Mathew Garnett

Wellcome Sanger Institute

Biography

Dr Mathew Garnett has dedicated his career to unravelling the complexities of cancer biology and translating these findings into new cancer treatments. Notable achievements in his early career include contributing to the identification of the BRAF cancer gene and advancing our knowledge of RAF regulation with implications for targeted BRAF cancer drugs. Additionally, he uncovered UBE2S’s role in regulating cell division and influencing responses to anti-mitotic cancer drugs.

At the forefront of using CRISPR gene-editing, Dr Garnett’s research has uncovered insights into gene function. A key discovery was the identification of Werner syndrome helicase as a target in cancers with microsatellite instability, leading to the clinical development of WRN inhibitors and new insights into DNA mismatch repair machinery.

Dr Garnett’s laboratory has pioneered systematic drug and CRISPR screens in genomically-annotated cell models, identifying treatment response biomarkers and new drug targets. He co-leads the Cancer Dependency Map, which aims to systematically identify vulnerabilities in cancer cells to guide precision medicines. The reference datasets produced have directly contributed to drug discovery programmes and are shared through leading online portals, including the Cell Model Passports and Genomics of Drug Sensitivity hosted by his laboratory, influencing hundreds of publications.

His team demonstrated the feasibility of creating a biobank of human tumour organoids and have contributed hundreds of organoid models to the international Human Cancer Model Initiative (HCMI) as a community resource.

As a founder of Mosaic Therapeutics, and through industry collaboration, Dr Garnett plays a role in using genomics to develop cancer drugs. Together, Dr Garnett’s scientific discoveries are leading to clinical innovations directly informing personalised treatment of cancer.

Relevant Publications

Base editing screens define the genetic landscape of cancer drug resistance mechanisms

Coelho M.A., Strauss M.E., Watterson A., Cooper S., Bhosle S., Illuzzi G., Karakoc E., Dinçer C., Vieira S.F., Sharma M., Moullet M., Conticelli D., Koeppel J., McCarten K., Cattaneo C.M., Veninga V., Picco G., Parts L., Forment J.V., Voest E.E., Marioni J.C., Bassett A., Garnett M.J., Nature Genetics (2024).

10.1038/s41588-024-01948-8
A comprehensive clinically informed map of dependencies in cancer cells and framework for target prioritization

Pacini C., Duncan E., Gonçalves E., Gilbert J., Bhosle S., Horswell S., Karakoc E., Lightfoot H., Curry E., Muyas F., Bouaboula M., Pedamallu C.S., Cortes-Ciriano I., Behan F.M., Zalmas L.P., Barthorpe A., Francies H., Rowley S., Pollard J., Beltrao P., Parts L., Iorio F., Garnett M.J., Cancer Cell (2024).

10.1016/j.ccell.2023.12.016
Effective drug combinations in breast, colon and pancreatic cancer cells

Jaaks P., Coker E.A., Vis D.J., Edwards O., Carpenter E.F., Leto S.M., Dwane L., Sassi F., Lightfoot H., Barthorpe S., van der Meer D., Yang W., Beck A., Mironenko T., Hall C., Hall J., Mali I., Richardson L., Tolley C., Morris J., Thomas F., Lleshi E., Aben N., Benes C.H., Bertotti A., Trusolino L., Wessels L., Garnett M.J., Nature (2022).

10.1038/s41586-022-04437-2
Minimal genome-wide human CRISPR-Cas9 library

Gonçalves E., Thomas M., Behan F.M., Picco G., Pacini C., Allen F., Vinceti A., Sharma M., Jackson D.A., Price S., Beaver C.M., Dovey O., Parry-Smith D., Iorio F., Parts L., Yusa K., Garnett M.J., Genome Biology (2021).

10.1186/s13059-021-02268-4
Prioritization of cancer therapeutic targets using CRISPR-Cas9 screens

Behan F.M., Iorio F., Picco G., Gonçalves E., Beaver C.M., Migliardi G., Santos R., Rao Y., Sassi F., Pinnelli M., Ansari R., Harper S., Jackson D.A., McRae R., Pooley R., Wilkinson P., van der Meer D., Dow D., Buser-Doepner C., Bertotti A., Trusolino L., Stronach E.A., Saez-Rodriguez J., Yusa K., Garnett M.J., Nature (2019).

10.1038/s41586-019-1103-9
Cell Model Passports-a hub for clinical, genetic and functional datasets of preclinical cancer models

van der Meer D., Barthorpe S., Yang W., Lightfoot H., Hall C., Gilbert J., Francies H.E., Garnett M.J., Nucleic Acids Research (2018).

10.1093/nar/gky872
A Landscape of Pharmacogenomic Interactions in Cancer

Iorio F., Knijnenburg T.A., Vis D.J., Bignell G.R., Menden M.P., Schubert M., Aben N., Gonçalves E., Barthorpe S., Lightfoot H., Cokelaer T., Greninger P., van Dyk E., Chang H., de Silva H., Heyn H., Deng X., Egan R.K., Liu Q., Mironenko T., Mitropoulos X., Richardson L., Wang J., Zhang T., Moran S., Sayols S., Soleimani M., Tamborero D., Lopez-Bigas N., Ross-Macdonald P., Esteller M., Gray N.S., Haber D.A., Stratton M.R., Benes C.H., Wessels L.F., Saez-Rodriguez J., McDermott U., Garnett M.J., Cell (2016).

10.1016/j.cell.2016.06.017
Prospective derivation of a living organoid biobank of colorectal cancer patients

van de Wetering M., Francies H.E., Francis J.M., Bounova G., Iorio F., Pronk A., van Houdt W., van Gorp J., Taylor-Weiner A., Kester L., McLaren-Douglas A., Blokker J., Jaksani S., Bartfeld S., Volckman R., van Sluis P., Li V.S., Seepo S., Pedamallu C.S., Cibulskis K., Carter S.L., McKenna A., Lawrence M.S., Lichtenstein L., Stewart C., Koster J., Versteeg R., van Oudenaarden A., Saez-Rodriguez J., Vries R.G., Getz G., Wessels L., Stratton M.R., McDermott U., Meyerson M., Garnett M.J., Clevers H., Cell (2015).

10.1016/j.cell.2015.03.053
Genomics of Drug Sensitivity in Cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells

Yang W., Soares J., Greninger P., Edelman E.J., Lightfoot H., Forbes S., Bindal N., Beare D., Smith J.A., Thompson I.R., Ramaswamy S., Futreal P.A., Haber D.A., Stratton M.R., Benes C.H., McDermott U., Garnett M.J., Nucleic Acids Research (2013).

10.1093/nar/gks1111