Professor Helen E Bryant
Clinical Medicine, School of Medicine and Population Health
Professor of Cancer Therapeutics
Head of The DNA replication and repair group
h.bryant@sheffield.ac.uk
GU11, G Floor, The Medical School
Full contact details
Professor Helen E Bryant
Clinical Medicine, School of Medicine and Population Health
GU11, G Floor
The Medical School
Beech Hill Road
Sheffield
S10 2RX
Clinical Medicine, School of Medicine and Population Health
GU11, G Floor
The Medical School
Beech Hill Road
Sheffield
S10 2RX
- Profile
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For enquiries please contact - SMPH-West-Operational@sheffield.ac.uk
- Qualifications
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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
- Research interests
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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 the 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 end 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)
Current projects examine these themes in Bladder, Breast, NSCLC, HNSCC and Neuroblastoma.
- Publications
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Journal articles
- Photostable Iridium(III) Cyclometallated Complex is an Efficient Photosensitizer for Killing Multiple Cancer Cell Lines and 3D Models under Low Doses of Visible Light.. J Med Chem.
- Gelatin-containing porous polycaprolactone PolyHIPEs as substrates for 3D breast cancer cell culture and vascular infiltration. Frontiers in Bioengineering and Biotechnology, 11. View this article in WRRO
- 18P AURKB inhibition radiosensitises NSCLC by altering mitotic fate. ESMO Open, 8(1), 101664-101664.
- Abstract 3542: A stem cell model dissects detrimental effects of neuroblastoma-linked chromosomal aberrations on cell differentiation during neural crest development. Cancer Research, 83(7_Supplement), 3542-3542.
- Increased replication stress determines ATR inhibitor sensitivity in neuroblastoma cells. Cancers, 13(24).
- Morphological response in cancer spheroids for screening photodynamic therapy parameters. Frontiers in Molecular Biosciences, 8(11). View this article in WRRO
- In Vitro Low-Fluence Photodynamic Therapy Parameter Screening Using 3D Tumor Spheroids Shows that Fractionated Light Treatments Enhance Phototoxicity.. ACS Biomater Sci Eng.
- PrimPol-dependent single-stranded gap formation mediates homologous recombination at bulky DNA adducts. Nature Communications, 11(1). View this article in WRRO
- DNA fiber assay for the analysis of DNA replication progression in human pluripotent stem cells. Current Protocols in Stem Cell Biology, 54(1). View this article in WRRO
- Therapeutic vulnerabilities in the DNA damage response for the treatment of ATRX mutant neuroblastoma. EBioMedicine, 59.
- Poly(ADP-Ribose) glycohydrolase (PARG) vs. poly(ADP-Ribose) polymerase (PARP) – function in genome maintenance and relevance of inhibitors for anti-cancer therapy. Frontiers in Molecular Biosciences, 7.
- MYCN expression induces replication stress and sensitivity to PARP inhibition in neuroblastoma. Oncotarget, 11(23), 2141-2159. View this article in WRRO
- Investigation of the role of VHL-HIF signaling in DNA repair and apoptosis in zebrafish. Oncotarget, 11(13), 1109-1130. View this article in WRRO
- Increased non-homologous end joining makes DNA-PK a promising target for therapeutic intervention in uveal melanoma. Cancers, 11(9). View this article in WRRO
- Carbon dot-protoporphyrin IX conjugates for improved drug delivery and bioimaging. PLoS ONE, 14(7). View this article in WRRO
- 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). View this article in WRRO
- 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. View this article in WRRO
- 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. View this article in WRRO
- Photophysical and Cellular Imaging Studies of Brightly Luminescent Osmium(II) Pyridyltriazole Complexes. Inorganic Chemistry. View this article in WRRO
- Transition metal complexes as photosensitisers in one- and two-photon photodynamic therapy. Coordination Chemistry Reviews. View this article in WRRO
- Pyridazine-bridged cationic diiridium complexes as potential dual-mode bioimaging probes. RSC Advances, 8(18), 9670-9676. View this article in WRRO
- Radiosensitization with an inhibitor of poly(ADP-ribose) glycohydrolase: A comparison with the PARP1/2/3 inhibitor olaparib. DNA Repair, 61, 25-36. View this article in WRRO
- Specific killing of DNA damage-response deficient cells with inhibitors of poly(ADP-ribose) glycohydrolase. DNA Repair, 52, 81-91. View this article in WRRO
- DNA Repair in Prostate Cancer: Biology and Clinical Implications.. European Urology, 71(3), 417-425. View this article in WRRO
- Metal Complexes For Two-photon Photodynamic Therapy: A Cyclometallated Iridium Complex Induces Two-photon Photosensitization of Cancer Cells Under Near-IR Light.. Chemistry - A European Journal, 23(2), 234-238. View this article in WRRO
- Frontispiece: Metal Complexes for Two-Photon Photodynamic Therapy: A Cyclometallated Iridium Complex Induces Two-Photon Photosensitization of Cancer Cells under Near-IR Light. Chemistry - A European Journal, 23(2), 234-234.
