Transgenic Technology
Group Leader:
Douglas Strathdee
The Transgenic Technology Laboratory makes use of molecular genetic approaches to understand gene function and how that is altered in the emergence and progression of cancers. We can closely mimic changes in genes seen in human cancers by using tools like gene targeting or genome editing. By combining specific gene changes, we create detailed models of human cancers that help us understand how these genetic changes drive disease progression. Embryonic stem (ES) cells are useful for making new cancer models because they have two important features. First, ES cells have a high ability for homologous recombination (HR), letting us precisely change genes and add mutations found in human cancers. Second, ES cells can develop into many different cell types from various tissues. So, after making the right genetic changes in ES cells, we can turn them into the tissue cells we want to study. Over the past year, we worked with other groups at the Institute to create many types of altered genes. These included conditional knockouts, point mutations, and inducible transgenes. This method lets us introduce mutations directly into the natural gene setting, making sure our changes closely match those seen in human cancers. We also used these studies to find genetic factors that affect how the disease progresses. Discovering these factors not only helps us understand the disease better but also points to possible targets for new treatments.
Lab Members
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Recent Publications
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Recent Publications
2025
Hashemi, A., Liu, M.R., Chan, J.Z., Berdeklis, A.N., Cocco, A.D., Tomczewski, M.V., Strathdee, D., Stark, K.D., Duncan, R.E., 2025. Plaat1 deficiency reduces cardiac cardiolipin content and impairs exercise tolerance. J Lipid Res 100822.
Kanellos, G., Giacomelli, C., Raven, A., Vlahov, N., Jin, H., Herviou, P., Malla, S.B., Nasreddin, N., Centeno, P.P., Alexandrou, C., Gilroy, K., Baird, R.L., Pennel, K., Munro, J., Waldron, J.A., Hall, H., Officer-Jones, L., Bryson, S., Strathdee, D., Lilla, S., Zanivan, S., Morrison, V., Nixon, C., Ridgway, R.A., Miller, C., Knight, J.R.P., Campbell, A.D., Dunne, P.D., Le Quesne, J., Edwards, J., Park, P.J., Bushell, M., Sansom, O.J., 2025. Nucleophosmin supports WNT-driven hyperproliferation and tumor initiation. Nat Genet 58, 100–115.
Raven, A., Gilroy, K., Jin, H., Waldron, J.A., Leslie, H., Munro, J., Hall, H., Ridgway, R.A., Ford, C.A., Gulhan, D.C., Vlahov, N., Mills, M.L., Hartley, A., Anderson, E., Bryson, S., Sphyris, N., Müller, M., May, S., Cadden, B., Nixon, C., Waddell, S.H., Guest, R., Boulter, L., Barker, N., Clevers, H., Zhu, H., Ivaska, J., Strathdee, D., Miller, C.J., Jamieson, N.B., Bushell, M., Park, P.J., Bird, T.G., Sansom, O.J., 2025. Hepatic zonation determines tumorigenic potential of mutant β-catenin. Nature 649, 739–748.
Zakrzewski, P., Rice, C.M., Fleming, K., Cela, D., Groves, S.J., Ponce-Garcia, F.M., Gibbs, W., Roberts, K., Pike, T., Strathdee, D., Anderson, E., Nobbs, A.H., Toye, A.M., Steward, C., Amulic, B., 2025. Tafazzin regulates neutrophil maturation and inflammatory response. EMBO Rep.
2024
Cheung, E.C., Strathdee, D., Stevenson, D., Coomes, J., Blyth, K., Vousden, K.H., 2024. Regulation of ROS signaling by TIGAR induces cancer-modulating responses in the tumor microenvironment. Proc Natl Acad Sci U S A 121(50), e2416076121.
Najumudeen, A.K., Fey, S.K., Millett, L.M., Ford, C.A., Gilroy, K., Gunduz, N., Ridgway, R.A., Anderson, E., Strathdee, D., Clark, W., Nixon, C., Morton, J.P., Campbell, A.D., Sansom, O.J., 2024. KRAS allelic imbalance drives tumour initiation yet suppresses metastasis in colorectal cancer in vivo. Nat Commun 15(1), 100.
