Signal Transduction in Normal Development and Disease
My research is directed towards understanding the regulation of protein interactions and signal-transduction pathways that control normal cellular function and human disease. Projects in the lab are currently focused within three main themes:
Regulation of signal transduction by adaptor proteins
My colleagues and I have focused the identification and functional characterization of intracellular adapter proteins that function to integrate, localize, and down regulate signal-transduction cascades. My laboratory has cloned and characterized a number of new adapters such as Gads and SLAP/SLAP2, which function in both growth factor and antigen-receptor signaling, as well as the adaptors NUMB, EHD and Lulu/Ymo1, which regulate the activity of trans-membrane receptors that determine cell fate and polarity during development. Currently,we are working on the functional characterization of these molecules, and their associated protein networks.
Ubiquitin dependent regulation of signal transduction and cell polarity
Our lab is studying the role of ubiquitin dependent regulation of signaling pathways. We have identified a family of novel E3 ubiquitin ligases, including LNX, and our current focus is to discover the role of LNX activity in cell fate determination and the establishment of cell polarity during embryonic development. Our lab has also recently discovered a novel ubiquitin ligase, that functions in receptor tyrosine kinase trafficking. We are currently developing high-throughput assays for LNX and RNF126 substrates and binding partners.
Development of high-throughput functional protein assays
As a co-director of Signaling and Degradation Network (SIDNET), at the Hospital for Sick Children , my lab is also involved in the development of high throughput assays of signal transduction and protein degradation pathways using robotics, protein arrays and high throughput detection and imaging systems. The SIDNET platform capabilities will continue to be expanded to include disease specific sets of cDNAs in multi-purpose expression formats, and shRNA libraries.
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