Research Description:
Dr. Greg Miller earned is Ph.D. at the University of Western Ontario in London, ON in 2001. He then spent 5 years as a Visiting Fellow at the National Institute of Diabetes, Digestive and Kidney Diseases at the NIH in Bethesda, MD. Dr. Miller joined the Department of Pharmacology and Therapeutics as an Assistant Professor at McGill University in August, 2006.
The Miller lab couples structural biology with other approaches to study kinases and phosphatases that produce soluble inositol phosphate (IP) and membrane-bound phosphatidylinositol (PI) signals in cells. Inositol-based signals are ubiquitous in human cells and are known to play important roles in healthy cells and in disease conditions. Our goal is to understand how these kinases and phosphatases produce these highly specific inositol signals and how they elicit their effects in cells. To do this, we study the structures of the IP and PI kinases and phosphatases, their catalytic mechanisms, and how their actions are regulated in the cell. We use x-ray crystallography to determine the high-resolution structures of these enzymes and protein engineering to correlate the structure of each enzyme with its catalytic function. Using these approaches we generate a clear understanding of the functions of these kinases and phosphatases and we also obtain high-resolution structures to facilitate inhibitor and drug design efforts to target inositol-based signaling networks to treat cancer and cystic fibrosis.
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Selected Publications:
Miller, G.J., Wilson, M.P., Majerus, P.W., Hurley, J.H. (2005) Specificity determinants in inositol polyphosphate synthesis: crystal structure of inositol 1,3,4-trisphosphate 5/6-kinase., Mol. Cell, 18, 201-212.
Miller, G.J., Hurley, J.H. (2004) Crystal Structure of the Catalytic Core of Inositol 1,4,5-Trisphosphate 3-Kinase., Mol. Cell,15, 703-711.
Miller, G.J., Mattera, R., Bonifacino, J.S., Hurley, J.H. Recognition of accessory protein motifs by the gamma-adaptin ear domain of GGA3., (2003) Nat. Struct. Biol. 10, 599-606.
Misra, S., Miller, G.J., Hurley, J.H., Recognizing phosphatidylinositol 3-phosphate. (2001) Cell, 107, 559-562.
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