Whyte, D., Voorde, J.V., Sumpton, D., Dhayade, S., Dornier, E., Moore, M., Novo, D., Peters, J., Wiesheu, R., Mackey, J.B.G., McFarlane, A.J., Fercoq, F., Fisher, S., Caballero, C.D., Gilroy, K., Redmond, K.L., Mitchell, L.E., Anderson, E., Thomson, G., Dzierozynski, L.N., Saab, J.J.A., Lewis, C.A., Muir, A., Halbrook, C.J., Strathdee, D., Jackstadt, R., Nixon, C., Dunne, P., Steele, C.W., Carlin, L.M., Macpherson, I.R., Roberts, E.W., Coffelt, S.B., Blyth, K., Sansom, O.J., Norman, J.C., Clarke, C.J., 2024. Uridine Phosphorylase-1 supports metastasis of mammary cancer by altering immune and extracellular matrix landscapes of the lung. bioRxiv.
2023
Hennequart, M., Pilley, S.E., Labuschagne, C.F., Coomes, J., Mervant, L., Driscoll, P.C., Legrave, N.M., Lee, Y., Kreuzaler, P., Macintyre, B., Panina, Y., Blagih, J., Stevenson, D., Strathdee, D., Schneider-Luftman, D., Grönroos, E., Cheung, E.C., Yuneva, M., Swanton, C., Vousden, K.H., 2023. ALDH1L2 regulation of formate, formyl-methionine, and ROS controls cancer cell migration and metastasis. Cell Rep 42, 112562.
Moore, M., Pardo, L., Mitchell, L., Schmidt, T., May, S., Mueller, M., Strathdee, D., Bryson, S., Hodge, K., Lilla, S., Zanivan, S., Waldron, J., McGarry, L., Peter-Durairaj, R., Kanellos, G., Nixon, C., Ballantyne, F., LeQuesne, J., Sansom, O.J., Bird, T., Bushell, M., Norman, J.C., 2023. The eIF4A2 negative regulator of mRNA translation promotes extracellular matrix deposition to accelerate hepatocellular carcinoma initiation. bioRxiv.
Perera, G., Power, L., Larson, A., Codden, C.J., Awata, J., Batorsky, R., Strathdee, D., Chin, M.T., 2023. Single Cell Transcriptomic Analysis in a Mouse Model of Barth Syndrome Reveals Cell-Specific Alterations in Gene Expression and Intercellular Communication. Int J Mol Sci 24, 11594.
Tomczewski, M.V., Chan, J.Z., Campbell, Z.E., Strathdee, D., Duncan, R.E., 2023. Phenotypic Characterization of Male Tafazzin-Knockout Mice at 3, 6, and 12 Months of Age. Biomedicines 11, 638.
Wang, S., Yazawa, E., Keating, E., Mazumdar, N., Hauschild, A., Ma, Q., Wu, H., Xu, Y., Shi, X., Strathdee, D., Gerszten, R.E., Schlame, M., Pu, W.T., 2023. Genetic modifiers modulate phenotypic expression of tafazzin deficiency in a mouse model of Barth syndrome. Hum Mol Genet 32, 2055–2067.
2022
Baudot, A.D., Wang, V.M., Leach, J.D., O'Prey, J., Long, J.S., Paulus-Hock, V., Lilla, S., Thomson, D.M., Greenhorn, J., Ghaffar, F., Nixon, C., Helfrich, M.H., Strathdee, D., Pratt, J., Marchesi, F., Zanivan, S., Ryan, K.M., 2022. Glycan degradation promotes macroautophagy. Proc Natl Acad Sci U S A 119(26), e2111506119.
Flanagan, D.J., Amirkhah, R., Vincent, D.F., Gundaz, N., Gentaz, P., Cammareri, P., McCooey, A.J., McCorry, A.M.B., Fisher, N.C., Davis, H.L., Ridgway, R.A., Lohuis, J., Leach, J.D.G., Jackstadt, R., Gilroy, K., Mariella, E., Nixon, C., Clark, W., Hedley, A., Markert, E.K., Strathdee, D., Bartholin, L., Redmond, K.L., Kerr, E.M., Longley, D.B., Ginty, F., Cho, S., Coleman, H.G., Loughrey, M.B., Bardelli, A., Maughan, T.S., Campbell, A.D., Lawler, M., Leedham, S.J., Barry, S.T., Inman, G.J., van Rheenen, J., Dunne, P.D., Sansom, O.J., 2022. Epithelial TGFβ engages growth-factor signalling to circumvent apoptosis and drive intestinal tumourigenesis with aggressive features. Nat Commun 13, 7551.
