Dr Helen E Bryant

Senior LecturerHelen Bryant

Head of The DNA replication and repair group
Academic Unit of Molecular Oncology
Department of Oncology & Metabolism
The Medical School
Beech Hill Road
Sheffield
S10 2RX
United Kingdom

Telephone: +44 (0)114 215 9040
Email: h.bryant@sheffield.ac.uk
Twitter: @bryantlab1 

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).

A separate side to Dr Bryant’s work is the development of novel transition metal containing 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).

To this ends there are 4 board themes that overlap in the lab.

  • Understanding of the cellular pathways activated when DNA replication is perturbed.
  • Improving and understanding radiotherapy response
  • Identification of the changes in expression of these genes and phenotypic consequences in cancer
  • Exploitation of these changes in hypothesis driven drug development.
  • Chemical development of novel therapeutic agents (focus on PDT agents)

Currently projects examine these themes in Bladder, Breast, NSCLC, HNSCC and Neuroblastoma.

Biography

1991 - 1995  BSc  Medical Biochemistry University of Glasgow

1996 - 1999  PhD  MRC Virology Unit, Glasgow

2000 - 2003   Post-doctoral Researcher   Ludwig Institute of Cancer Research, St Mary´s Hospital, London.

2003 - 2007  Post-doctoral Researcher  YCR Institute for Cancer Studies, University of Sheffield.

2007 - 2012   RCUK Academic Fellow YCR  Institute for Cancer Studies, University of Sheffield.

2012 - 2013   Lecturer  Department of Oncology, University of Sheffield.

2013 - present  Senior Lecturer  Department of Oncology and Metabolism, University of Sheffield

Teaching Interests

2012 - Postgraduate certificate in Learning and Teaching

Fellow of the Higher Education Academy

MSc - Translational Oncology

MSc - Molecular Medicine

Undergraduate - Genome Stability & Genetic Change module

Key Publications

Doherty, R. E., Bryant, H. E., Valluru, M. K., Rennie, I. G., & Sisley, K. (2019). Increased non-homologous end joining makes DNA-PK a promising target for therapeutic intervention in uveal melanoma. Cancers, 11(9). doi:10.3390/cancers11091278

Aguilar Cosme, J. R., Bryant, H. E., & Claeyssens, F. (2019). Carbon dot-protoporphyrin IX conjugates for improved drug delivery and bioimaging. PLoS ONE, 14(7). doi:10.1371/journal.pone.0220210

Willan J., Cleasby A.J., Flores-Rodriguez N., Stefani F., Rinaldo C., Pisciottani A., Grant E., Woodman P., Bryant H.E., Ciani B. (2019). ESCRT-III is necessary for the integrity of the nuclear envelope in micronuclei but is aberrant at ruptured micronuclear envelopes generating damage. Oncogenesis, 8(5). doi:10.1038/s41389-019-0136-0

Crowston, B.J., Shipp, J.D., Chekulaev, D., McKenzie, Luke K., Jones, C., Weinstein, J.A., Meijer, A.J.H., Bryant, H.E., Natrajan, L., Woodward, A. Ward, M.D. Heteronuclear d-d and d-f Ru(II)/M complexes [M = Gd(III), Yb(III), Nd(III), Zn(II) or Mn(II)] of ligands combining phenanthroline and aminocarboxylate binding sites: combined relaxivity, cell imaging and photophysical studies. Dalton Transactions. doi:10.1039/c9dt00954j

Kadhim, A., McKenzie, L. K., Bryant, H. E., & Twyman, L. J. (2019). Synthesis and Aggregation of a Porphyrin-Cored Hyperbranched Polyglycidol and Its Application as a Macromolecular Photosensitizer for Photodynamic Therapy. Molecular Pharmaceutics, 16(3), 1132-1139. doi:10.1021/acs.molpharmaceut.8b01119

Omar SAE, Scattergood PA, McKenzie LK, Jones C, Patmore NJ, Meijer AJHM, Weinstein JA, Rice CR, Bryant HE, Elliott PIP. Photophysical and Cellular Imaging. Studies of Brightly Luminescent Osmium(II) Pyridyltriazole Complexes. Inorg Chem. 2018 Nov 5;57(21):13201-13212.

Daniels, R. E., McKenzie, L. K., Shewring, J. R., Weinstein, J. A., Kozhevnikov, V. N., & Bryant, H. E. (2018). Pyridazine-bridged cationic diiridium complexes as potential dual-mode bioimaging probes. RSC Advances, 8(18), 9670-9676.

