tyrosine kinase • adaptor proteins • acute kidney injury • cell signaling
My research focuses on acute kidney injury (AKI), a very common and deadly problem in hospitalized patients. My research seeks to better define the molecular basis of kidney cell injury and repair, particularly the role of special enzymes called tyrosine kinases and the signals they trigger inside injured cells. This work focuses on tyrosine kinases of the Src and Eph families and the role of an intracellular scaffolding protein called Dok-4, which regulates many of the responses triggered by tyrosine kinases. We are using biochemical and whole animal approaches to determine how tyrosine kinase pathways can be targeted to reduce AKI or accelerate its recovery in vivo, as well as how Dok-4 may function as a natural brake for these kinases and processes.
Hooker E, Baldwin C, Lemay S. New insights into Dok-4 PTB domain structure and function. Biochem Biophys Res Commun. 2012;427(1):67-72. PMID: 22982678.
Du X, Baldwin C, Hooker E, Glorion P, Lemay S. Basal and Src kinase-mediated activation of the EphA2 promoter requires a cAMP-responsive element but is CREB-independent. J Cell Biochem. 2011;112(5):1268-76. PMID: 21344481.
Bedirian A, Baldwin C, Abe J, Takano T, and Lemay S. PH and PTB domain-dependent membrane association and tyrosine phosphorylation of Dok-4, a novel inhibitory adapter protein expressed in epithelial cells. Journal of Biological Chemistry 2004; 279:19335-49. PMID: 14963042.
Lemay S, Davidson D, Latour S, and Veillette A. Dok-3, a novel adapter molecule involved in the negative regulation of immunoreceptor signaling. Molecular and Cellular Biology 2000; 20: 2743-2754. PMID: 10733577.
Lemay S, Rabb H, Postler G, and Singh AK. Prominent and sustained up-regulation of gp130-signaling cytokines and of the chemokine MIP-2 in murine ischemia-reperfusion injury. Transplantation 2000; 69: 959-963. PMID: 10755557.