Mount Sinai Hospital
Joseph and Wolf Lebovic Health Complex
600 University Ave.
Toronto ON M5T 3L9
Tel.: 416-586-4800 ext. 3018
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Dr. Karen Colwill joined Dr. Tony
Pawson's laboratory in 2002 to help coordinate large-scale
projects and collaborations. Work in the Pawson laboratory is centred on
understanding how signals originating from outside the cell are
interpreted by components within the cell to generate the appropriate
cellular response. This cellular response is dictated in large part by
the interaction between proteins that are dynamically organized into
vast networks - aberrations within these networks can lead to
complex diseases such as cancer.
Specifically, Dr. Colwill is
investigating the role and functioning of kinases (enzymes that modify
proteins through the addition of a phosphate group), which are critical
regulatory nodes within these protein interaction networks. Dr.
Colwill is leading a large-scale effort to clone all the human protein
kinases and analyze their interaction networks using the latest mass
spectrometry technology. Combining this knowledge of physical
interaction networks with concurrent phenotypic screens for kinase
function will help identify which kinases are critical in relaying
specific extracellular signals and may suggest potential therapeutic
The ability to inhibit aberrant
protein-protein interactions has great therapeutic potential. Dr.
Colwill is coordinating a research program between Dr. Pawson and Dr.
Jeff Wrana at the Lunenfeld-Tanenbaum, Dr. Shawn Li at the University
of Western Ontario and Dr. Andrei Yudin at the University of Toronto to
test the efficacy of using macrocyclic peptides to block
protein-protein interactions. Macrocyclic peptides (those that
have been cyclized and are no longer linear) have an extended binding
surface compared with small molecules. As such, they are more
suited to block interactions between modular domains such as SH2, WW
and SH3 domains and the cognate binding motifs on their target
One of the challenges in science
is the lack of appropriate reagent tools. To help overcome this
challenge, Drs. Colwill and Pawson are working with Dr. Sachdev Sidhu
and other scientists to create in vitro synthesized antibodies
as probes to investigate protein-protein interaction
networks. Having recently generated synthetic antibodies to SH2
domain targets, the focus has now switched to creating antibodies
against cell surface receptors, which can function as both laboratory
reagents and as potential therapeutics.
To investigate protein interaction
networks in a high-throughput manner, it is imperative to have an
extensible and flexible system for documenting reagents. Dr.
Colwill has led the effort at the Lunenfeld-Tanenbaum to create an
open-source reagent information software system to track the properties
and locations of all reagents used within the
This repository, OpenFreezer,
tracks over 150,000 reagents at the Lunenfeld-Tanenbaum. The
latest version of the OpenFreezer software is available for free
download at http://openfreezer.org/.