Dr Martin R. Higgs

Martin Higgs

Institute of Cancer and Genomic Sciences
Associate Professor for Genomics and Rare Disease
Deputy Director, Centre for Rare Disease Studies

Contact details

Telephone
+44 (0)121 414 8480
Email
m.r.higgs@bham.ac.uk
View my research portal
Address
Institute of Cancer and Genomic Sciences: IBR West Extension
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Martin Higgs is a group leader in the Institute of Cancer and Genomic Sciences. He is currently Associate Professor for Genomics and Rare Disease, and leads a research group working on the cellular response to genotoxic stress. He is also Deputy Director for the Centre for Rare Disease Studies (CRDS) Birmingham.  

Martin’s area of expertise is the study of a single post-translational modification, known as Lysine methylation, and how this regulates the cellular response to DNA damage. In addition, part of his work focuses on the role of lysine methylation in ensuring human development and preventing rare human diseases. He has particular interests in studying neurodevelopmental disorders caused by mutations in the lysine methylation apparatus.

He also maintains a long-standing interest in the impact of chronic viral infection on lysine methylation and DNA repair, and on the consequences during tumourigenesis. 

He has published papers in top journals, such as Molecular Cell, Oncogene, Cancer Research and Nature Genetics, and has been invited to speak at both national and international conferences.

Qualifications

  • PG Certificate in HE, 2020
  • PhD in Virology, University of Glasgow, 2008
  • BSc in Molecular & Cellular Biology, University of Stirling, 2004

Biography

Martin graduated with a BSc from the University of Stirling in 2003. He then worked in Leeds with Professor Mark Harris on characterising the hepatitis C virus (HCV) protein p7, before moving to the (former) MRC Virology Unit in Glasgow to study for his PhD with Dr Nigel Stow. 

He then undertook post-doctoral research in the laboratory of Professor Jean-Michel Pawlotsky in Paris, France, on the impact of HCV on the cellular response to DNA damage and cellular signalling. 

In 2012, he moved to the University of Birmingham to join the group of Professor Grant Stewart, where he studied novel actors in the cellular response to replication stress. 

In 2016, he was awarded an MRC Career Development Fellowship and was appointed Birmingham Fellow in Genomics and Rare Disease and established his research group in 2017. He was promoted to Associate Professor in 2021.

Teaching

Teaching management

Teaching delivery

Postgraduate supervision

Martin’s interests are in the cellular response to DNA damage, and examining the role of lysine methylation in this process. He is also interested in examining the impact of mutations in lysine methylation pathways on human health.

Martin is currently supervising doctoral and master’s students in studying how lysine methylation regulates cancer therapeutic efficacy and DNA repair. Previous students have gone on to further academic study, careers in life sciences, or PhDs.

He is always interested in supervising keen and motivated individuals: if you are seeking a PhD position in the fields of DNA repair and/or human genetics, and have an excellent and competitive CV, then please contact him directly.

Research

Martin’s current research focuses around identifying how cells respond to and resolve DNA damage, particularly that arising during DNA replication. 

He is particularly interested in elucidating how protein Lysine methylation contributes to safeguarding genome stability, and in identifying novel factors involved in this response. He is also interested in elucidating how deficiencies in these pathways contribute to human disease. 

He also maintains a long-standing interest in the impact of chronic viral infection on this process, and on the consequences of this on the DNA damage response during carcinogenesis. 

For more details, please visit his lab page.

Current Projects

  • Assessing the impact of histone methylation on DNA repair and anti-cancer therapies
  • Investigating the role of lysine methyltransferases in maintaining genome stability
  • Uncovering new roles for non-histone methylation in DNA repair and replication
  • Profiling mutations in the lysine methylation apparatus and the impact on genomic stability
  • Investigating how genome instability contributes to rare diseases caused by mutations in lysine methyltransferases

Other activities

Reviewer for grant funding bodies and journals, including Nature Communications, Oncogene, Nucleic Acids Research, MRC, BBSRC and the NIH.

Publications

Highlight publications

The COMPLEXO Network 2020, 'Germline RBBP8 variants associated with early-onset breast cancer compromise replication fork stability', Journal of Clinical Investigation, vol. 130, no. 8, pp. 4069-4080. https://doi.org/10.1172/JCI127521

Kummerling, J, Stremmelaar, DE, Raun, N, Reijnders, MRF, Willemsen, MH, Ruiterkamp-Versteeg, M, Schepens, M, Man, CCO, Gilissen, C, Cho, MT, McWalter, K, Sinnema, M, Wheless, JW, Simon, MEH, Genetti, CA, Casey, AM, Terhal, PA, van der Smagt, JJ, van Gassen, KLI, Joset, P, Bahr, A, Steindl, K, Rauch, A, Keller, E, Raas-Rothschild, A, Koolen, DA, Agrawal, PB, Hoffman, TL, Powell-Hamilton, NN, Thiffault, I, Engleman, K, Zhou, D, Bodamer, O, Hoefele, J, Riedhammer, KM, Schwaibold, EMC, Tasic, V, Schubert, D, Top, D, Pfundt, R, Higgs, M, Kramer, JM & Kleefstra, T 2020, 'Characterization of SETD1A haploinsufficiency in humans and Drosophila defines a novel neurodevelopmental syndrome', Molecular Psychiatry. https://doi.org/10.1038/s41380-020-0725-5