- DNA damage repair in breast cancer and its therapeutic implications. Pathology.
- Towards Water Soluble Mitochondria-Targeting Theranostic Osmium(II) Triazole-Based Complexes.. Molecules, 21(10). View this article in WRRO
- Altered RECQL5 expression in urothelial bladder carcinoma increases cellular proliferation and makes RECQL5 helicase activity a novel target for chemotherapy.. Oncotarget. View this article in WRRO
- The Clinical Impact of BRCA2 Loss in Prostate Cancer. European Urology, 69(6), 996-997.
- Heteronuclear Ir(III)–Ln(III) Luminescent Complexes: Small-Molecule Probes for Dual Modal Imaging and Oxygen Sensing. Inorganic Chemistry, 55(11), 5623-5633. View this article in WRRO
- Photodynamic killing of cancer cells by a Platinum(II) complex with cyclometallating ligand. Scientific Reports, 6. View this article in WRRO
- Clinicopathological and prognostic significance of RECQL5 helicase expression in breast cancers. Carcinogenesis, 37(1), 63-71. View this article in WRRO
- Photodynamic killing of cancer cells by a platinum-based compound, a derivative of Pt(II) dipyridobenzene. Photodiagnosis and Photodynamic Therapy, 12(3), 338-339.
- 426 Identification and diagnostic performance of a small RNA within the PCA3 and BMCC1 gene locus that potentially targets mRNA. European Urology Supplements, 14(2), e426-e426b.
- PI3King the Lock. Journal of Pediatric Hematology/Oncology, 37(4), 245-251.
- Identification and Diagnostic Performance of a Small RNA within the PCA3 and BMCC1 Gene Locus That Potentially Targets mRNA. Cancer Epidemiology Biomarkers & Prevention, 24(1), 268-275. View this article in WRRO
- ‘Sex’ in the cancer cell. Oncotarget, 5(18), 7984-7985. View this article in WRRO
- MicroRNA-99a and 100 mediated upregulation of FOXA1 in bladder cancer. Oncotarget, 5(15), 6375-6386. View this article in WRRO
- Reduced expression of miRNA-27a modulates cisplatin resistance in bladder cancer by targeting the cystine/glutamate exchanger SLC7A11.. Clin Cancer Res, 20(7), 1990-2000. View this article in WRRO
- Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer. Breast Cancer Research(5), R92. View this article in WRRO
- Reduced FANCD2 influences spontaneous SCE and RAD51 foci formation in uveal melanoma and Fanconi anaemia.. Oncogene, 32(46), 5338-5346. View this article in WRRO
- PARP-3 is a mono-ADP-ribosylase that activates PARP-1 in the absence of DNA.: FIGURE 2.. Journal of Biological Chemistry, 287(41), 34494-34494.
- Inhibition of poly(ADP-ribose) glycohydrolase (PARG) specifically kills BRCA2-deficient tumor cells.. Cell Cycle, 11(5), 990-997.
