Garnett Group | Translational Cancer Genomics

Garnett Group | Translational Cancer Genomics

Garnett Group

Garnett GroupSanger Institute, Genome Research Limited
Garnett Group

Our Research and Approach

We investigate how abnormalities in the DNA of cells contribute to cancer and impact on patient responses to therapy. This provides fundamental insights into disease mechanisms with implications for the development of improved therapies.

There are currently four complementary research focuses in my laboratory:

  • The genomics of drug sensitivity. High-throughput drug screens in human cancer cell cultures to identify genetic features of cancer cells that are predictive of drug sensitivity.
  • Mapping synthetic-lethal dependencies in cancer cells. Genome-wide CRISPR-Cas9 synthetic-lethal screens in cancer cell lines to identify potential new oncology drug targets. 
  • A new generation of organoid cancer models. Methods for the derivation and characterisation of a new set of cancer organoid in vitro cell culture models.
  • Precision organoid models to study cancer gene function.  Genome-editing to introduce specific genetic alterations into healthy and cancer organoids to study their function. 

To find out more indepth information please click on the read more button.

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People

Garnett, Mathew
Dr Mathew Garnett, PhD
Group Leader

Mathew leads the Translational Cancer Genomics team. 

Mathew has a long-standing research interest in understanding how genetic changes which occur in cancer cells can be exploited to develop targeted cancer therapies.

His background is in molecular cell biology, high-throughput chemical and genetic screens, cancer genomics and anti-cancer therapeutics.

Key Projects, Collaborations, Tools & Data

Our group is involved in the generation of a number of datasets and web tools which are used by the scientific community.

Research Programmes

Partners and Funders

Internal Partners

Publications

  • A Landscape of Pharmacogenomic Interactions in Cancer.

    Iorio F, Knijnenburg TA, Vis DJ, Bignell GR, Menden MP et al.

    Cell 2016;166;3;740-54

  • Combinations of PARP Inhibitors with Temozolomide Drive PARP1 Trapping and Apoptosis in Ewing's Sarcoma.

    Gill SJ, Travers J, Pshenichnaya I, Kogera FA, Barthorpe S et al.

    PloS one 2015;10;10;e0140988

  • Prospective derivation of a living organoid biobank of colorectal cancer patients.

    van de Wetering M, Francies HE, Francis JM, Bounova G, Iorio F et al.

    Cell 2015;161;4;933-45

  • Genomics of Drug Sensitivity in Cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells.

    Yang W, Soares J, Greninger P, Edelman EJ, Lightfoot H et al.

    Nucleic acids research 2013;41;Database issue;D955-61

  • Systematic identification of genomic markers of drug sensitivity in cancer cells.

    Garnett MJ, Edelman EJ, Heidorn SJ, Greenman CD, Dastur A et al.

    Nature 2012;483;7391;570-5

  • UBE2S elongates ubiquitin chains on APC/C substrates to promote mitotic exit.

    Garnett MJ, Mansfeld J, Godwin C, Matsusaka T, Wu J et al.

    Nature cell biology 2009;11;11;1363-9

  • Wild-type and mutant B-RAF activate C-RAF through distinct mechanisms involving heterodimerization.

    Garnett MJ, Rana S, Paterson H, Barford D and Marais R

    Molecular cell 2005;20;6;963-9

  • Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF.

    Wan PT, Garnett MJ, Roe SM, Lee S, Niculescu-Duvaz D et al.

    Cell 2004;116;6;855-67

  • A Road Map for Precision Cancer Medicine Using Personalized Models.

    Picco G and Garnett MJ

    Cancer discovery 2017;7;5;456-458

  • Drug resistance mechanisms in colorectal cancer dissected with cell type-specific dynamic logic models.

    Eduati F, Doldàn-Martelli V, Klinger B, Cokelaer T, Sieber A et al.

    Cancer research 2017

  • Genome-wide chemical mutagenesis screens allow unbiased saturation of the cancer genome and identification of drug resistance mutations.

    Brammeld JS, Petljak M, Martincorena I, Williams SP, Alonso LG et al.