Polly Gravells, James Neale, Emma Grant, Amit Nathubhai, Kate M. Smith, Dominic I. James and Helen E. Bryant. Radiosensitization with an inhibitor of poly(ADP-ribose) glycohydrolase; a comparison with the PARP1/2/3 inhibitor olaparib. DNA Repair, 61, 25-36.

Polly Gravells, Emma Grant, Kate M. Smith, Dominic I. James, Helen E. Bryant Specific killing of DNA damage-response deficient cells with inhibitors of poly(ADP-ribose) glycohydrolase DNA Repair, Volume 52, April 2017, Pages 81-91

McKenzie LK, Sazanovich IV, Baggaley E, Bonneau M, Guerchais V, Williams JA, Weinstein JA, Bryant HE. Metal Complexes for Two-Photon Photodynamic Therapy: A Cyclometallated Iridium Complex Induces Two-Photon Photosensitization of Cancer Cells under Near-IR Light. Chemistry. 2016 Oct 14. doi: 10.1002/chem.201604792. [Epub ahead of print] PubMed PMID: 27740703.

Patterson K, Arya L, Bottomley S, Morgan S, Cox A, Catto J, Bryant HE. Altered RECQL5 expression in urothelial bladder carcinoma increases cellular proliferation and makes RECQL5 helicase activity a novel target for chemotherapy. Oncotarget. 2016 Oct 15. doi: 10.18632/oncotarget.12683. [Epub ahead of print] PubMed PMID: 27764811.

Omar SA, Scattergood PA, McKenzie LK, Bryant HE, Weinstein JA, Elliott PI. Towards Water Soluble Mitochondria-Targeting Theranostic Osmium(II)Triazole-Based Complexes. Molecules. 2016 Oct 18;21(10). pii: E1382. PubMed PMID:27763561.

Jana A, Crowston BJ, Shewring JR, McKenzie LK, Bryant HE, Botchway SW, Ward AD, Amoroso AJ, Baggaley E, Ward MD. Heteronuclear Ir(III)-Ln(III) Luminescent Complexes: Small-Molecule Probes for Dual Modal Imaging and Oxygen Sensing. Inorg Chem. 2016 Jun 6;55(11):5623-33. doi: 10.1021/acs.inorgchem.6b00702. PubMed PMID:27219675.

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 ligand. Nature Scientific Reports 2016 Mar 4;6:22668.

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. (co-corresponding)

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-based compound, a derivative of Pt(II) dipyridobenzene. Photodiagnosis and Photodynamic Therapy. 2015 Sept 12(3):338–339

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. (co –corresponding)

Gravells P, Hoh L, Solovieva S, Patil A, Dudziec E, Rennie IG, Sisley K, Bryant HE. Reduced FANCD2 influences spontaneous SCE and RAD51 foci formation in uveal melanoma and Fanconi anaemia. Oncogene 2013 Jan ;14. doi: 10.1038/onc.2012.627. [Epub ahead of print]

Fathers C, Drayton RM, Solovieva S, Bryant HE. Inhibition of poly(ADP-ribose) glycohydrolase (PARG) specifically kills BRCA2-deficient tumor cells. Cell Cycle. 2012 Mar 1;11(5). 990-997

Gravells P, Hoh L, Canovas D, Rennie IG, Sisley K, Bryant H. Resistance of uveal melanoma to the interstrand cross-linking agent mitomycin C is associated with reduced expression of CYP450R. Br J Cancer. 2011 Mar 29;104(7):1098-105

Hoh L, Gravells P, Canovas D, Ul-Hassan A, Rennie IG, Bryant H, Sisley K. Atypically low spontaneous sister chromatid exchange formation in uveal melanoma. Genes Chromosomes Cancer. 2011 Jan;50(1):34-42.

Blundred R, Myers K, Helleday T, Goldman AS, Bryant HE. Human RECQL5 overcomes thymidine-induced replication stress. DNA Repair (Amst). 2010 Sep 4;9(9):964-75.

Gottipati P, Vischioni B, Schultz N, Solomons J, Bryant HE, Djureinovic T, Issaeva N, Sleeth K, Sharma RA, Helleday T. Poly(ADP-ribose) polymerase is hyperactivated in homologous recombination- defective cells. Cancer Res. 2010 Jul 1;70(13):5389-98.

