Staff Profile
Professor Neil Perkins
Prof of Gene Exp & Signalling
- Email: [email protected]
- Telephone: +44 (0) 191 208 2245
- Address: Newcastle University Biosciences Institute
Faculty of Medical Sciences
Herschel Building, Level 6
Brewery Lane
Newcastle upon Tyne
NE1 7RU
United Kingdom
Background
My PhD was completed in Graham Goodwin's laboratory at the Chester Beatty Laboratories, Institute of Cancer Research, London in 1990. This work concerned the investigation of chicken beta globin gene expression and resulted in the identification of the transcription factor that later became known as GATA1 (known as EF1 in the Goodwin lab).
From 1990 to 1996 I was a postdoctoral researcher in Gary Nabel's laboratory, at the Howard Hughes Medical Institute at the University of Michigan, where my interest in the NF-kappaB transcription factor family began. Much of this work concerned the ability of NF-appaB to function as a regulator of human immunodeficiency virus (HIV) 1.
Previous Positions
October 1986 - March 1990: Ph.D. student in the laboratory of Dr. Graham Goodwin, Chester Beatty Laboratories, Institute of Cancer Research.
March 1990- March 1996: Postdoctoral Fellow in the laboratory of Prof. Gary J. Nabel, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, MI, USA.
March 1996 – Nov 2007: Lecturer and then Reader, Principal Investigator, University of Dundee
October 1996 - September 2005: Royal Society University Research Fellow
Nov 2007 – June 2008: Professor of Gene Expression and Signalling in the Wellcome Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee
July 2008 – March 2010: Professor of Molecular Cell Biology, Department of Cellular & Molecular Medicine, University of Bristol
April 2010 - present: Professor of Gene Expression and Signalling, Newcastle University
November 2019 - present: Deputy Dean - Biosciences Institute
November 2019 - present: Theme Lead - Cell Signalling
Regulation of cancer cell proliferation and survival by NF-kappaB
NF-kappaB is a collective name for the complexes formed by the multigene NF-kappaB-Rel family which function as DNA-binding proteins and transcription factors. NF-kappaB subunits induce the expression of a wide range of genes encoding proteins involved in inflammation, regulation of cell death, cell adhesion, proliferation and other critical cellular functions. Aberrant activation of NF-kappaB therefore leads to overproduction of these proteins, which can contribute to many types of human disease. In particular, NF-kappaB has an important role in many inflammatory diseases and cancer. Moreover, NF-kappaB is activated by many cancer therapies and can have an inhibitory effect on these treatments. The pathways regulating NF-kappaB are therefore thought to be good targets for the development of new anti-inflammatory and anti-cancer drugs.
My laboratory is interested in how NF-kappaB subunits are regulated by oncogenes, tumour suppressors and stimuli associated with cancer development and therapy. A theme emerging from these studies has been the importance of context for NF-kappaB activity and how subunits can both repress as well as activate gene targets, leading to alterations in cell fate. We have revealed the importance of post-translational modifications in controlling these activities and argued that the activity of parallel signalling pathways have a critical role in determining NF-kappaB dependent transcriptional output. Based on this work, together with that from other researchers, we propose that the concerted action of tumour suppressors functions to keep the oncogenic activities of NF-kappaB subunits in check and that loss of tumour suppressor activity during tumour development is required to unleash these anti apoptotic and pro-metastatic activities in malignant cancer cells.
CMB2001:Control of Eukaryotic Gene Expression
BGM2002:Biochemistry and Genetics of Signalling and the Cell Cycle
BGM3065:Biochemistry of Cancer and Chronic Diseases
MMB8050: Therapeutic Applications of Cell Signalling
- Madgwick S, Luli S, Sellier H, Butterworth JA, Leslie J, Moore AJ, Corbin EK, Yemm AI, Chiremba RT, Tiniakos D, Oakley F, Perkins ND, Hunter JE. Claspin haploinsufficiency leads to defects in fertility, hyperplasia and an increased oncogenic potential. Biochemical Journal 2022, 479(19), 2115-2130.
- Leslie J, Hunter JE, Collins A, Rushton A, Russell LG, Ramon-Gil E, Laszczewska M, McCain M, Zaki MYW, Knox A, Seow Y, Sabater L, Geh D, Perkins ND, Reeves HL, Tiniakos D, Mann DA, Oakley F. c-Rel–dependent Chk2 signaling regulates the DNA damage response limiting hepatocarcinogenesis. Hepatology 2023, 78(4), 1050-1063.