Higgs, M, Sato, K, Reynolds, J, Begum, S, Bayley, R, Goula, A, Vernet, A, Paquin, K, Skalnik, D, Kobayashi, W, Takata, M, Howlett, N, Kurumizaka, H, Kimura, H & Stewart, G 2018, 'Histone methylation by SETD1A protects nascent DNA through the nucleosome chaperone activity of FANCD2', Molecular Cell, vol. 71, no. 1, pp. 25-41.e6. https://doi.org/10.1016/j.molcel.2018.05.018

Begum, S, Goula, A, Bayley, R & Higgs, M 2018, 'On your marks, get SET(D1A): the race to protect stalled replication forks', Molecular and Cellular Oncology, vol. 5, no. 6, e1511209. https://doi.org/10.1080/23723556.2018.1511209

Recent publications

Article

Bayley, R, Borel, V, Moss, R, Sweatman, E, Ruis, P, Ormrod, A, Goula, A, Mottram, R, Stanage, T, Hewitt, G, Saponaro, M, Stewart, G, Boulton, S & Higgs, M 2022, 'H3K4 methylation by SETD1A/BOD1L facilitates RIF1-dependent NHEJ', Molecular Cell, vol. 82, no. 10, pp. 1924-1939.e10. https://doi.org/10.1016/j.molcel.2022.03.030

Grange, LJ, Reynolds, JJ, Ullah, F, Isidor, B, Shearer, RF, Latypova, X, Baxley, RM, Oliver, AW, Ganesh, A, Cooke, SL, Jhujh, SS, McNee, GS, Hollingworth, R, Higgs, MR, Natsume, T, Khan, T, Martos-Moreno, GÁ, Chupp, S, Mathew, CG, Parry, D, Simpson, MA, Nahavandi, N, Yüksel, Z, Drasdo, M, Kron, A, Vogt, P, Jonasson, A, Seth, SA, Gonzaga-Jauregui, C, Brigatti, KW, Stegmann, APA, Kanemaki, M, Josifova, D, Uchiyama, Y, Oh, Y, Morimoto, A, Osaka, H, Ammous, Z, Argente, J, Matsumoto, N, Stumpel, CTRM, Taylor, AMR, Jackson, AP, Bielinsky, A-K, Mailand, N, Le Caignec, C, Davis, EE & Stewart, GS 2022, 'Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy', Nature Communications, vol. 13, no. 1, 6664. https://doi.org/10.1038/s41467-022-34349-8

Wang, J, Rojas, P, Mao, J, Muste Sadurni, M, Garnier, O, Xiao, S, Higgs, M, Garcia, P & Saponaro, M 2021, 'Persistence of RNA transcription during DNA replication delays duplication of transcription start sites until G2/M', Cell Reports, vol. 34, no. 7, 108759. https://doi.org/10.1016/j.celrep.2021.108759

Wing, P, Davenne, T, Wettengel, J, Lai, AG, Zhuang, X, Chakraborty, A, d'Arienzo, V, Kramer, C, Ko, C, Harris, J, Schreiner, S, Higgs, M, Roessler, S, Parish, J, Protzer, U, Balfe, P, Rehwinkel, J & McKeating, JA 2019, 'A dual role for SAMHD1 in regulating HBV cccDNA and RT-dependent particle genesis', Life Science Alliance, vol. 2, no. 2. https://doi.org/10.26508/lsa.201900355

Burrage, L, Reynolds, J, Baratang, N, Phillips, J, Wegner, J, McFarquhar, A, Higgs, M, Christiansen, A, Lanza, D, Seavitt, J, Jain, M, Li, X, Parry, D, Raman, V, Chitayat, D, Chinn, I, Bertuch, A, Karaviti, L, Schlesinger, A, Earl, D, Bamshad, M, Savarirayan, R, Doddapaneni, H, Muzny, D, Jhangiani, S, Eng, C, Gibbs, R, Bi, W, Emrick, L, Rosenfeld, J, Postlethwait, J, Westerfield, M, Dickinson, M, Beaudet, A, Ranza, E, Huber, C, Cormier-Daire, V, Shen, W, Mao, R, Heaney, J, Orange, J, Undiagnosed Diseases Network, Bertola, D, Yamamoto, G, Baratela, W, Butler, M, Ali, A, Adeli, M, Cohn, D, Krakow, D, Jackson, A, Lees, M, Offiah, A, Carlston, C, Carey, J, Stewart, G, Bacino, C, Campeau, P & Lee, B 2019, 'Biallelic Variants in TONSL Cause SPONASTRIME Dysplasia and a Spectrum of Skeletal Dysplasia Phenotypes', American Journal of Human Genetics, vol. 104, no. 3, pp. 422-438. https://doi.org/10.1016/j.ajhg.2019.01.007