- Abstract A10: MicroRNA 27a is downreguated in cisplatin resistant bladder cancer cells, and contributes to resistance through the targeting of xCT, a cystine transporter involved with glutathione production. Cancer Research, 72(2 Supplement), A10-A10.
- DNA double-strand break damage and repair assessed by pulsed-field gel electrophoresis.. Methods Mol Biol, 920, 315-321.
- Resistance of uveal melanoma to the interstrand cross-linking agent mitomycin C is associated with reduced expression of CYP450R.. Br J Cancer, 104(7), 1098-1105. View this article in WRRO
- Atypically low spontaneous sister chromatid exchange formation in uveal melanoma.. Genes Chromosomes Cancer, 50(1), 34-42.
- Human RECQL5 overcomes thymidine-induced replication stress.. DNA Repair (Amst), 9(9), 964-975.
- Poly(ADP-ribose) polymerase is hyperactivated in homologous recombination-defective cells.. Cancer Res, 70(13), 5389-5398.
- PARP-3 Is a Mono-ADP-ribosylase That Activates PARP-1 in the Absence of DNA. J BIOL CHEM, 285(11), 8054-8060.
- Specific targeted gene repair using single-stranded DNA oligonucleotides at an endogenous locus in mammalian cells uses homologous recombination.. DNA Repair (Amst), 8(12), 1424-1433.
- Distinct microRNA alterations characterize high- and low-grade bladder cancer.. Cancer Res, 69(21), 8472-8481.
- The ERCC1/XPF endonuclease is required for completion of homologous recombination at DNA replication forks stalled by inter-strand cross-links.. Nucleic Acids Res, 37(19), 6400-6413. View this article in WRRO
- PARP is activated at stalled forks to mediate Mre11-dependent replication restart and recombination.. EMBO J, 28(17), 2601-2615.
- BRCA2-dependent homologous recombination is required for repair of Arsenite-induced replication lesions in mammalian cells.. Nucleic Acids Res, 37(15), 5105-5113. View this article in WRRO
- A function for PARP at stalled replication forks. MUTAGENESIS, 22(6), 431-431.
- Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature, 447(7142), 346-346.
- Homologous recombination is involved in repair of chromium-induced DNA damage in mammalian cells.. Mutat Res, 599(1-2), 116-123.
- Inhibition of poly (ADP-ribose) polymerase activates ATM which is required for subsequent homologous recombination repair.. Nucleic Acids Res, 34(6), 1685-1691. View this article in WRRO
- Poly(ADP-ribose) polymerase (PARP-1) in homologous recombination and as a target for cancer therapy.. Cell Cycle, 4(9), 1176-1178.
- Spontaneous homologous recombination is induced by collapsed replication forks that are caused by endogenous DNA single-strand breaks.. Mol Cell Biol, 25(16), 7158-7169.
- Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase.. Nature, 434(7035), 913-917.
- Lytic cycle gene regulation of Epstein-Barr virus.. J Virol, 78(24), 13460-13469.
- Poly(ADP-ribose) polymerase inhibitors as potential chemotherapeutic agents.. Biochem Soc Trans, 32(Pt 6), 959-961.
- Signal Transduction and Transcription Factor Modification during Reactivation of Epstein-Barr Virus from Latency.. J Virol, 76(20), 10290-10298.
- Herpes simplex virus IE63 (ICP27) protein interacts with spliceosome-associated protein 145 and inhibits splicing prior to the first catalytic step.. J Virol, 75(9), 4376-4385.
- Interaction between herpes simplex virus type 1 IE63 protein and cellular protein p32.. J Virol, 74(23), 11322-11328.
- The multifunctional herpes simplex virus IE63 protein interacts with heterogeneous ribonucleoprotein K and with casein kinase 2.. J Biol Chem, 274(41), 28991-28998.
- A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations. Nature Communications, 15(1).
- Targeting OGG1 and PARG radiosensitises head and neck cancer cells to high-LET protons through complex DNA damage persistence. Cell Death & Disease, 15(2).
