Mitochondrial Oncogenetics
Group Leader:
Prof Payam Gammage
Mutations of mitochondrial DNA (mtDNA) are among the most common genetic events in all cancer, however their impact on disease initiation and progression is not understood. Mitochondria perform numerous metabolic functions, relying on faithful expression and maintenance of mtDNA, a small, multi-copy genome separate from the nuclear DNA that is contained exclusively within mitochondria. Mutations of mtDNA and gross changes to mtDNA copy number can lead to profound metabolic alterations – one of the earliest identified hallmarks of cancer – and these changes are observed in >60% of tumours.
To understand the relationship between mitochondrial genetics and metabolic dysfunction in cancer, our lab studies a range of cancer models using genetic and metabolic analyses alongside the development and enhancement of mitochondrial genome engineering tools and model systems. By better understanding the relationship between mtDNA mutation and cancer we are developing new therapeutic targets and approaches for clinical application, including the informed reallocation of existing treatments based on mtDNA genotype.
Lab Reports
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Recent Publications
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Lab Members
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Recent Publications
2026
MacVicar T, Greaves LC, Gammage PA, Tait SWG, Fisher-Wellman KH, Freedman G. Cancer as a window into mitochondrial biology. Cell Metab. 2026(6):1085-1088.
2025
Boscenco S, Tait-Mulder J, Kim M, Tang C, Park T, McNulty F, Lilla S, Zanivan S, Huerta-Uribe A, Nalbant B, Zucker M, Sumpton D, Monteuuis G, Jackson CB, Wei W, Chinnery PF, Chaligne R, Lareau CA, Reznik E, Gammage PA. Functionally dominant hotspot mutations of mitochondrial ribosomal RNA genes in cancer. Nature Genetics. 2025.
Nash PA, Turner KM, Powell CA, Van Haute L, Silva-Pinheiro P, Bubeck F, Wiedtke E, Marques E, Ryan DG, Grimm D, Gammage PA, Minczuk M. Clinically translatable mitochondrial gene therapy in muscle using tandem mtZFN architecture. EMBO Mol Med. 2025.
Novak J, Nahacka Z, Oliveira GL, Brisudova P, Dubisova M, Dvorakova S, Miklovicova S, Dalecka M, Puttrich V, Grycova L, Magalhaes-Novais S, Correia CM, Levoux J, Stepanek L, Prochazka J, Svec D, Reguera DP, Lopez-Domenech G, Zobalova R, Sedlacek R, Terp MG, Gammage PA, Lansky Z, Kittler J, Oliveira PJ, Ditzel HJ, Berridge MV, Rodriguez AM, Boukalova S, Rohlena J, Neuzil J. The adaptor protein Miro1 modulates horizontal transfer of mitochondria in mouse melanoma models. Cell Rep. 2025;44(1):115154.
Samarakoon Y, Yelland T, Garcia-Gonzalez E, da Silva Justo Junior A, Mahmood M, Manoharan A, Patterson S, Serafin V, Gammage PA, Marmiroli S, Halsey C, Ismail S, Roberts EW. UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia. Life Sci Alliance. 2025;8(3).
2024
Kim M, Gorelick AN, Vàzquez-García I, Williams MJ, Salehi S, Shi H, Weiner AC, Ceglia N, Funnell T, Park T, Boscenco S, O’Flanagan CH, Jiang H, Grewal D, Tang C, Rusk N, Gammage PA, McPherson A, Aparicio S, Shah SP, Reznik E. Single-cell mtDNA dynamics in tumors is driven by coregulation of nuclear and mitochondrial genomes. Nature Genetics. 2024.
Mahmood M, Liu EM, Shergold AL, Tolla E, Tait-Mulder J, Huerta-Uribe A, Shokry E, Young AL, Lilla S, Kim M, Park T, Boscenco S, Manchon JL, Rodríguez-Antona C, Walters RC, Springett RJ, Blaza JN, Mitchell L, Blyth K, Zanivan S, Sumpton D, Roberts EW, Reznik E, Gammage PA. Mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade response in melanoma. Nat Cancer. 2024.
2023
Mahmood M, Liu EM, Shergold AL, Tolla E, Tait-Mulder J, Uribe AH, Shokry E, Young AL, Lilla S, Kim M, Park T, Manchon JL, Rodriguez-Antona C, Walters RC, Springett RJ, Blaza JN, Zanivan S, Sumpton DA, Roberts EW, Reznik E, Gammage PA. Tumour mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade. bioRxiv. 2023;Volume:2023.2003.2021.533091.
Shaw AM, Gammage PA. Coupling Differential Centrifugation with Exonuclease Treatment and Size Exclusion Chromatography (DIFSEC) for Purification of mtDNA from Mammalian Cells. Methods Mol Biol. 2023;2615:31-40.
