Bachelor of Science with Honors, Adelaide University
Doctor of Philosophy, Adelaide University
Post-Doctoral Training, Stanford University
Edna Seinsheimer Levin Endowed Professorship in Cancer Studies
R.R. Bensley Scholar, 1997
Cancer invasion and metastasis (which involves the spread of tumor cells from one site to another) are events that involve abnormal or increased signaling from multiple signaling receptors, including the Hepatocyte Growth Factor Receptor (Met). Met is a receptor tyrosine kinase that normally functions to regulate proper cell growth and motility during development and wound repair. In adult tissues, increased Met signaling occurs in multiples cancers correlating closely with high metastatic potential, angiogenesis and poor patient prognosis. A key process for terminating Met signaling involves the removal of receptors from the cell surface by endocytosis followed by receptor downregulation in lysosomes. A major focus of my lab is to define the molecular and cellular mechanisms linking receptor trafficking with receptor signaling. Our studies focus on the Met receptor tyrosine kinase, with a particular emphasis on the role of Met signaling in the progression of metastatic Pancreatic and Head and Neck cancers. We are currently studying the endocytic mechanisms that remove Met from the cell surface and are exploring how these processes may be corrupted in tumor cells. We are particularly interested in the sorting mechanisms that determine the specificity of receptor down regulation and whether novel therapeutics can be developed to treat cancers in which the inactivation of these processes facilitates metastasis. Many of our studies are conducted using mammalian cell culture systems in which we apply a variety of biochemical, molecular and genetic methodologies to understand specific mechanisms of receptor trafficking. We are refining newer cellular imaging techniques to examine receptor trafficking in living tissues and are investigating the functional effects of specific trafficking mechanisms on cancer metastasis using state-of-the-art physiological approaches.
Select PublicationsSheth PR, Hays JL, Elferink LA., Watovich SJ. (2008) Modeling the competing processes regulating hepatocye growth factor receptor (c-Met) activation. Biochemistry. 2008 Apr 1;47(13):4028-38.
Li N, Lorinczi M, Ireton K, Elferink LA. (2007) Specific Grb2-mediated interactions regulate clathrin-dependent endocytosis of the cMet tyrosine kinase. J Biol Chem 282(23):16764-75.
Elferink LA, Strick DJ. (2005) Functional properties of rab15 effector protein function in endocytic recycling.Â Methods Enzymol 403:732-43.
Strick DJ, Elferink LA. (2005) Rab15 effector protein: a novel protein for receptor recycling from pericentriolar recycling endosomes Mol Biol Cell 16(12):5699-5709.
Li N, Xiang GS, Dokainish H, Ireton K, Elferink LA. (2005) The Listeria protein InlB mimics hepatocyte growth factor-induced receptor trafficking. Traffic 6, 459-473.