- Phototoxicity of cyclometallated Ir(III) complexes bearing a thio-bis-benzimidazole ligand, and its monodentate analogue, as potential PDT photosensitisers in cancer cell killing. JBIC Journal of Biological Inorganic Chemistry.
- Magnetosomes and Magnetosome Mimics: Preparation, Cancer Cell Uptake and Functionalization for Future Cancer Therapies. Pharmaceutics, 13(3), 367-367.
Chapters
- Refining a correlative light electron microscopy workflow using luminescent metal complexes, Methods in Cell Biology (pp. 69-87). Elsevier
- Synthetic Lethality with Homologous Recombination Repair Defects, Cancer Drug Discovery and Development (pp. 315-344). Springer International Publishing
Conference proceedings papers
- Production of porous polycaprolactone polyHIPEs as substrates for in vitro 3D breast cancer cell culture. TISSUE ENGINEERING PART A, Vol. 29(13-14)
- Production of porous polycaprolactone polyHIPEs as substrates for in vitro 3D breast cancer cell culture. TISSUE ENGINEERING PART A, Vol. 29(13-14)
- Investigation of Aurora Kinase A as a Potential Biomarker of Radiation in Non-Small Cell Lung Cancer (NSCLC). JOURNAL OF THORACIC ONCOLOGY, Vol. 16(10) (pp S1163-S1164)
- Artificial Neural Network-Based Tumour Recurrence Prediction in Non-Small Cell Lung Cancer Patients Following Radical Radiotherapy. JOURNAL OF THORACIC ONCOLOGY, Vol. 16(10) (pp S958-S958)
- Investigating the effect of replication stress and other phenotypic factors as determinants of sensitivity to single agent ATR inhibitor, VE-821 in ovarian cancer cell lines. EUROPEAN JOURNAL OF CANCER, Vol. 103 (pp E32-E32)
- UPR Activation via glucose deprivation and depletion of GRP78 protein (using siRNA) do not alter radiosensitivity in the human breast cancer cell line MCF7. EUROPEAN JOURNAL OF CANCER, Vol. 49 (pp S425-S425)
- Preclinical Investigation of Inhibition of the DNA Damage Response as a Targetted Therapy in Myeloproliferative Neoplasms Shows Synergism of ATR Inhibitors with Standard-of-Care Treatment. The 1st International Electronic Conference on Cancers: Exploiting Cancer Vulnerability by Targeting the DNA Damage Response, Vol. 129 (pp 17-17)
Preprints
- Under or Over? Tracing Complex DNA Topologies with High Resolution Atomic Force Microscopy, Cold Spring Harbor Laboratory.
- Neuroblastoma-associated chromosomal aberrations drive cell identity loss in human neural crest via disruption of developmental regulators, Cold Spring Harbor Laboratory.
- PrimPol-dependent single-stranded gap formation mediates homologous recombination at bulky DNA adducts, Cold Spring Harbor Laboratory.
- The investigation of the role of VHL-HIF signaling in DNA repair and apoptosis in zebrafish, Cold Spring Harbor Laboratory.
- ESCRT-III accumulates in micronuclei with ruptured nuclear envelopes, Cold Spring Harbor Laboratory.
- Photostable Iridium(III) Cyclometallated Complex is an Efficient Photosensitizer for Killing Multiple Cancer Cell Lines and 3D Models under Low Doses of Visible Light.. J Med Chem.
- Research group
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- Polly Gravells - Postdoctoral Research (Biologist)
- David King - Clinical Lecturer
- Saskia Roetschke - Clinical Research Fellow
- Marta Martinez - Postdoctoral Researcher (Chemist)
- Emma Grant - Postgraduate Student
- Callum Jones - Postgraduate Student
- Chris Legge - Postgraduate Student
- Thomas Jones - Postgraduate Student
- Fatma Bucklain - Postgraduate Student
- Hannah Gagg - Technician
- Teaching interests
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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