Humpton, T.J., Hock, A.K., Kiourtis, C., De Donatis, M., Fercoq, F., Nixon, C., Bryson, S., Strathdee, D., Carlin, L.M., Bird, T.G., Blyth, K., Vousden, K.H., 2022. A noninvasive iRFP713 p53 reporter reveals dynamic p53 activity in response to irradiation and liver regeneration in vivo. Sci Signal 15, eabd9099.
2021
Gudiño, V., Pohl, S., Billard, C.V., Cammareri, P., Bolado, A., Aitken, S., Stevenson, D., Hall, A.E., Agostino, M., Cassidy, J., Nixon, C., von Kriegsheim, A., Freile, P., Popplewell, L., Dickson, G., Murphy, L., Wheeler, A., Dunlop, M., Din, F., Strathdee, D., Sansom, O.J., Myant, K.B., 2021. RAC1B modulates intestinal tumourigenesis via modulation of WNT and EGFR signalling pathways. Nat Commun 12, 2335.
Humpton, T.J., Nomura, K., Weber, J., Magnussen, H.M., Hock, A.K., Nixon, C., Dhayade, S., Stevenson, D., Huang, D.T., Strathdee, D., Blyth, K., Vousden, K.H., 2021. Differential requirements for MDM2 E3 activity during embryogenesis and in adult mice. Genes & development 35(1-2), 117–132.
Julian, L., Naylor, G., Wickman, G.R., Rath, N., Castino, G., Stevenson, D., Bryson, S., Munro, J., McGarry, L., Mullin, M., Rice, A., Del Río Hernández, A., Olson, M.F., 2021. Defective apoptotic cell contractility provokes sterile inflammation, leading to liver damage and tumour suppression. eLife 10, e61983.
Leach, J.D.G., Vlahov, N., Tsantoulis, P., Ridgway, R.A., Flanagan, D.J., Gilroy, K., Sphyris, N., Vázquez, E.G., Vincent, D.F., Faller, W.J., Hodder, M.C., Raven, A., Fey, S., Najumudeen, A.K., Strathdee, D., Nixon, C., Hughes, M., Clark, W., Shaw, R., van Hooff, S.R., Huels, D.J., Medema, J.P., Barry, S.T., Frame, M.C., Unciti-Broceta, A., Leedham, S.J., Inman, G.J., Jackstadt, R., Thompson, B.J., Campbell, A.D., Tejpar, S., Sansom, O.J., 2021. Oncogenic BRAF, unrestrained by TGFβ-receptor signalling, drives right-sided colonic tumorigenesis. Nat Commun 12, 3464.
Najumudeen, A.K., Ceteci, F., Fey, S.K., Hamm, G., Steven, R.T., Hall, H., Nikula, C.J., Dexter, A., Murta, T., Race, A.M., Sumpton, D., Vlahov, N., Gay, D.M., Knight, J.R.P., Jackstadt, R., Leach, J.D.G., Ridgway, R.A., Johnson, E.R., Nixon, C., Hedley, A., et al., 2021. The amino acid transporter SLC7A5 is required for efficient growth of KRAS-mutant colorectal cancer. Nat Genet 53, 16–26.
Pickering, K.A., Gilroy, K., Cassidy, J.W., Fey, S.K., Najumudeen, A.K., Zeiger, L.B., Vincent, D.F., Gay, D.M., Johansson, J., Fordham, R.P., Miller, B., Clark, W., Hedley, A., Unal, E.B., Kiel, C., McGhee, E., Machesky, L.M., Nixon, C., Johnsson, A.E., Bain, M., et al., 2021. A RAC-GEF network critical for early intestinal tumourigenesis. Nat Commun 12, 56.
Swaminathan, K., Campbell, A., Papalazarou, V., Jaber-Hijazi, F., Nixon, C., McGhee, E., Strathdee, D., Sansom, O.J., Machesky, L.M., 2021. The RAC1 Target NCKAP1 Plays a Crucial Role in the Progression of Braf;Pten-Driven Melanoma in Mice. J Invest Dermatol 141(3), 628–637.e615.
