphorylation. I was awarded a postdoctoral fellowship from the New York State Health Research Science Board.

In 2006, I joined Prof. Alan Ashworth’s group in the Breakthrough Breast Cancer Research Centre in the Institute of Cancer Research, London. Here, I carried out high-throughput RNAi and compound screens to indentify synthetic lethal interactions with deficiency in the DNA mismatch repair pathway.

I joined Barts Cancer Institute as a principal investigator in September 2010. My research group is focused on DNA mismatch repair deficiency and identifying new ways of treating cancer by targeting defects in nuclear and mitochondrial DNA repair. I was awarded the 2011 CRUK Future Leader in Cancer Research Prize.

Funding

2014-2017

Bowel & Cancer Research

PhD Studentship: "Targeting APC loss in colorectal cancer"
£74,916

2014-2017

Wellbeing of Women

Project Grant: “Targeting Mismatch repair deficiency in Endometrial Cancer”
£179,665

2012-2015

Medical Research Council

Characterization and impact of novel regulators of mitochondrial DNA integrity on tumourigenesis
£416,652

2012-2015

Cancer Research UK

Clinical Research Fellowship: “Targeting mitochondrial function as a therapeutic strategy for MLH1 deficient cancer”
£14,500

2012-2015

British Lung Foundation

“Targeting loss of ASS1 in malignant pleural mesothelioma” (Dr Peter Szlosarek co-investigator)
£123,356

2012

June Hancock Mesothelioma Research Fund

“Synthetic lethality in arginine auxotrophic malignant mesothelioma”
£53,945

2012

The Federation of Khoja of Shia Ithna-Asheri Jamaats of Africa

Salary Support
£67,679

2011-2014

Barts And The London Medical School

PhD Studentship: “Using high-throughput screening to identify modulators of response to 5-fluorouracil (5-FU) treatment in Mismatch  Repair Deficient Cancer”
£60,000

2011-2014

Barts And The London Charity

Project Grant: “Targeting MSH6 deficiency in temozolomide-resistant glioblastoma”
£ 192,857

Key Publications

Parallel High Throughput RNA interference Screens Identify PINK1 as a Potential Therapeutic Target for the Treatment of DNA Mismatch Repair Deficient Cancers. Martin S.A, Hewish M, Sims D, Lord C.J & Ashworth A. (2011) Cancer Research. PMID: 21242281

DNA Polymerases as Potential Therapeutic Targets for Cancers Deficient in the DNA Mismatch Repair Proteins, MSH2 or MLH1. Martin S.A, McCabe N, Mullarkey M, Cummins R, Burgess D.J, Kay E, Lord C.J & Ashworth A.  (2010) Cancer Cell. 17(3): 235-48. PMID: 20227038

Methotrexate induces Oxidative DNA Damage and is Selectively Lethal to Cells with Defects in the DNA Mismatch Repair Gene MSH2. Martin S.A, McCarthy A, Barber L.J, Burgess D.J, Lord C.J & Ashworth A. (2009).  EMBO Mol. Med. 1(6-7): PMID: 323-337. 20049736

Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors. Mendes-Pereira AM, Martin SA, Brough R, McCarthy A, Taylor JR, Kim JS, Waldman T, Lord CJ, Ashworth A. (2009) EMBO Mol Med. 1(6-7): 315-22. PMID: 20049735



Our research is based on exploiting DNA repair defects in cancer for the identification of new personalised therapies. We use compound and siRNA screening to identify new therapeutics for tumours based on their specific DNA repair status

 

External Activities

  • Editorial Advisory Panel for the Biochemical Journal
  • Member of The British Association for Cancer Research
  • Member of the  Biochemical Society

News

  • January 2015: Made Deputy Centre Lead for Molecular Oncology
  • January 2015: Wellbeing of Women endometrial cancer project covered by Mail Online
  • October 2013: Commented on our mesothelioma research for Stoptober
  • August 2013: Wellbeing of Women grant awarded for endometrial cancer research projects
  • August 2012: MRC and British Lung Foundation grants awarded to study mitochondria and mesothelioma.
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