Scientists Profile
Dr Robin Scaife
Following Dr Robin Scaifes PhD research in the laboratory of cytoskeleton expert Les Wilson (UCSB), Robin was an NIH-sponsored postdoctoral scientist with renowned cell cycle expert Bob Margolis at the Fred Hutchinson Cancer Research Center (FHCRC) in Seattle, USA. During this time Robin co-discovered the GTPase dynamin. Subsequently, as a researcher at the newly established Instititut de Biologie Structurale (Grenoble, France) Robin was among the first to determine the specificity of proline-motif interactions with Src homology 3 domains. This signal transduction research led to investigations, at UWA, of cytoskeletal and cell cycle regulation in addition to a collaboration with Professor Peter Klinken (WAIMR) regarding novel modes of gene regulation by nuclear bodies. Robin has recently spearheaded several drug discovery initiatives as the lead scientist at the BPH Laboratory based at the Western Australian Institute for Medical Research, Nedlands.
Qualifications
1980 BSc (Hons) - Chemistry, University of Sussex, Brighton, United Kingdom
1986 PhD - Biochemistry, University of California, Santa Barbara, United States
Thesis Title: "Identification and characterization of microtubule-associated proteins and enzymes"
Research Interests
Cytoskeletal dynamics and mitosis.
Cancer drug discovery and development.
Current Research
Dr Scaife's current research is focused on the discovery of new anti-cancer drugs. In 2007 he spearheaded the development of high-content imaging and analyses for drug discovery in the Molecular Discovery Systems (MDSystems) laboratory (SCGH). He has used this advanced technology to screen for new drugs among natural resources and synthetic chemical libraries. In addition to the identification of a new bioactive marine-derived extract, he has recently discovered a new class of anti-cancer drug. This new anti-cancer drug (compound 833) potently inhibits cell proliferation, resulting in pronounced killing of all human cancer cell lines tested to date. The cancer killing activity of this new drug is due to its effect on cell division (mitosis). In addition to development of this new drug through medicinal chemistry and preclinical testing, he is actively engaged in detailed cellular and biochemical analyses to establish its precise mode of action.
Further, Robin is developing high-content screening assays for use in fundamentally novel cancer drug discovery ventures.
Major Grants Awarded
Medical Research Foundation, Royal Perth Hospital, Research Grant (2005-2006) "Microtubule disassembly and inhibition of mitosis by a novel synthetic pharmacophore" - 12,000 AUD
Medical Research Foundation, Royal Perth Hospital, Research Grant (2004-2005) "Pharmacological down-regulation of cyclin B" - 15,000 AUD
Department of Health, Government of Western Australia, Medical and Health Research Infrastructure Fund (MHRIF) (2005) - 20,256 AUD
National Health and Medical Research Council (Australia): Project Grant (2000-2003) "Regulation of signal transduction by Cbl: investigation of effects on the cytoskeleton, cell adhesion and cell motility" (three year research grant as Chief Investigator (CIA) - 339,213 AUD
National Health and Medical Research Council (Australia): Project Grant, 1998-2000 "Modulation of receptor tyrosine kinase signaling by Cbl" (three year research grant as Chief Investigator (CIB) - 345,619 AUD
Medical Research Fund of Western Australia: Biomedical Research Grant (1997-1998) "Control of cell proliferation by Cbl proteins" - 97,000 AUD
Appel d'offres CNRS-ARC (France): subvention (1996-1997) "Interactions protéine-protéine dans l'assemblage de la dynamine et l'endocytose"
Top 10 Publications
Scaife RM, Margolis RL. 1990. Biochemical and immunochemical analysis of rat brain dynamin interaction with microtubules and organelles in vivo and in vitro. Journal of Cell Biology 111(6 Pt 2):3023-33. [NCBI PubMed Entry]
Scaife RM, Wilson L, Purich DL. 1992. Microtubule protein ADP-ribosylation in vitro leads to assembly inhibition and rapid depolymerization. Biochemistry 31(1):310-6. [NCBI PubMed Entry]
Scaife RM, Gout I, Waterfield MD, Margolis RL. 1994. Growth factor-induced binding of dynamin to signal transduction proteins involves sorting to distinct and separate proline-rich dynamin sequences. EMBO Journal 13(11):2574-82. [NCBI PubMed Entry]
Scaife RM*, Langdon WY. 2000. c-Cbl localizes to actin lamellae and regulates lamellipodia formation and cell morphology. Journal of Cell Science 113 Pt 2:215-26. [NCBI PubMed Entry]
Scaife RM*, Courtneidge SA, Langdon WY. 2003. The multi-adaptor proto-oncoprotein Cbl is a key regulator of Rac and actin assembly. Journal of Cell Science 116(Pt 3):463-73. [NCBI PubMed Entry] Thien CB, Scaife RM, Papadimitriou J, Murphy MA, Bowtell DL, Langdon WY. 2003. A mouse with a loss-of-function mutation in the c-Cbl TKB domain shows perturbed thymocyte signaling without enhancing the activity of the ZAP-70 tyrosine kinase. Journal of Experimental Medicine 197(4):503-13. [NCBI PubMed Entry]
Scaife RM*, Job D, Langdon WY. 2003. Rapid microtubule-dependent induction of neurite-like extensions in NIH 3T3 fibroblasts by inhibition of ROCK and Cbl. Molecular Biology of the Cell 14(11):4605-17. [NCBI PubMed Entry]
Scaife RM*. 2004. G2 cell cycle arrest, down-regulation of cyclin B, and induction of mitotic catastrophe by the flavoprotein inhibitor diphenyleneiodonium. Molecular Cancer Therapeutics 3(10):1229-37. [NCBI PubMed Entry]
Scaife RM*. 2005. Selective and irreversible cell cycle inhibition by diphenyleneiodonium. Molecular Cancer Therapeutics 4(6):876-84. [NCBI PubMed Entry]
Scaife RM*. 2006. Microtubule disassembly and inhibition of mitosis by a novel synthetic pharmacophore. Journal of Cellular Biochemistry 98(1):102-14. [NCBI PubMed Entry]
* Listed as Corresponding Author
