Dr Sarah Martin

PhD
Reader; Director of Graduate Studies for Research (BCI)
Deputy Centre Lead, Group Leader
Research Focus

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.

Key Publications

Drug-Repositioning Screens Identify Triamterene as a Selective Drug for the Treatment of DNA Mismatch Repair Deficient Cells. Clin Cancer Res (2017) 23(11):2880-2890. PMID: 27913567

Inhibition of the Polyamine Synthesis Pathway Is Synthetically Lethal with Loss of Argininosuccinate Synthase 1. Cell Rep (2016) 16(6): 1604-1613. PMID: PMC4978703

Parallel High Throughput RNA interference Screens Identify PINK1 as a Potential Therapeutic Target for the Treatment of DNA Mismatch Repair Deficient Cancers. Cancer Res (2011) 71(5):1836-48. PMID: 21242281

DNA Polymerases as Potential Therapeutic Targets for Cancers Deficient in the DNA Mismatch Repair Proteins, MSH2 or MLH1. Cancer Cell (2010) 17(3): 235-48. PMID: 20227038

Major Funding
  • 2018-2021- Barts Charity, Project grant: Identification of DNA damage signatures that predict response to immune checkpoint blockade, £252,000
Other Activities
  • Research Advisory Committee for Wellbeing of Women
  • Editorial Board member for Scientific Reports
  • Scientific Advisory Panel for Breast Cancer UK
  • Member of the British Lung Foundation College of Experts
Research

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.

Other Activities
  • Research Advisory Committee for Wellbeing of Women
  • Editorial Board member for Scientific Reports
  • Scientific Advisory Panel for Breast Cancer UK
  • Member of the British Lung Foundation College of Experts
  • Editorial Advisory Panel for the Biochemical Journal
  • Member of The British Association for Cancer Research
  • Member of the  Biochemical Society
Major Funding
  • 2018-2021- Barts Charity, Project grant: Identification of DNA damage signatures that predict response to immune checkpoint blockade, £252,000
  • 2016-2019- British Lung Foundation, Overcoming resistance to arginine deprivation therapy in mesothelioma, £149,076
  • 2012-2015- Medical Research Council, Characterization and impact of novel regulators of mitochondrial DNA integrity on tumourigenesis, £416,652

Recent Publications

MLH1 deficiency leads to deregulated mitochondrial metabolism Martin S Cell Death and Disease (2019) 10(1) 795-795

Targeting APC loss using synthetic lethality in Colorectal Cancer Shailes H, Bridge G, Foxler D et al. MOLECULAR CANCER THERAPEUTICS (2017) 16(11)
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000412270800022&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

Drug-repositioning screens identify triamterene as a selective drug for the treatment of DNA mismatch repair deficient cells Guillotin D, Austin P, Begum R et al. Clinical Cancer Research (2017) 23(7) 2880-2890

Inhibition of the Polyamine Synthesis Pathway Is Synthetically Lethal with Loss of Argininosuccinate Synthase 1 Locke M, Ghazaly E, Freitas MO et al. Cell Reports (2016) 16(1) 1604-1613

Inhibition of the polyamine synthesis pathway is synthetically lethal with loss of argininosuccinate synthase 1 in cancer Szlosarek PW, Locke M, Ghazaly E et al. CANCER RESEARCH (2016) 76(11)
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000389941706086&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

The DNA mismatch repair pathway Martin SA (2016) (7) 151-177

Reduced expression of histone methyltransferases KMT2C and KMT2D correlates with improved outcome in pancreatic ductal adenocarcinoma GROSE RP, Dawkins JBN, Wang J et al. Cancer Research (2016) (1)
http://www.bci.qmul.ac.uk/staff/item/richard-grose

Targeting Mismatch Repair defects: A novel strategy for personalized cancer treatment Begum R, Martin SA DNA Repair (2016) 38(7) 135-139

RAD51 and BRCA2 enhance oncolytic adenovirus type 5 activity in ovarian cancer Tookman LA, Browne AK, Connell CM et al. Molecular Cancer Research (2016) 14(7) 44-55

Targeting the mitochondria for the treatment of MLH1-deficient disease Rashid S, Bridge G, Yao Z et al. CANCER RESEARCH (2015) 75(11)
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000371597104341&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

For additional publications, please click here
Team

Postdoctoral Researchers in this group
Dr Marta FreitasDr Danilo Cucchi

PhD Students
Ms Josephine Carpentier, Ms Rebecca Downing, Ms Charlotte Smith, Ms Wai Yiu (Betty) Tse

Biography

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 identify 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.