    Genome research 2017;27;4;613-625

  • Revisiting olfactory receptors as putative drivers of cancer.

    Ranzani M, Iyer V, Ibarra-Soria X, Del Castillo Velasco-Herrera M, Garnett M et al.

    Wellcome open research 2017;2;9

  • Logic models to predict continuous outputs based on binary inputs with an application to personalized cancer therapy.

    Knijnenburg TA, Klau GW, Iorio F, Garnett MJ, McDermott U et al.

    Scientific reports 2016;6;36812

  • Drug Sensitivity Assays of Human Cancer Organoid Cultures.

    Francies HE, Barthorpe A, McLaren-Douglas A, Barendt WJ and Garnett MJ

    Methods in molecular biology (Clifton, N.J.) 2016

  • A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds.

    Bruna A, Rueda OM, Greenwood W, Batra AS, Callari M et al.

    Cell 2016

  • A Landscape of Pharmacogenomic Interactions in Cancer.

    Iorio F, Knijnenburg TA, Vis DJ, Bignell GR, Menden MP et al.

    Cell 2016;166;3;740-54

  • Isocitrate dehydrogenase mutations confer dasatinib hypersensitivity and SRC-dependence in intrahepatic cholangiocarcinoma.

    Saha SK, Gordan JD, Kleinstiver BP, Vu P, Najem MS et al.

    Cancer discovery 2016

  • Multilevel models improve precision and speed of IC50 estimates.

    Vis DJ, Bombardelli L, Lightfoot H, Iorio F, Garnett MJ and Wessels LF

    Pharmacogenomics 2016

  • Exploitation of the Apoptosis-Primed State of MYCN-Amplified Neuroblastoma to Develop a Potent and Specific Targeted Therapy Combination.

    Ham J, Costa C, Sano R, Lochmann TL, Sennott EM et al.

    Cancer cell 2016;29;2;159-72

  • Pharmacogenomic agreement between two cancer cell line data sets.

    Cancer Cell Line Encyclopedia Consortium and Genomics of Drug Sensitivity in Cancer Consortium

    Nature 2015;528;7580;84-7

  • LIM kinase inhibitors disrupt mitotic microtubule organization and impair tumor cell proliferation.

    Mardilovich K, Baugh M, Crighton D, Kowalczyk D, Gabrielsen M et al.

    Oncotarget 2015;6;36;38469-86

  • Potent organo-osmium compound shifts metabolism in epithelial ovarian cancer cells.

    Hearn JM, Romero-Canelón I, Munro AF, Fu Y, Pizarro AM et al.

    Proceedings of the National Academy of Sciences of the United States of America 2015;112;29;E3800-5

  • Prospective derivation of a living organoid biobank of colorectal cancer patients.

    van de Wetering M, Francies HE, Francis JM, Bounova G, Iorio F et al.

    Cell 2015;161;4;933-45

  • BRAF/NRAS wild-type melanoma, NF1 status and sensitivity to trametinib.

    Ranzani M, Alifrangis C, Perna D, Dutton-Regester K, Pritchard A et al.

    Pigment cell & melanoma research 2015;28;1;117-9

  • Combinations of PARP Inhibitors with Temozolomide Drive PARP1 Trapping and Apoptosis in Ewing's Sarcoma.

    Gill SJ, Travers J, Pshenichnaya I, Kogera FA, Barthorpe S et al.

    PloS one 2015;10;10;e0140988

  • What role could organoids play in the personalization of cancer treatment?

    Francies HE and Garnett MJ

    Pharmacogenomics 2015;16;14;1523-6

  • Fast randomization of large genomic datasets while preserving alteration counts.

    Gobbi A, Iorio F, Dawson KJ, Wedge DC, Tamborero D et al.

    Bioinformatics (Oxford, England) 2014;30;17;i617-23

  • The evolving role of cancer cell line-based screens to define the impact of cancer genomes on drug response.

