Hugh P.J. Bennett, McGill University

Endocrinology and Metabolism Professor Montreal, Quebec hugh.bennett@mcgill.ca Office: (514) 398-6640

Expert In

Developmental biology Protein structure and function Zebrafish experimental model

Bio/Research

Comparative functional genomics involves the comparison of gene structure and function of homologous genes across species. This discipline has been very successful in identifying cellular mechanisms and biochemical pathways that play critical roles in early embryonic development and tissue growth. Using model organisms (i.e. nematode worm, fruitfly) it has been shown that most of these systems are universally conserved throughout the animal kingdom. When these pathways are absent or inappropriately expressed in humans, they have been shown to be the underlying cause of developmental problems and some cancers. The zebrafish has emerged as a model organism that is expected to define the mechanisms underlying the development of functions unique to vertebrates including humans (i.e. the heart, blood vessels, and advanced nervous and immune systems). We are using the zebrafish to study the function of a new family of tissue growth factors (the granulins) discovered in the Endocrine Laboratory. In mammals, over-expression of the single granulin gene has been shown to contribute to the progression of certain tumours including those of the breast and prostate. In contrast granulin gene under-expression resulting from the loss of one allele has been shown to lead to a form of frontotemporal dementia in human patients. We have shown that in the zebrafish, the granulins are members of a multi-gene family that are critically involved in early embryonic development. Knockdown of granulin gene expression leads to a profound disruption of organ formation including interference in normal development of the central nervous system, internal organs, blood cells and blood vessels. Our research focuses upon defining the mechanism of action of the granulins and ultimately uncovering the role that they play in human biology and the pathophysiology of certain cancers.

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