2020
Corrado, M., Edwards-Hicks, J., Villa, M., Flachsmann, L.J., Sanin, D.E., Jacobs, M., Baixauli, F., Stanczak, M., Anderson, E., Azuma, M., Quintana, A., Curtis, J.D., Clapes, T., Grzes, K.M., Kabat, A.M., Kyle, R., Patterson, A.E., Geltink, R.K., Amulic, B., Steward, C.G., Strathdee, D., Trompouki, E., O'Sullivan, D., Pearce, E.J., Pearce, E.L., 2020. Dynamic Cardiolipin Synthesis Is Required for CD8(+) T Cell Immunity. Cell Metab 32(6), 981–995.e987.
Loveridge, C.J., Slater, S., Campbell, K.J., Nam, N.A., Knight, J., Ahmad, I., Hedley, A., Lilla, S., Repiscak, P., Patel, R., Salji, M., Fleming, J., Mitchell, L., Nixon, C., Strathdee, D., Neilson, M., Ntala, C., Bryson, S., Zanivan, S., Edwards, J., Robson, C.N., Goodyear, C.S., Blyth, K., Leung, H.Y., 2020. BRF1 accelerates prostate tumourigenesis and perturbs immune infiltration. Oncogene 39, 1797–1806.
Nobis, M., Herrmann, D., Warren, S.C., Strathdee, D., Cox, T.R., Anderson, K.I., Timpson, P., 2020. Shedding new light on RhoA signalling as a drug target in vivo using a novel RhoA-FRET biosensor mouse. Small GTPases 11(4), 240–247.
Swaminathan, K., Campbell, A., Papalazarou, V., Jaber-Hijazi, F., Nixon, C., McGhee, E., Strathdee, D., Sansom, O.J., Machesky, L.M., 2020. The RAC1 target NCKAP1 plays a crucial role in progression of BRAF/PTEN -driven melanoma in mice. J Invest Dermatol.
Wang, S., Li, Y., Xu, Y., Ma, Q., Lin, Z., Schlame, M., Bezzerides, V.J., Strathdee, D., Pu, W.T., 2020. AAV Gene Therapy Prevents and Reverses Heart Failure in A Murine Knockout Model of Barth Syndrome. Circulation research 126, 1024–1039.
2018
Christodoulou, N., Weberling, A., Strathdee, D., Anderson, K.I., Timpson, P., Zernicka-Goetz, M., 2019. Morphogenesis of extra-embryonic tissues directs the remodelling of the mouse embryo at implantation. Nature communications 10, 3557.
Liko, D., Mitchell, L., Campbell, K.J., Ridgway, R.A., Jones, C., Dudek, K., King, A., Bryson, S., Stevenson, D., Blyth, K., Strathdee, D., Morton, J.P., Bird, T.G., Knight, J.R.P., Willis, A.E., Sansom, O.J., 2019. Brf1 loss and not overexpression disrupts tissues homeostasis in the intestine, liver and pancreas. Cell Death Differ 26, 2535–2550.
Ren, M., Xu, Y., Erdjument-Bromage, H., Donelian, A., Phoon, C.K.L., Terada, N., Strathdee, D., Neubert, T.A., Schlame, M., 2019. Extramitochondrial cardiolipin suggests a novel function of mitochondria in spermatogenesis. J Cell Biol 218(5), 1491–1502.
Schmidt, S., Gay, D., Uthe, F.W., Denk, S., Paauwe, M., Matthes, N., Diefenbacher, M.E., Bryson, S., Warrander, F.C., Erhard, F., Ade, C.P., Baluapuri, A., Walz, S., Jackstadt, R., Ford, C., Vlachogiannis, G., Valeri, N., Otto, C., Schulein-Volk, C., Maurus, K., Schmitz, W., Knight, J.R.P., Wolf, E., Strathdee, D., Schulze, A., Germer, C.T., Rosenwald, A., Sansom, O.J., Eilers, M., Wiegering, A., 2019. A MYC-GCN2-eIF2alpha negative feedback loop limits protein synthesis to prevent MYC-dependent apoptosis in colorectal cancer. Nature cell biology 21, 1413–1424.