Chang, HR, Cho, SY, Lee, JH, Lee, E, Soo, J, Lee, HR, Cavalcanti, DP, Mäkitie, O, Valta, H, Girisha, KM, Lee, C, Neethukrishna, K, Bhavani, GS, Shukla, A, Nampoothiri, S, Phadke, SR, Park, MJ, Ikegawa, S, Wang, Z, Higgs, M, Stewart, G, Jung, E, Lee, M-S, Park, JH, Lee, EA, Kim, H, Myung, K, Jeon, W, Lee, K, Kim, D, Kim, O-H, Choi, M, Lee, H-W, Kim, Y & Cho, T-J 2019, 'Hypomorphic Mutations in TONSL Cause SPONASTRIME Dysplasia', American Journal of Human Genetics, vol. 104, no. 3, pp. 439-453. https://doi.org/10.1016/j.ajhg.2019.01.009

Bayley, R, Blakemore, D, Cancian, L, Dumon, S, Volpe, G, Ward, C, Al Maghrabi, R, Gujar, J, Reeve, N, Raghavan, M, Higgs, M, Stewart, G, Petermann, E & Garcia, P 2018, 'MYBL2 supports DNA double strand break repair in haematopoietic stem cells', Cancer Research, vol. 78, no. 20, pp. 5767-5779. https://doi.org/10.1158/0008-5472.CAN-18-0273, https://doi.org/10.1158/0008-5472.can-18-0273

Ronson, G, Piberger, AL, Higgs, M, Olsen, A, Stewart, G, McHugh, P, Petermann, E & Lakin, N 2018, 'PARP1 and PARP2 stabilise replication forks at base excision repair intermediates through Fbh1-dependent Rad51 regulation', Nature Communications, vol. 9, no. 1, 746. https://doi.org/10.1038/s41467-018-03159-2

Marsh, E, Delury, C, Davies, N, Weston, C, Miah, MAL, Banks, L, Parish, J, Higgs, M & Roberts, S 2017, 'Mitotic control of human papillomavirus genome-containing cells is regulated by the function of the PDZ-binding motif of the E6 oncoprotein', OncoTarget, vol. 8, pp. 19491-19506. https://doi.org/10.18632/oncotarget.14469

Reynolds, J, Higgs, M, Zlatanou, A, Vernet, A, Mottram, R, Brean, A, Taylor, M, Alkuraya, FS, Mathew, CG, Jackson, AP & Stewart, G 2017, 'Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism', Nature Genetics, vol. 49, pp. 537–549. https://doi.org/10.1038/ng.3790

Higgs, M & Stewart, G 2016, 'Protection or resection: BOD1L as a novel replication fork protection factor', Nucleus (Austin). https://doi.org/10.1080/19491034.2016.1143183

Harley, ME, Murina, O, Leitch, A, Higgs, M, Bicknell, LS, Yigit, G, Blackford, AN, Zlatanou, A, Mackenzie, KJ, Reddy, K, Halachev, M, McGlasson, S, Reijns, MAM, Fluteau, A, Martin, C-A, Sabbioneda, S, Elcioglu, NH, Altmüller, J, Thiele, H, Greenhalgh, L, Chessa, L, Maghnie, M, Salim, M, Bober, MB, Nürnberg, P, Jackson, SP, Hurles, ME, Wollnik, B, Stewart, G & Jackson, A 2016, 'TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism', Nature Genetics, vol. 48, no. 1, pp. 36-43. https://doi.org/10.1038/ng.3451

Higgs, M, Reynolds, J, Winczura, A, Blackford, AN, Borel, V, Miller, E, Zlatanou, A, Nieminuszczy, J, Ryan, E, Davies, N, Stankovic, T, Boulton, S, Niedzwiedz, W & Stewart, G 2015, 'Bod1l is required to suppress deleterious resection of stressed replication forks', Molecular Cell, vol. 59, no. 3, pp. 462-477. https://doi.org/10.1016/j.molcel.2015.06.007

Chapter (peer-reviewed)

Kotsantis, P, Jones, R, Higgs, M & Petermann, E 2015, Cancer Therapy and Replication Stress: Forks on the Road to Perdition. in GS Makowski (ed.), Advances in Clinical Chemistry. vol. 69, Academic Press (Elsevier), pp. 91-138. <http://www.sciencedirect.com/science/article/pii/S0065242314000420>

Preprint

Mahony, CB, Noyvert, B, Vrljicak, P, Ott, S, Higgs, M & Monteiro, R 2021 'Gata2a maintains cebpa and npm1a in haematopoietic stem cells to sustain lineage differentiation and genome stability' bioRxiv. https://doi.org/10.1101/2021.07.19.452890

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