The Henning Walczak Lab
Professor Henning Walczak, PhD
Scientific Director of the Cancer Research UK-UCL Centre
Head of the Department of Cancer Biology
Group Leader: Cell Death, Cancer and Inflammation Research Group
Research in the Walczak Laboratory is focused on cell death and ubiquitin in inflammation, cancer and immunity. The lab is particularly interested in unravelling the mechanisms on how different death receptor-ligand systems such as the TNF and TRAIL systems are regulated and how they impact cancer cell survival, cancer-related inflammation and immunity. The research aims are to develop novel cancer therapies by specifically inducing cancer cell death and by therapeutically directing the type of death induced in cancer cells to convert cancer-related inflammation from being immune-regulatory to enabling the immune system to recognise and kill cancer cells.
Lewis M., Vyse S., Shields A., Boeltz S., Gordon P., Spector T., Lehner P., Walczak H., Vyse T. Effect of UBE2L3 genotype on regulation of the linear ubiquitin chain assembly complex in systemic lupus erythematosus. Lancet 385 Suppl 1:S9, 2015.
Von Karstedt, S., Conti, A., Nobis, M., Montinaro, A., Hartwig, T., Lemke, J., Legler, K., Annewanter, F., Campbell, A.D., Taraborrelli, L., Grosse-Wilde, A., Coy, J.F., El-Bahrawy, M.A., Bergmann, F., Koschny, R., Werner, J., Ganten, T.M., Schweiger, T., Hoetzenecker, K., Kenessey, I., Hegedüs, B., Bergmann, M., Hauser, C., Egberts, J.H., Becker, T., Röcken, C., Kalthoff, H., Trauzold, A., Anderson, K.I., Sansom, O.J., Walczak, H. Cancer Cell-Autonomous TRAIL-R Signaling Promotes KRAS-Driven Cancer Progression, Invasion, and Metastasis. Cancer Cell, 27(4):561-73, 2015.
Peltzer, N., Rieser, E., Taraborrelli, L., Draber, P., Darding, M., Pernaute, B., Shimizu, Y., Daboh, A., Draberova, H., Montinaro, A., Martinez-Barbera, J.P., Silke, J., Rodriguez, T.A. and Walczak, H. HOIP deficiency caused embryonic lethality by aberrant TNFR1-mediated endothelial cell death. Cell Reports 9(1): 153-165, 2014.
Lemke, J., Von Karstedt, S., Abd El Hay, M., Conti, A., Arce, F., Montinaro, A., Papenfuss, K., El-Bahrawy, M. A. and Walczak, H. Selective CDK9 Inhibition Overcomes TRAIL Resistance by Concomitant Suppression of cFlip and Mcl-1. Cell Death and Differentiation 21: 491-502, 2014.
Gerlach, B., Cordier, S.M., Schmukle, A.C., Emmerich, C.H., Rieser, E., Haas, T.L., Webb, A.I., Rickard, J.A., Anderton, H., Wong, W.W.-L., Nachbur, U., Gangoda, L., Warnken, U., Purcell, A.W., Silke, J., Walczak, H. Linear ubiquitination prevents inflammation and regulates immune signalling. Nature 471:591-596, 2011.
Haas, T.L., Emmerich, C.H., Gerlach, B., Schmukle, A.C., Cordier., S.M., Rieser, E., Feltham, R., Vince, J., Warnken, U., Wenger, T., Koschny, R., Komander, D., Silke, J., Walczak, H.Recruitment of the linear ubiquitin chain assembly complex (LUBAC) stabilizes the TNF-R1 signaling complex and is required for TNF-mediated gene induction. Molecular Cell 36: 831-844, 2009.
Accelerating Immunotherapy - £5 million award to new research collaboration led by Professor Henning Walczak
Cancer Research UK has awarded one of the first 2015 Network Accelerator Awards to the Cancer Research UK-UCL Centre based at UCL Cancer Institute. The award brings together a network of immunologists, cancer biologists and cancer immunotherapists across Centres and Institutes in London, and will also help the next generation of scientists to develop careers in the field.
Body’s defences hijacked to make cancers more aggressive
UCL scientists have discovered that a vital self-destruct switch in cells is hijacked - making some pancreatic and non small cell lung cancers more aggressive, according to research published in Cancer Cell. The team, from the Cancer Research UK Centre at the UCL Cancer Institute, found that mutations in the KRAS gene interferes with protective self-destruct switches, known as TRAIL receptors, which usually help to kill potentially cancerous cells.
Scientists trigger self-destruct switch in lung cancer cells
Cancer Research UK scientists have found a drug combination that can trigger the self-destruct process in lung cancer cells - paving the way for new treatments, according to research presented at the National Cancer Research Institute (NCRI) Cancer Conference.
When healthy cells are no longer useful they initiate a chain of events culminating in self destruction. But cancer cells swerve away from this suicide path and become immortal. This means that cells grow out of control – causing tumours to form.
The Cancer Research UK team, based at the UCL Cancer Institute, has successfully fixed this fault in lung cancer cells – reprogramming the cells to self-destruct.