2018
Konjar, S., Frising, U.C., Ferreira, C., Hinterleitner, R., Mayassi, T., Zhang, Q., Blankenhaus, B., Haberman, N., Loo, Y., Guedes, J., Baptista, M., Innocentin, S., Stange, J., Strathdee, D., Jabri, B., et al., 2018. Mitochondria maintain controlled activation state of epithelial-resident T lymphocytes. Sci Immunol 3(24), eaan2543.
Lou, W., Reynolds, C.A., Li, Y., Liu, J., Huttemann, M., Schlame, M., Stevenson, D., Strathdee, D., Greenberg, M.L., 2018. Loss of tafazzin results in decreased myoblast differentiation in C2C12 cells: A myoblast model of Barth syndrome and cardiolipin deficiency. Biochim Biophys Acta 1863(8), 857–65.
Nobis, M., Herrmann, D., Warren, S.C., Strathdee, D., Cox, T.R., Anderson, K.I., Timpson, P., 2018. Shedding new light on RhoA signalling as a drug target in vivo using a novel RhoA-FRET biosensor mouse. Small GTPases.
Warren, S.C., Nobis, M., Magenau, A., Mohammed, Y.H., Herrmann, D., Moran, I., Vennin, C., Conway, J.R., Melenec, P., Cox, T.R., Wang, Y., Morton, J.P., Welch, H.C., Strathdee, D., Anderson, K.I., et al., 2018. Removing physiological motion from intravital and clinical functional imaging data. Elife 7, e35800.
Woroniuk, A., Porter, A., White, G., Newman, D.T., Diamantopoulou, Z., Waring, T., Rooney, C., Strathdee, D., Marston, D.J., Hahn, K.M., Sansom, O.J., Zech, T., Malliri, A., 2018. STEF/TIAM2-mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap. Nat Commun 9(1), 2124.
2017
Hock, A.K., Cheung, E.C., Humpton, T.J., Monteverde, T., Paulus-Hock, V., Lee, P., McGhee, E., Scopelliti, A., Murphy, D.J., Strathdee, D., Blyth, K., Vousden, K.H., 2017. Development of an inducible mouse model of iRFP713 to track recombinase activity and tumour development in vivo. Sci Rep 7, 1837.
Nobis, M., Herrmann, D., Warren, S.C., Kadir, S., Leung, W., Killen, M., Magenau, A., Stevenson, D., Lucas, M.C., Reischmann, N., Vennin, C., Conway, J.R.W., Boulghourjian, A., Zaratzian, A., Law, A.M., Gallego-Ortega, D., Ormandy, C.J., Walters, S.N., Grey, S.T., Bailey, J., et al., 2017. A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts. Cell Rep 21, 274–88.
van de Lagemaat, L.N., Stanford, L.E., Pettit, C.M., Strathdee, D.J., Strathdee, K.E., Elsegood, K.A., Fricker, D.G., Croning, M.D., Komiyama, N.H., Grant, S.G., 2017. Standardized experiments in mutant mice reveal behavioural similarity on 129S5 and C57BL/6J backgrounds. Genes Brain Behav 16, 409–18.
2016
Birch, J., Clarke, C.J., Campbell, A.D., Campbell, K., Mitchell, L., Liko, D., Kalna, G., Strathdee, D., Sansom, O.J., Neilson, M., Blyth, K., Norman, J.C., 2016. The initiator methionine tRNA drives cell migration and invasion leading to increased metastatic potential in melanoma. Biol Open 5, 1371–1379.
Walton, J., Blagih, J., Ennis, D., Leung, E., Dowson, S., Farquharson, M., Tookman, L.A., Orange, C., Athineos, D., Mason, S., Stevenson, D., Blyth, K., Strathdee, D., Balkwill, F.R., Vousden, K.H., Lockley, M., McNeish, I.A., 2016. CRISPR/Cas9-mediated Trp53 and Brca2 knockout to generate improved murine models of ovarian high grade serous carcinoma. Cancer Res 76(20), 6118–6129.
Group Leader
Douglas Strathdee*
Information about this team member’s research interests, experience, and background will be added soon. Please check back for updates.
D.Strathdee@crukscotlandinstitute.ac.uk