Western Australian Institute for Medical Research (WAIMR)


http://www.waimr.uwa.edu.au

Dr Robin Scaife

Robin Scaife

Following my PhD research in the laboratory of renowned cytoskeleton expert Les Wilson (UCSB), I was an NIH-sponsored postdoctoral scientist at the Fred Hutchinson Cancer Research Center in Seattle, USA. During this time I co-discovered the GTPase dynamin. Subsequently, as a researcher at the newly established Instititut de Biologie Structurale (Grenoble, France) I was among the first to determine the specificity of proline-motif interactions with Src homology 3 domains. This signal transduction research led to an investigation, at UWA, of cytoskeletal regulation. Currently, at WAIMR, I am investigating new aspects of cytoskeletal functions, as well as novel modes of gene regulation by nuclear bodies.

Qualifications

1980BSc (Hons) - Chemistry, University of Sussex, Brighton, United Kingdom
1986PhD - Biochemistry, University of California, Santa Barbara, United States
Thesis Title: "Identification and characterization of microtubule-associated proteins and enzymes"

Research Interests

  • Cytoskeletal regulation of proliferation and morphological differentiation.
  • Gene regulation by nuclear bodies.

Current Research

My current research interests lie primarily with cytoskeletal regulation of proliferation and morphological differentiation. Proliferation and morphological differentiation of cells are central to numerous human pathologies, as deregulated cell proliferation is the principle hall mark of cancer, while morphological differentiation is important in organ development and regeneration following injury. The cytoskeleton (a network of intracellular fibers) is involved in both proliferation and morphological differentiation. We have identified new modes of cytoskeletal regulation by signal transduction and microtubule-associated proteins that may be involved in neuritogenesis and human developmental disorders. Further exploration of these regulatory mechanisms could have significant direct human health implications.

Microtubules are also critically required for chromosome segregation during cell division (mitosis). Targeting of microtubules (e.g. by pharmacological agents such as Taxol®) is therefore one of the principal clinically applied anti-cancer strategies. We have identified a new synthetic pharmacophore that targets the microtubule cytoskeleton, as well as key components of the cell cycle machinery. By causing microtubule disassembly, this pharmacological agent causes inhibition of mitosis/cell division. Since perturbation of mitosis is central to most anti-cancer strategies, further development of this research programme may yield tangible progress in the development of new anti-cancer treatments.

Finally, we are also actively engaged in the investigation of gene regulation by nuclear bodies, and we are developing new screening technologies for signal transduction and high-content screening applications.

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

  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. 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]
  7. 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]
  8. 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]
  9. Scaife RM*. 2005. Selective and irreversible cell cycle inhibition by diphenyleneiodonium. Molecular Cancer Therapeutics 4(6):876-84. [NCBI PubMed Entry]
  10. 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