Dr Helen E Bryant

Lecturer

Molecular Oncology
Department of Oncology
The Medical School
Beech Hill Road
Sheffield
S10 2RX
United Kingdom

Telephone: +44 (0)114 271 2993
Facsimilie: +44 (0)114 271 1602
Email: h.bryant@sheffield.ac.uk

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 -
Lecturer
Department of Oncology, University of Sheffield.

Research Interests

A key stage in cell division is the copying of DNA (DNA replication). The proteins involved in replication (the replication complex) move along DNA copying it, however, if they come across a section of DNA that is damaged, replication stops. At this point multiple proteins are activated, they serve to stabilise the replication complex and help by-pass or correct the problem. If the damage is too great to repair, normal cells have a self-destruct mechanism called apoptosis. Through repair and apoptosis normal cells ensure that damage in DNA is not passed to their daughter cells, this is important as damage can lead to dysfunction of the proteins encoded in that section of DNA and thus to cellular dysfunction and disease.

In cancer cells there can be defects in the repair and apoptosis pathways which cause inaccurate copying of DNA and further contribute to the cancer. Chemotherapy causes massive damage to DNA at the point of cell division, in this way in dividing cells it triggers cell death (hence the tumour dies and we see side effects in normal tissue). Some cancers can also become resistant to chemotherapy as they no longer have a functional self-destruct mechanism. In these cases the tumour continues to grow with increasing amounts of damage being passed onto the new tumour cells.

The aim of my research is to understand what happens in a cell when DNA replication is slowed or stopped by damage in DNA. I want to understand which proteins bind to the arrested DNA, whether they are modified in any way and what significance this has on the reestablishment of replication.
By understanding the normal control mechanisms in cells I aim to understand why defects in the proteins involved are associated with cancer. I want to pinpoint differences between dividing tumour cells and dividing normal cells and determine which are important in cancer development. This will enable us to develop drugs which can specifically kill the tumour cells rather than just all dividing cells.

We have particular interests in the mechanisms of genetic instability in bladder, breast and uveal cancer and enjoy close ties with our clinical colleagues in the Royal Hallamshire Hospital (including several joint projects). This enables us to translate our research quickly into potential therapies.

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

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)