- Hunter JE, Campbell AE, Butterworth JA, Sellier H, Hannaway NL, Luli S, Floudas A, Kenneth NS, Moore AJ, Brownridge PJ, Thomas HD, Coxhead J, Taylor L, Leary P, Hasoon MSR, Knight AM, Garrett MD, Collins I, Eyers CE, Perkins ND. Mutation of the RelA(p65) Thr505 phosphosite disrupts the DNA replication stress response leading to CHK1 inhibitor resistance. Biochemical Journal 2022, 479(19), 2087-2113.
- Hunter JE, Campbell AE, Hannaway NL, Kerridge S, Luli S, Butterworth JA, Sellier H, Mukherjee R, Dhillon N, Sudhindar PD, Shukla R, Brownridge PJ, Bell HL, Coxhead J, Taylor L, Leary P, Hasoon MSR, Collins I, Garrett MD, Eyers CE, Perkins ND. Regulation of CHK1 inhibitor resistance by a c-Rel and USP1 dependent pathway. Biochemical Journal 2022, 479(19), 2063-2086.
- Hunter JE, Campbell AE, Kerridge S, Fraser C, Hannaway NL, Luli S, Ivanova I, Brownridge PJ, Coxhead J, Taylor L, Leary P, Hasoon MSR, Eyers CE, Perkins ND. Up-regulation of the PI3K/AKT and RHO/RAC/PAK signalling pathways in CHK1 inhibitor resistant Eµ-Myc lymphoma cells. Biochemical Journal 2022, 479(19), 2131-2151.
- Sandhu S, Sou IF, Hunter JE, Salmon L, Wilson CL, Perkins ND, Hunter N, Davies OR, McClurg UL. Centrosome dysfunction associated with somatic expression of the synaptonemal complex protein TEX12. Communications Biology 2021, 4(1), 1371.
- Campbell AE, Franco CF, Su L-I, Corbin EK, Perkins S, Kalyuzhnyy A, Jones AR, Brownridge PJ, Perkins ND, Eyers CE. Temporal modulation of the NF-B RelA network in response to different types of DNA damage. Biochemical Journal 2021, 478(3), 533-551.
- Dura G, Peters DT, Waller H, Yemm AI, Perkins ND, Ferreira AM, Crespo-Cuadrado M, Lakey JH, Fulton DA. A thermally reformable protein polymer. Chem 2020, 6(11), 3132-3151.
- Smith ALM, Whitehall JC, Bradshaw C, Gay D, Robertson F, Blain AP, Hudson G, Pyle A, Houghton D, Hunt M, Sampson JN, Stamp C, Mallett G, Amarnath S, Leslie J, Oakley F, Wilson L, Baker A, Russell OM, Johnson R, Richardson CA, Gupta B, McCallum I, McDonald SAC, Kelly S, Mathers JC, Heer R, Taylor RW, Perkins ND, Turnbull DM, Sansom OJ, Greaves LC. Age-associated mitochondrial DNA mutations cause metabolic remodeling that contributes to accelerated intestinal tumorigenesis. Nature Cancer 2020, 1, 976-989.
- Ivanova IG, Perkins ND. Hypoxia induces rapid, STAT3 and ROS dependent, mitochondrial translocation of RelA(p65) and IκBα. Bioscience Reports 2019, 39(9), BSR20192101.
- Al-Jawdah AD, Ivanova IG, Waller H, Perkins ND, Lakey JH, Peters DT. Induction of the immunoprotective coat of Yersinia pestis at body temperature is mediated by the Caf1R transcription factor. BMC Microbiology 2019, 19(1), 68.
- Szoltysek K, Janus P, Zajac G, Stokowy T, Walaszczyk A, Widlak W, Wojtas B, Gielniewski B, Cockell S, Perkins ND, Kimmel M, Widlak P. RRAD, IL4I1, CDKN1A, and SERPINE1 genes are potentially co-regulated by NF-κB and p53 transcription factors in cells exposed to high doses of ionizing radiation. BMC Genomics 2018, 19(1), 813.
- Perkins ND. More than just an IκB kinase: the IKK complex coordinates mRNA stability and transcription. EMBO Journal 2018, 37(24), e101084.
- Moles A, Butterworth JA, Sanchez A, Hunter JE, Leslie J, Sellier H, Tiniakos D, Cockell SJ, Mann DA, Oakley F, Perkins ND. A RelA(p65) Thr505 phospho-site mutation reveals an important mechanism regulating NF-kB dependent liver regeneration and cancer. Oncogene 2016, 35(35), 4623-4632.
