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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/17505

Title: Modulation of TGF‐β Receptor 1 signalling in Live Cells
Authors: Driscoll, Brandon
Advisor: Audet, Julie
Department: Biomedical Engineering
Keywords: TGF-β Inhibition
Peptide
ATP competitive inhibitor
neutralzing antibody
Issue Date: 7-Aug-2009
Abstract: TGF-β negatively affects the maintenance and expansion of hematopoietic stem cells ex vivo and its inhibition has been widely studied as a treatment for numerous hematopoietic disorders and cancers. Current inhibitory strategies (small molecule ATP competitors and neutralizing antibodies) are compared to a novel cell-permeable peptide-based inhibitor of TGF-β RI. Multiple levels of assay from biochemical to functional are utilized with the aim of applying the most successful inhibitor to hematopoietic stem cell culture. The neutralizing antibody proved ineffective in the short-term biochemical assay but was extremely effective at neutralizing TGF-β signalling in proliferation and hematopoietic colony-forming cell assays with no evidence of toxicity. The small molecule inhibitors (SD-208 and Pyrazole TGF-β RI inhibitor) were equally effective at micromolar levels in all forms of assay, with SD-208 being slightly more potent. The novel peptide inhibitor proved ineffective in all assays, which is likely a result of its rapid degradation in live cells.
URI: http://hdl.handle.net/1807/17505
Appears in Collections:Master
Institute of Biomaterials and Biomedical Engineering - Master theses

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