2022
Ganly I, Liu EM, Kuo F, Makarov V, Dong Y, Park J, Gong Y, Gorelick AN, Knauf JA, Benedetti E, Tait-Mulder J, Morris LGT, Fagin JA, Intelkofer AM, Krumsiek J, Gammage P, Ghossein R, Xu B, Chan TA, Reznik E. Mitonuclear genotype remodels the metabolic and microenvironmental landscape of Hürthle cell carcinoma. Sci Adv. 2022;8(25):eabn9699.
Kim M, Mahmood M, Reznik E, Gammage PA. Mitochondrial DNA is a major source of driver mutations in cancer. Trends in Cancer. 2022;8:1046-1059
2021
Gorelick AN, Kim M, Chatila WK, La K, Hakimi AA, Berger MF, Taylor BS, Gammage PA, Reznik E. Respiratory complex and tissue lineage drive recurrent mutations in tumour mtDNA. Nat Metab. 2021; 3:558–570
See the following articles for insights into this study: Mutations in overlooked DNA could have profound impact on bowel cancer survival and Mitochondrial DNA in cancer: small genome, big impact
Rabas N, Palmer S, Mitchell L, Ismail S, Gohlke A, Riley JS, Tait SWG, Gammage P, Soares LL, Macpherson IR, Norman JC. PINK1 drives production of mtDNA-containing extracellular vesicles to promote invasiveness. J Cell Biol. 2021;220.
2020
Bacman SR, Gammage PA, Minczuk M, Moraes CT. Manipulation of mitochondrial genes and mtDNA heteroplasmy. Methods in cell biology. 2020;155:441-487.
Jackson CB, Turnbull DM, Minczuk M, Gammage PA. Therapeutic Manipulation of mtDNA Heteroplasmy: A Shifting Perspective. Trends in Molecular Medicine. 2020; 26: 698-709
Pinheiro P, A. Gammage P, Minczuk M. Chapter 19 – Mitochondrially targeted zinc finger nucleases. In: Gasparre G, Porcelli AM, eds. The Human Mitochondrial Genome. Academic Press; 2020:499-514.
2019
Andreazza S, Samstag CL, Sanchez-Martinez A, Fernandez-Vizarra E, Gomez-Duran A, Lee JJ, Tufi R, Hipp MJ, Schmidt EK, Nicholls TJ, Gammage PA, Chinnery PF, Minczuk M, Pallanck LJ, Kennedy SR, Whitworth AJ. Mitochondrially-targeted APOBEC1 is a potent mtDNA mutator affecting mitochondrial function and organismal fitness in Drosophila. Nature communications. 2019;10:3280.
Gammage PA, Frezza C. Mitochondrial DNA: the overlooked oncogenome? BMC biology. 2019;17:53. 
Hoitzing H, Gammage PA, Haute LV, Minczuk M, Johnston IG, Jones NS. Energetic costs of cellular and therapeutic control of stochastic mitochondrial DNA populations. PLoS computational biology. 2019;15:e1007023.
2018
Gammage PA, Minczuk M. Enhanced Manipulation of Human Mitochondrial DNA Heteroplasmy In Vitro Using Tunable mtZFN Technology. Methods in molecular biology (Clifton, NJ). 2018;1867:43-56.
Gammage PA, Moraes CT, Minczuk M. Mitochondrial Genome Engineering: The Revolution May Not Be CRISPR-Ized. Trends in genetics : TIG. 2018;34:101-110.
Gammage PA, Viscomi C, Simard ML, Costa ASH, Gaude E, Powell CA, Van Haute L, McCann BJ, Rebelo-Guiomar P, Cerutti R, Zhang L, Rebar EJ, Zeviani M, Frezza C, Stewart JB, Minczuk M. Genome editing in mitochondria corrects a pathogenic mtDNA mutation in vivo. Nature medicine. 2018;24:1691-1695.
Gaude E, Schmidt C, Gammage PA, Dugourd A, Blacker T, Chew SP, Saez-Rodriguez J, O’Neill JS, Szabadkai G, Minczuk M, Frezza C. NADH Shuttling Couples Cytosolic Reductive Carboxylation of Glutamine with Glycolysis in Cells with Mitochondrial Dysfunction. Molecular cell. 2018;69:581-593.e587
Kullar PJ, Gomez-Duran A, Gammage PA, Garone C, Minczuk M, Golder Z, Wilson J, Montoya J, Hakli S, Karppa M, Horvath R, Majamaa K, Chinnery PF. Heterozygous SSBP1 start loss mutation co-segregates with hearing loss and the m.1555A>G mtDNA variant in a large multigenerational family. Brain : a journal of neurology. 2018;141:55-62
McCann BJ, Cox A, Gammage PA, Stewart JB, Zernicka-Goetz M, Minczuk M. Delivery of mtZFNs into Early Mouse Embryos. Methods in molecular biology. 2018;1867:215-228.