- Hunter JE, Leslie J, Perkins ND. c-Rel and its many roles in cancer: an old story with new twists. British Journal of Cancer 2016, 114(1), 1-6.
- Walton MI, Eve PD, Hayes A, Henley AT, Valenti MR, Brandon AKD, Box G, Boxall KJ, Tall M, Swales K, Matthews TP, McHardy T, Lainchbury M, Osborne J, Hunter JE, Perkins ND, Aherne GW, Reader JC, Raynaud FI, Eccles SA, Collins I, Garrett MD. The clinical development candidate CCT245737 is an orally active CHK1 inhibitor with preclinical activity in RAS mutant NSCLC and Eμ-MYC driven B-cell lymphoma. Oncotarget 2016, 7(3), 2329-2342.
- Hunter JE, Butterworth JA, Zhao B, Sellier H, Campbell KJ, Thomas HD, Bacon CM, Cockell SJ, Gewurz BE, Perkins ND. The NF-κB subunit c-Rel regulates Bach2 tumour suppressor expression in B-cell lymphoma. Oncogene 2016, 35(26), 3476-3484.
- Tavora B, Reynolds LE, Batista S, Demircioglu F, Fernandez I, Lechertier T, Lees DM, Wong PP, Alexopoulou A, Elia G, Clear A, Ledoux A, Hunter J, Perkins N, Gribben JG, Hodivala-Dilke KM. Endothelial-cell FAK targeting sensitizes tumours to DNA-damaging therapy. Nature 2014, 514(7520), 112-116.
- Ledoux AC, Perkins ND. NF-kB and the cell cycle. Biochemical Society Transactions 2014, 42(1), 76-81.
- Harte MT, Gorski JJ, Savage KI, Purcell JW, Barros EW, Burn PM, McFarlane C, Mullan PB, Kennedy RD, Perkins ND, Harkin DP. NF-kappa B is a critical mediator of BRCA1-induced chemoresistance. Oncogene 2014, 33(6), 713-723.
- Iannetti A, Ledoux AC, Tudhope SJ, Sellier H, Zhao B, Mowla S, Moore A, Hummerich H, Gewurz BE, Cockell SJ, Jat PS, Willmore E, Perkins ND. Regulation of p53 and Rb Links the Alternative NF-kappaB Pathway to EZH2 Expression and Cell Senescence. PLoS Genetics 2014, 10(9), e1004642.
- Hunter JE, Butterworth J, Perkins ND, Bateson M, Richardson CA. Using body temperature, food and water consumption as biomarkers of disease progression in mice with Eμ-myc lymphoma. British Journal of Cancer 2014, 110, 928-934.
- Perkins ND. Emerging from NF-kappa B's Shadow, SUMOylated I kappa B alpha Represses Transcription. Cancer Cell 2013, 24(2), 139-140.
- Yamada K, Ono M, Perkins ND, Rocha S, Lamond AI. Identification and Functional Characterization of FMN2, a Regulator of the Cyclin-Dependent Kinase Inhibitor p21. Molecular Cell 2013, 49(5), 922-933.
- Moles A, Sanchez AM, Banks PS, Murphy LB, Luli S, Borthwick L, Fisher A, O'Reilly S, van Laar JM, White SA, Perkins ND, Burt AD, Mann DA, Oakley F. Inhibition of RelA-Ser536 phosphorylation by a competing peptide reduces mouse liver fibrosis without blocking the innate immune response. Hepatology 2013, 57(2), 817-828.
- Ledoux AC, Sellier H, Gillies K, Iannetti A, James J, Perkins ND. NF kappa B regulates expression of Polo-like kinase 4. Cell Cycle 2013, 12(18), 3052-3062.
- Southern SL, Collard TJ, Urban BC, Skeen VR, Smartt HJ, Hague A, Oakley F, Townsend PA, Perkins ND, Paraskeva C, Williams AC. BAG-1 interacts with the p50-p50 homodimeric NF-kappa B complex: implications for colorectal carcinogenesis. Oncogene 2012, 31(22), 2761-2772.
- Perkins ND. Cysteine 38 Holds the Key to NF-kappa B Activation. Molecular Cell 2012, 45(1), 1-3.
- Johnson RF, Perkins ND. Nuclear factor-kappa B, p53, and mitochondria: regulation of cellular metabolism and the Warburg effect. Trends in Biochemical Sciences 2012, 37(8), 317-324.
- Perkins ND. The diverse and complex roles of NF-kappa B subunits in cancer. Nature Reviews. Cancer 2012, 12(2), 121-132.
