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About Sickkids
About SickKids

Frederick Keeley, PhD

Research Institute
Senior Scientist Emeritus
Molecular Medicine

Associate Chief, Space
Research Institute

University of Toronto
Professor
Department of Biochemistry & Laboratory Medicine and Pathobiology

Other Positions

Robert M. Freedom Chair in Cardiovascular Science
Heart and Stroke Foundation of Ontario
Endowed Chairholder


Phone: 416-813-6704
Fax: 416-813-7480
Email: frederick.keeley@sickkids.ca

Brief Biography

Dr. Fred Keeley, as the Associate Chief (Space) of the Research Institute, directs the allocation, development and utilization review of research space; and leads the space planning and development initiatives for the Research Institute.

Dr. Keeley is a senior scientist in the Cardiovascular Research Program, and is a Professor in the Departments of Biochemistry and Laboratory Medicine and Pathobiology, and a member of the Research Advisory Committee of the Heart and Stroke/Richard Lewar Centre of Excellence at the University of Toronto. He is a former member of the Board of Directors and the Research Policy Committee, and a current member of the Finance Committee of the Heart and Stroke Foundation of Ontario.

Research Interests

  • Regulation of vascular elastin synthesis
  • Polymeric assembly of elastin
  • Design and properties of biomaterials made from recombinantly expressed elastin-like polypeptides

Research Activities

  • Role of hydrophobic domains of elastin in extracellular assembly of the elastic matrix.
  • Self-alignment and polymeric assembly of recombinant human elastin and other elastin-like proteins, with the potential for fabrication of biomaterials with unique and useful physical properties.
  • Sequence/structure/function and evolutionary relationships between elastins and elastin-like proteins in cartilage and other matrix proteins of lower vertebrates and invertebrates.
  • Mechanisms of regulation of aortic elastin synthesis and assembly into the extracellular elastic matrix with normal development and in pathological circumstances (e.g. hypertension, atherosclerosis).
  • Role of transcriptional activity, mRNA stability and efficiency of mRNA translation in regulation of arterial elastin production. Consequences of increased cardiovascular connective tissue protein production in hypertension.

Future Research Interests

  • Mechanisms of post-transcriptional regulation of vascular elastin production in development and disease
  • Mechanisms of self-alignment and self-assembly of elastin and other polymeric, hydrophobic structural proteins

External Funding

  • Canadian Institutes of Health Research
  • Heart and Stroke Foundation of Ontario
  • Natural Sciences and Engineering Research Council

Publications

Cirulis JT, Bellingham CM, Davis EC, Hubmacher D, Reinhardt DP, Mecham RP, Keeley FW. Fibrillins, Fibulins, and Matrix-Associated Glycoprotein Modulate the Kinetics and Morphology of in Vitro Self-Assembly of a Recombinant Elastin-like Polypeptide. Biochemistry. 2008 Oct 31.


He D, Chung M, Chan E, Alleyne T, Ha K, Miao M, Stahl RJ, Keeley FW, Parkinson J. Comparative Genomics of Elastin: Sequence Analysis of a Highly Repetitive Protein. Matrix Biology 26, 524-540, 2007.

Vieth S, Bellingham CM, Keeley FW, Hodge SM, Rousseau D. Microstructural and tensile properties of elastin-based polypeptides crosslinked with genipin and pyrroloquinoline quinone. Biopolymers 85, 199-206, 2007.

Miao M, Bruce AEE, Bhanji T, Davis EC, Keeley FW. Differential expression of two tropoelastin genes in zebrafish. Matrix Biology, 26, 115-124, 2007.

Rauscher S, Baud S, Miao M, Keeley FW, Pomès R. Proline and glycine control protein self-organization into elastomeric or amyloid fibrils. Structure 14, 1667-1676, 2006.

Chung MI, Miao M, Stahl RJ, Chan E, Parkinson J, Keeley FW. Sequences and domain structures of mammalian, avian, amphibian and teleost tropoelastins. Clues to the evolutionary history of elastins. Matrix Biology 25, 492-504, 2006.

Kumashiro KK, Ho JP, Niemczura WP, and Keeley FW. Cooperativity between elastin's hydrophobic and crosslinking domains. J.Biol. Chem. 281, 23757-23765, 2006.

Broekelmann TJ, Kozel BA, Ishibashi H, Werneck CC, Keeley FW, Zhang L, Mecham RP. Tropoelastin interacts with cell-surface glycosaminoglycans via its C-terminal domain. J. Biol. Chem 280, 40939-40947, 2005.

Miao M, Cirulis JT, Lee S, Keeley FW. Structural determinants of crosslinking and hydrophobic domains for self-assembly of elastin-like polypeptides. Biochemistry 44, 14367-375, 2005.

Bellingham CM, Keeley FW. Self-ordered polymerization of elastin-based biomaterials. Current opinion in solid state and materials. Science 8, 135-39, 2004.

Woodhouse KA, Klement P, Chen V, Gorbet MB, Keeley FW, Stahl R, Fromstein JA, Bellingham CM. Investigation of recombinant human elastin polypeptides as non-thrombogenic coatings. Biomaterials 25, 4543-53, 2004.

Miao M, Bellingham CM, Stahl R, Sitarz E, Lane C, Keeley FW. Sequence and structure determinants for the self-aggregation of recombinant polypeptides modeled after human elastin. Journal of Biological Chemistry 278, 48553-48562, 2003.

Bellingham CM, Lillie MA, Gosline JM, Wright GM, Starcher BC, Bailey AJ, Woodhouse KA, Keeley FW. Recombinant human elastin polypeptides self-assemble into biomaterials with elastin-like properties. Biopolymers 70, 445-455, 2003.

Robson P, Wright GM, Youson JH, Keeley FW. The structure and organization of lamprin genes. Multiple copy genes with alternative splicing and convergent evolution with insect structural proteins. Molecular Biology and Evolution 17, 1739-52, 2000.

Hew Y, Grzelczak Z, Lau C, Keeley FW. Identification of a GA-rich sequence as a protein-binding site in the 3'utr of chicken elastin mRNA with a potential role in the developmental regulation of elastin mRNA stability. Journal of Biological Chemistry 275, 24857-64, 2000.

Hew Y, Grzelczak Z, Lau C, Keeley FW. Identification of a large region of secondary structure in the 3'utr of chicken elastin mRNA with implications for the regulation of mRNA stability. Journal of Biological Chemistry 274, 14415-14421, 1999.

Intellectual Property

Self-aligning peptides modeled on human elastin and other fibrous proteins (licensed)