Dr Sarah Martin
Research Interests
Dr Sarah Martin's main research themes are in Cancer Cell Biology and Cancer Genetics, as well as: Apoptosis; Cancer Cell Biology; Cell Signalling; Drug Resistance; Gynaecological Cancer; Lung; Cancer and Mesothelioma; Metabolism; Senior Researcher; Brain Tumours; Colorectal Cancer; Genomic Stability; DNA repair
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
2013-2016: Cancer Research UK Clinical Research Fellowship for Dr. Sukaina Rashid
Title: Targeting mitochondrial function as a therapeutic strategy for MLH1 deficient disease
2012-2015: Medical Research Council New Investigator Award, Total: £429,533
Title: Characterization and impact of novel regulators of mitochondrial DNA integrity on tumourigenesis
2012-2015: British Lung Foundation & the June Hancock Mesothelioma Research Fund, Total: £179,076
Co-PI: Dr. Peter Szlosarek
Title: Synthetic lethality in argenine auxotrophic malignant mesothelioma
2012-2015: Barts and the London Charity project grant, Total: £192,857
Title: Targeting MSH6 deficiency in temozolomide resistant glioblastomas
2012-2013: Cancer Research UK Clinician Bursary for Dr. Sukaina Rashid, Total: £14,500
Title: Targeting mitochondrial function as a therapeutic strategy for MLH1 deficient disease
2011-2014: Barts & the London Medical School PhD Studentship, Total: £60,000
Title: Using high-throughput screening to identify modulators of response to 5-fluorouracil
(5-FU) treatment in Mismatch Repair Deficient Cancer
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. 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. 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): 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. 20049735
Research Group
Mismatch repair and mitochondrial DNA repair group
- Delphine Guillotin - PhD student
- Dr. David Brierley - Postdoctoral research fellow
- Dr. Sukaina Rashid - Clinical research fellow
- Dr. Matthew Locke – Postdoctoral research fellow
- Gemma Bridge - Postdoctoral research fellow
External Activities
- Editorial Advisory Panel for the Biochemical Journal
- Member of The British Association for Cancer Research
- Member of the Biochemical Society
News
- Dr Sarah Martin wins Cancer Research UK's Future Leaders in Cancer Prize.
- Dr Sarah Martin awarded MRC New Investigator Award