Peeva V, Blei D, Trombly G, Corsi S, Szukszto MJ, Rebelo-Guiomar P, Gammage PA, Kudin AP, Becker C, Altmuller J, Minczuk M, Zsurka G, Kunz WS. Linear mitochondrial DNA is rapidly degraded by components of the replication machinery. Nature communications. 2018;9:1727.
2016
Gammage PA, Gaude E, Van Haute L, Rebelo-Guiomar P, Jackson CB, Rorbach J, Pekalski ML, Robinson AJ, Charpentier M, Concordet JP, Frezza C, Minczuk M. Near-complete elimination of mutant mtDNA by iterative or dynamic dose-controlled treatment with mtZFNs. Nucleic acids research. 2016;44:7804-7816.
Gammage PA, Van Haute L, Minczuk M. Engineered mtZFNs for Manipulation of Human Mitochondrial DNA Heteroplasmy. Methods in molecular biology (Clifton, NJ). 2016;1351:145-162.
Research Scientist
Fergus Bremner*
Information about this team member’s research interests, experience, and background will be added soon. Please check back for updates.
Research Scientist
Peggy Paschke
I am originally from Germany where I did my undergraduates and PhD. I joined the CRUK SI in 2019 and had several different roles since then. In my current position in the Bryant lab, I try to establish efficient organoid engineering using CRISPR. In the lab I enjoy doing microscopy, image processing, image analysis as well as doing molecular biology and cloning. In my free time I like to go running, hiking, hanging out with my naughty felines and watching movies.
Research Scientist
Elisabetta Tolla
I am a postdoctoral researcher in the lab, investigating the role of mitochondrial DNA mutations in colorectal cancer by using different types of cancer models. I am specifically interested in how mitochondrial DNA mutations alter metabolic pathways in the cells and whether these affect colorectal cancer initiation, progression and metastasis. Before joining the CRUK Scotland Institute, I completed my PhD at the University of Glasgow studying neuroendocrine and epigenetic mechanisms underlying circannual reproductive rhythms in mammals and birds. Outside of the lab, I enjoy travelling, taking part in musicals and getting out in nature.
Scientific Officer
Jacqueline Tait-Mulder
I did my Ph.D. at the Netherlands Cancer Institute and post-doc at the St Jude Children’s Research Hospital, Memphis, USA. We then moved to Scotland and after the birth of my third child, I started working at the CRUK Scotland Institute. Since then, I have been supporting and working in several groups, becoming a Senior Scientific Officer and now a Principal Scientific Officer in the lab of Payam Gammage working on mitochondrial DNA mutations in cancer. My experience is widespread, having worked in several labs, institutes, and scientific areas. I enjoy the continuous excitement of scientific discoveries, and I enjoy helping others wherever I can. In my free time I like to garden, spend time with friends, play games with my family and walk our dog.
Scientific Officer
Zaniah Gonzalez
I am a Senior Scientific Officer with a background in stem cell biology, development, and the role of mitochondrial mutations in cancer. I completed my PhD in Regenerative Medicine at the University of Edinburgh and held several postdoctoral positions before joining the Greaves group -which operates as the sister lab to the Newcastle lab in Glasgow— to help steer our research forward. My role blends senior technical and operational leadership—keeping everything running smoothly, setting up reproducible protocols, and managing the day-to-day coordination across our Glasgow and Newcastle sites.
I work with a high degree of independence to support both our immediate projects and long-term planning, which currently includes driving critical data collection for our MRC programme application and helping lay the groundwork for a future Centre of Research Excellence. I love using my varied technical background to help team members design and execute their experiments, ensuring our science is as impactful as possible.
Outside of the lab, I'm happiest spending quality time with my family, getting out into nature, cycling, or settling down with a great Sci-Fi book.
Scientific Officer
Hannah Mearns*
Information about this team member’s research interests, experience, and background will be added soon. Please check back for updates.
Graduate Student
Flora McNulty
I am a PhD student from Glasgow, Scotland. I completed my undergraduate degree in Genetics at the University of Glasgow. I am going into my third year in the Gammage lab, where my project aims on understanding regulators of mitochondrial DNA copy number in Cancer. Outside of the lab I enjoy running, cooking and keeping up to date with films.
Graduate Student
Amy Shepherd*
Information about this team member’s research interests, experience, and background will be added soon. Please check back for updates.