Loseva O, Jemth AS, Bryant HE, Schüler H, Lehtiö L, Karlberg T, Helleday T. PARP-3 is a mono-ADP-ribosylase that activates PARP-1 in the absence of DNA. J Biol Chem. 2010 Mar 12;285(11):8054-60.

McLachlan J, Fernandez S, Helleday T, Bryant HE. Specific targeted gene repair using single-stranded DNA oligonucleotides at an endogenous locus in mammalian cells uses homologous recombination. DNA Repair (Amst). 2009 Dec 3;8(12):1424-33.

Catto JW, Miah S, Owen HC, Bryant H, Myers K, Dudziec E, Larré S, Milo M, Rehman I, Rosario DJ, Di Martino E, Knowles MA, Meuth M, Harris AL, Hamdy FC. Distinct microRNA alterations characterize high- and low-grade bladder cancer. Cancer Res. 2009 Nov 1;69(21):8472-81.

Al-Minawi AZ, Lee YF, Håkansson D, Johansson F, Lundin C, Saleh-Gohari N, Schultz N, Jenssen D, Bryant HE, Meuth M, Hinz JM, Helleday T. The ERCC1/XPF endonuclease is required for completion of homologous recombination at DNA replication forks stalled by inter-strand cross-links. Nucleic Acids Res. 2009 Oct;37(19):6400-13.

Bryant HE, Petermann E, Schultz N, Jemth AS, Loseva O, Issaeva N, Johansson F, Fernandez S, McGlynn P, Helleday T. PARP is activated at stalled forks to mediate Mre11-dependent replication restart and recombination. EMBO J. 2009 Sep 2;28(17):2601-15.

Ying S, Myers K, Bottomley S, Helleday T, Bryant HE. BRCA2-dependent homologous recombination is required for repair of Arsenite- induced replication lesions in mammalian cells. Nucleic Acids Res. 2009 Aug;37(15):5105-13.

Bryant HE, Ying S, Helleday T. Homologous recombination is involved in repair of chromium-induced DNA damage in mammalian cells. Mutat Res. 2006 Jul 25;599(1-2):116-23.

Bryant HE, Helleday T. Inhibition of poly (ADP-ribose) polymerase activates ATM which is required for subsequent homologous recombination repair. Nucleic Acids Res. 2006 Mar 23;34(6):1685-91.

Helleday T, Bryant HE, Schultz N. Poly(ADP-ribose) polymerase (PARP-1) in homologous recombination and as a target for cancer therapy. Cell Cycle. 2005 Sep;4(9):1176-8.

Bryant HE, Saleh-Gohari N, Schultz N, Parker KM, Cassel TN, Helleday T. Spontaneous homologous recombination is induced by collapsed replication forks that are caused by endogenous DNA single-strand breaks. Mol Cell Biol. 2005 Aug;25(16):7158-69.

Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, Kyle S, Meuth M, Curtin NJ, Helleday T. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005 Apr 14;434(7035):913-7.

Amon W, Binné UK, Bryant H, Jenkins PJ, Elgueta Karstegl C and Farrell PJ. Lytic cycle gene regulation of Epstein-Barr virus. J. Virol, 78(24):13460-9 (2004)

Bryant HE, Farrell PJ. Signal transduction and transcription factor modification during reactivation of Epstein-Barr virus from latency. J. Virol.Oct; 76(20):10290-98 (2002)

Bryant HE, Wadd SE, Lamond AI, Silverstein SJ, Clements JB. Herpes simplex virus IE63 (ICP27) protein interacts with spliceosome-associated protein 145 and inhibits splicing prior to the first catalytic step. J Virol.   May;75(9):4376-85 (2001)

Bryant HE, Matthews DA, Wadd S, Scott JE, Kean J, Graham S, Russell WC, Clements JB. Interaction between herpes simplex virus type 1 IE63 protein and cellular protein p32. J Virol. Dec;74(23):11322-8 (2000)

Bryant HE, Wadd S, Filhol O, Scott JE, Hsieh TY, Everett RD, Clements JB. The multifunctional herpes simplex virus IE63 protein interacts with heterogeneous ribonucleoprotein K and with casein kinase 2. J Biol Chem. Oct 8;274(41):28991-8 (1999)

For a full list of publications please visit myPublications

Bryant group