The London Research Institute research groups are based at Lincoln’s Inn Fields and Clare Hall. Our major research themes are: the biology of tumours and tissues, cellular regulatory mechanisms and genomic integrity and cell cycle.
Julian Downward : Signal Transduction
Goals
Previous and current research
Our interests include the mechanisms by which cells respond to external signals that regulate their proliferation and survival, in particular the signalling pathways along which information is transferred leading from cell surface receptors to events in the cell nucleus, and how these are altered during the process of malignant transformation. We have characterised the molecular details of how Ras oncoproteins, which are mutationally activated in 30% of human tumours, are regulated and how they transmit their signal to the cell through direct binding to multiple effector proteins including Raf and phosphatidylinositol 3-kinase.
Future projects
We are using whole genome scale RNA interference libraries to identify new components of critical growth regulatory pathways. In addition we are screening for genes that are required for the survival of Ras transformed, but not normal, cells and also for genes that when disrupted may restore the sensitivity of drug resistant tumour cells to established chemotherapeutic agents.
Selected Papers
Michl P, Ramjaun AR, Pardo OE, Warne PH, Wagner M, Poulsom R, D'Arrigo C, Ryder K, Menke A, Gress T, Downward J. CUTL1 is a target of TGFb signaling that enhances cancer cell motility and invasiveness. Cancer Cell. 2005;7:521-532
(Abstract)
Nicke B, Bastien J, Khanna SJ, Warne PH, Cowling V, Cook SJ, Peters G, Delpuech O, Schulze A, Berns K, Mullenders J, Beijersbergen RL, Bernards R, Ganesan TS, Downward J, Hancock DC. Involvement of MINK, a Ste20 family kinase, in Ras oncogene-induced growth arrest in human ovarian surface epithelial cells. Molecular Cell. 2005;20:673-685
(Abstract)
Basu S, Totty NF, Irwin MS, Sudol M, Downward J. Akt Phosphorylates the Yes-Associated Protein, YAP, to induce interaction with 14-3-3 and attenuation of p73-mediated apoptosis. Molecular Cell. 2003;11:11-23
(Abstract)
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Julian Downward
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