    Garnett MJ and McDermott U

    Current opinion in genetics & development 2014;24;114-9

  • Mcl-1 and FBW7 control a dominant survival pathway underlying HDAC and Bcl-2 inhibitor synergy in squamous cell carcinoma.

    He L, Torres-Lockhart K, Forster N, Ramakrishnan S, Greninger P et al.

    Cancer discovery 2013;3;3;324-37

  • Targeting MYCN in neuroblastoma by BET bromodomain inhibition.

    Puissant A, Frumm SM, Alexe G, Bassil CF, Qi J et al.

    Cancer discovery 2013;3;3;308-23

  • VS-5584, a novel and highly selective PI3K/mTOR kinase inhibitor for the treatment of cancer.

    Hart S, Novotny-Diermayr V, Goh KC, Williams M, Tan YC et al.

    Molecular cancer therapeutics 2013;12;2;151-61

  • Genomics of Drug Sensitivity in Cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells.

    Yang W, Soares J, Greninger P, Edelman EJ, Lightfoot H et al.

    Nucleic acids research 2013;41;Database issue;D955-61

  • MED12 controls the response to multiple cancer drugs through regulation of TGF-β receptor signaling.

    Huang S, Hölzel M, Knijnenburg T, Schlicker A, Roepman P et al.

    Cell 2012;151;5;937-50

  • Systematic identification of genomic markers of drug sensitivity in cancer cells.

    Garnett MJ, Edelman EJ, Heidorn SJ, Greenman CD, Dastur A et al.

    Nature 2012;483;7391;570-5

  • Exploiting genetic complexity in cancer to improve therapeutic strategies.

    Garnett MJ and McDermott U

    Drug discovery today 2012;17;5-6;188-93

  • A mitotic function for the high-mobility group protein HMG20b regulated by its interaction with the BRC repeats of the BRCA2 tumor suppressor.

    Lee M, Daniels MJ, Garnett MJ and Venkitaraman AR

    Oncogene 2011;30;30;3360-9

  • UBE2S elongates ubiquitin chains on APC/C substrates to promote mitotic exit.

    Garnett MJ, Mansfeld J, Godwin C, Matsusaka T, Wu J et al.

    Nature cell biology 2009;11;11;1363-9

  • Wild-type and mutant B-RAF activate C-RAF through distinct mechanisms involving heterodimerization.

    Garnett MJ, Rana S, Paterson H, Barford D and Marais R

    Molecular cell 2005;20;6;963-9

  • Mutations of C-RAF are rare in human cancer because C-RAF has a low basal kinase activity compared with B-RAF.

    Emuss V, Garnett M, Mason C and Marais R

    Cancer research 2005;65;21;9719-26

  • Guilty as charged: B-RAF is a human oncogene.

    Garnett MJ and Marais R

    Cancer cell 2004;6;4;313-9

  • Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF.

    Wan PT, Garnett MJ, Roe SM, Lee S, Niculescu-Duvaz D et al.

    Cell 2004;116;6;855-67

  • ETV6-NTRK3 transformation requires insulin-like growth factor 1 receptor signaling and is associated with constitutive IRS-1 tyrosine phosphorylation.

    Morrison KB, Tognon CE, Garnett MJ, Deal C and Sorensen PH

    Oncogene 2002;21;37;5684-95

  • Mutations of the BRAF gene in human cancer.

    Davies H, Bignell GR, Cox C, Stephens P, Edkins S et al.

    Nature 2002;417;6892;949-54

  • The chimeric protein tyrosine kinase ETV6-NTRK3 requires both Ras-Erk1/2 and PI3-kinase-Akt signaling for fibroblast transformation.

    Tognon C, Garnett M, Kenward E, Kay R, Morrison K and Sorensen PH

    Cancer research 2001;61;24;8909-16

  • ETV6-NTRK3 gene fusions and trisomy 11 establish a histogenetic link between mesoblastic nephroma and congenital fibrosarcoma.

    Knezevich SR, Garnett MJ, Pysher TJ, Beckwith JB, Grundy PE and Sorensen PH

    Cancer research 1998;58;22;5046-8