Fred Keeley

Fred Keeley was born and raised in Winnipeg where he completed an undergraduate degree in Chemistry and a PhD in Pharmacology at the University of Manitoba. He spent two years as a Post-Doctoral fellow at the British Agricultural Research Council research establishment near Bristol, England, followed by a Post- Doctoral fellowship in the Department of Biochemistry at the Hospital for Sick Children. He joined the staff of the Research Institute of the Hospital for Sick Children in 1973, and is currently a Senior Scientist Emeritus in the Molecular Structure and Function Program. From 1995 to 2013 he served as Associate Chief of Research at the Hospital for Sick Children and held the Heart and Stroke Foundation of Ontario/Robert M. Freedom Chair in Cardiovascular Science at the Hospital for Sick Children from 2003 to 2008 and from 2008 to 2013. Dr. Keeley was first cross-appointed to the University of Toronto in 1975, and is currently Professor in the Department of Biochemistry.

Our research interests are in sequence/structure/function relationships in elastomeric proteins such as elastin. This includes studies of the evolutionary history of elastins, regulation of expression of the protein in development and disease, the mechanisms for self-assembly of monomeric elastin into its polymeric form, and the effects of sequence variation, including polymorphisms and splice variants, on the elastomeric properties of the elastin polymer. Our structural studies have led to close collaborations involving computational chemistry, solid state and solution NMR, and bioinformatics. More recently we have compiled and curated a database with comprehensive representation of elastin sequence across the entire phylogenetic range of this protein. This database is being used to identify sequence and collective characteristics of the protein that have been retained over 450 million years of evolution as essential for the functional properties of elastin.

Sequence/Structure/Function Relationships Determining the Elastomeric Properties of Elastin

Elastin is the major structural protein of the large blood vessels, imparting the physical properties of extensibility and elastic recoil that are essential for their physiological function. Our laboratory has had a long-standing interest in the biochemistry of elastin, including its structure/function relationships, its synthesis and assembly in the extracellular matrix and its role in cardiovascular development and diseases such as aneurysms, atherosclerosis and hypertension. Our laboratory has shown that recombinant polypeptides modeled on the elastin monomer are capable of self-assembly into fibrillar structures that can be crosslinked and fabricated into macroscopic materials with elastomeric properties mimicking those of native elastin. This information has been used to deconstruct monomeric elastin in order to determine the contributions of sequence, structure and domain arrangements on elastomeric properties. Recombinant elastomeric materials produced in this way have also been investigated for their possible use as tuneable biomimetic materials for tissue replacement and regeneration. We have also investigated effects of sequence polymorphisms in human monomeric elastin on assembly and material properties of polymeric elastin, and the possible associations of these polymorphisms with reduced durability and increased susceptibility to later-onset pathology affecting vascular and other elastin-rich tissues. Most recently we have assembled a large database of well-curated elastin sequences, extending the phylogenetic range of known elastin sequences to include amphibian, teleost, and elasmobranch elastins, covering the entire breadth of species in which elastins are found. Using this approach, we have identified the important role of repetitive motifs rich in glycine, proline and valine, and other fundamental design features of the protein that are essential for its unusual property of self-assembly and function as an entropic elastomer.

Courses Taught

JCV3063 Advanced Topics in Cardiovascular Sciences- Vascular 

Awards and Distinctions 

2008 - 2013 — Heart and Stroke Foundation of Ontario/Robert M. Freedom Chair in Cardiovascular Science at the Hospital for Sick Children  
1995 - 2013 — Associate Chief, Research Institute, Hospital for Sick Children 
2003 - 2008 — Heart and Stroke Foundation of Ontario/Robert M. Freedom Chair in Cardiovascular Science at the Hospital for Sick Children