- Johnson RF, Witzel II, Perkins ND. p53-dependent regulation of mitochondrial energy production by the RelA subunit of NF-κB. Cancer Research 2011, 71(16), 5588-5597.
- Msaki A, Sanchez AM, Koh LF, Barre B, Rocha S, Perkins ND, Johnson RF. The role of RelA (p65) threonine 505 phosphorylation in the regulation of cell growth, survival, and migration. Molecular Biology of the Cell 2011, 22(17), 3032-3040.
- O'Shea JM, Perkins ND. Thr(435) phosphorylation regulates RelA (p65) NF-kappa B subunit transactivation. Biochemical Journal 2010, 426(3), 345-354.
- Bracken CP, Wall SJ, Barré B, Panov KI, Ajuh PM, Perkins ND. Regulation of cyclin D1 RNA stability by SNIP1. Cancer Research 2008, 68(18), 7621-7628.
- O'Shea JM, Perkins ND. Regulation of the ReIA (p65) transactivation domain. Biochemical Society Transactions 2008, 36(4), 603-608.
- Perkins ND. Integrating cell-signalling pathways with NF-kappaB and IKK function. Nature Reviews Molecular Cell Biology 2007, 8(1), 49-62.
- Tergaonkar V, Perkins ND. p53 and NF-κB crosstalk: IKKα tips the balance. Molecular Cell 2007, 26(2), 158-159.
- McTavish N, Copeland LA, Saville MK, Perkins ND, Spruce BA. Proenkephalin assists stress-activated apoptosis through transcriptional repression of NF-kappaB- and p53-regulated gene targets. Cell Death and Differentiation 2007, 14(9), 1700-1710.
- Roche KC, Rocha S, Bracken CP, Perkins ND. Regulation of ATR-dependent pathways by the FHA domain containing protein SNIP1. Oncogene 2007, 26(31), 4523-4530.
- Sharif O, Bolshakov VN, Raines S, Newham P, Perkins ND. Transcriptional profiling of the LPS induced NF-κB response in macrophages. BMC Immunology 2007, 8, 1.
- Campbell KJ, Witty JM, Rocha S, Perkins ND. Cisplatin mimics ARF tumor suppressor regulation of RelA (p65) nuclear factor-kappaB transactivation. Cancer Research 2006, 66(2), 929-935.
- Campbell KJ, O'Shea JM, Perkins ND. Differential regulation of NF-κB activation and function by topoisomerase II inhibitors. BMC Cancer 2006, 6, 101.
- Perkins ND, Gilmore TD. Good cop, bad cop: the different faces of NF-kappaB. Cell Death and Differentiation 2006, 13(5), 759-772.
- Perkins ND. Post-translational modifications regulating the activity and function of the nuclear factor kappa B pathway. Oncogene 2006, 25(51), 6717-6730.
- Schumm K, Rocha S, Caamano J, Perkins ND. Regulation of p53 tumour suppressor target gene expression by the p52 NF-kappaB subunit. The EMBO Journal 2006, 25(20), 4820-4832.
- Fujii M, Lyakh LA, Bracken CP, Fukuoka J, Hayakawa M, Tsukiyama T, Soil SJ, Harris M, Rocha S, Roche KC, Tominaga SI, Jen J, Perkins ND, Lechleider RJ, Roberts AB. SNIP1 is a candidate modifier of the transcriptional activity of c-Myc on E box-dependent target genes. Molecular Cell 2006, 24(5), 771-783.
- Rocha S, Perkins ND. ARF the integrator: linking NF-kappaB, p53 and checkpoint kinases. Cell Cycle 2005, 4(6), 756-759.
- Garcia-Wilson E, Perkins ND. p21(WAF1/CIP1) regulates the p300 sumoylation motif CRD1 through a C-terminal domain independently of Cyclin/CDK binding. Cell Cycle 2005, 4(8), 1113-1119.
- Rocha S, Garrett MD, Campbell KJ, Schumm K, Perkins ND. Regulation of NF-kappaB and p53 through activation of ATR and Chk1 by the ARF tumour suppressor. The EMBO Journal 2005, 24(6), 1157-1169.
- Bates GJ, Nicol SM, Wilson BJ, Jacobs AMF, Bourdon JC, Wardrop J, Gregory DJ, Lane DP, Perkins ND, Fuller-Pace FV. The DEAD box protein p68: a novel transcriptional coactivator of the p53 tumour suppressor. The EMBO Journal 2005, 24(3), 543-553.