Sheffield Institute for Nucleic Acids

Dr Helen Bryant

Research Interests

Dr Bryant has worked in the area of genome biology for 20 years. Her lab employs chemists, biologists and clinicians in order to promote a multi-disciplinary approach to translational research.

By understanding control of the fidelity of DNA replication in normal cells we aim to understand why defects in the proteins involved are associated with cancer. Her aim is to pinpoint differences between dividing tumour cells and dividing normal cells and determine which are important in cancer development. This has enabled the group to develop drugs which can specifically kill the tumour cells rather than just all dividing cells (personalized therapy).

To this ends there are 3 board themes that overlap in the lab.

  • Understanding of the cellular pathways activated when DNA replication is perturbed.
  • Identification of the changes in expression of these genes and phenotypic consequences in cancer
  • Exploitation of these changes in hypothesis driven drug development.

A separate side to Dr Bryant’s work is the development of novel photodynamic therapy agents that bind to DNA and induce damage only upon irradiation with specific wavelengths of light. This is a collaboration with Prof. Julia Weinstein in the Department of Chemistry (TUOS)


Publications

  • Rachel E. Doherty, Igor V. Sazanovich, Luke K. McKenzie, Alexander S. Stasheuski, Rachel Coyle, Elizabeth Baggaley, Sarah Bottomley, Julia A. Weinstein, Helen E. Bryant Photodynamic killing of cancer cells by a Platinum(II) complex with cyclometallating ligands. Nature Scientific Reports (accepted for publication) Feb 2016
  • Arora A, Abdel-Fatah TM, Agarwal D, Doherty R, Croteau DL, Moseley PM, Hameed K, Green A, Aleskandarany MA, Rakha EA, Patterson K, Ball G, Chan SY, Ellis IO, Bohr VA, Bryant HE, Madhusudan S. Clinicopathological and prognostic significance of RECQL5 helicase expression in breast cancers. Carcinogenesis. 2016 Jan;37(1):63-71.
  • Drayton RM, Peter S, Myers K, Miah S, Dudziec E, Bryant HE, Catto JW. MicroRNA-99a and 100 mediated upregulation of FOXA1 in bladder cancer. Oncotarget. 2014 Aug 30;5(15):6375-86.
  • Drayton RM, Dudziec E, Peter S, Bertz S, Hartmann A, Bryant HE, Catto JW. Reduced expression of miRNA-27a modulates cisplatin resistance in bladder cancer by targeting the cystine/glutamate exchanger SLC7A11. Clin Cancer Res. 2014 Apr 1;20(7):1990-2000.
  • Gravells P, Hoh L, Solovieva S, Patil A, Dudziec E, Rennie IG, Sisley K, Bryant HE. (2013) Reduced FANCD2 influences spontaneous SCE and RAD51 foci formation in uveal melanoma and Fanconi anaemia. Oncogene. 2013 Nov 14;32(46):5338-46
  • Fathers C, Drayton RM, Solovieva S, Bryant HE.(2012). Inhibition of poly(ADP-ribose) glycohydrolase (PARG) specifically kills BRCA2-deficient tumor cells. Cell Cycle. Mar 1;11(5). 990-997.
  • Gravells P, Hoh L, Canovas D, Rennie IG, Sisley K, Bryant HE. (2011) Resistance of uveal melanoma to the interstrand cross-linking agent mitomycin C is associated with reduced expression of CYP450R. Br J Cancer. Mar 29;104(7):1098-105.
  • Blundred R, Myers K, Helleday T, Goldman AS, Bryant HE. (2010) Human RECQL5 overcomes thymidine-induced replication stress. DNA Repair (Amst). Sep 4;9(9):964-75.
  • Bryant HE, Petermann E, Schultz N, Jemth AS, Loseva O, Issaeva N, Johansson F, Fernandez S, McGlynn P, Helleday T. (2009) PARP is activated at stalled forks to mediate Mre11-dependent replication restart and recombination. EMBO J. Sep 2;28(17):2601-15.
  • Ying S, Myers K, Bottomley S, Helleday T, Bryant HE. (2009) BRCA2-dependent homologous recombination is required for repair of Arsenite-induced replication lesions in mammalian cells. Nucleic Acids Res. Aug;37(15):5105-13.
  • Bryant HE, Helleday T. (2006) Inhibition of poly (ADP-ribose) polymerase activates ATM which is required for subsequent homologous recombination repair. Nucleic Acids Res. 34(6):1685-91.
  • Bryant HE., Saleh-Gohari N, , Schultz N, Parker KM, Cassel TN, Helleday T. (2005) Spontaneous homologous recombination is induced by collapsed replication forks that are caused by endogenous DNA single-strand breaks. Mol Cell Biol. 25(16):7158-69.
  • Bryant HE, Schultz N, Flower D, Lopez E, Kyle S, Meuth M, Curtin NJ, Helleday T. (2005) Specific killing of BRCA2 deficient cells by inhibitors of poly(ADP-ribose) polymerase. Nature 434(7035):913-7.
Dr Helen Bryant
Senior Lecturer
Department of Oncology and Metabolism
+44 (0)114 271 2993
h.bryant@sheffield.ac.uk