Paul Hamel

Paul Hamel is Professor in the Department of Laboratory Medicine & Pathobiology in the faculty of Medicine at the University of Toronto. He received his Ph.D. In Biochemistry at the University of Toronto in 1986 after his B. Sc. in Biochemistry at the University of Ottawa. He has been a member of the Department of Pathology/LMP since 1992.

Research Synopsis

We are interested in the structural aspects of components of the Hedgehog pathway that generate the diversity of cellular responses to the Hedgehog ligands in normal cells, during mammary gland development and in transformed (cancer) cells.

We have had a long-standing interest in studying the role and activities of the essential developmental pathway, the Hedgehog pathway, during mammary gland development. This has lead us to work in two interacting areas.

The first is to understand how Hedgehog-signalling contributes to morphogenesis of the mammary gland during puberty. In this context we are interested further in understanding how this same pathway interacts with other signalling pathways that give rise to cancer in the mammary gland.

This focus stems from a second line of investigation in which we are defining the structural aspects of the receptor of the Hedgehog ligands, called Pathced-1, that give rise to its activities. In particular, we are defining novel pathways that are stimulated by the Hedgehog ligands due to the interaction of components of these alternative pathways to the unique cytoplasmic region of Patched-1 predicted to form an Intrinsically Disordered Protein Region. 

As a final area of investigation, we have begun a collaboration with a number of labs that are defining the role of a related protein, called PtchD1, that plays a role in Autism Spectrum Disorder (ASD) and ADHD. These investigations will define the activities of PtchD1 and how, upon their mutation in humans, ASD/ADHD arises.

Selected Publications

DC Ung, G Iacono, H Méziane, E Blanchard, M-A Papon, M Selten, J-R van Rhijn, R Montjean, J Rucci,S Martin, A Fleet, M-C Birling, S Marouillat, R Roepman, M Selloum, A Lux4, R-A Thépault, P Hamel, K Mittal, JB Vincent, O Dorseuil, HG Stunnenberg, P Billuart, NN Kasri, Y Hérault and F Laumonnier Ptchd1 deficiency induces excitatory synaptic and cognitive dysfunctions in mouse Molecular Psychiatry in press 2017

Fleet A, Lee JP, Tamachi A, Javeed I, Hamel PA. Activities of the Cytoplasmic Domains of Patched-1 Modulate but Are Not Essential for the Regulation of Canonical Hedgehog Signaling. J Biol Chem. 2016 Aug 19;291(34):17557-68.

Okolowsky N, Furth PA, Hamel PA Oestrogen receptor-alpha regulates non-canonical Hedgehog-signalling in the mammary gland. Dev Biol. 2014 Jul 15;391(2):219-29.

Harvey MC, Fleet A, Okolowsky N, Hamel PA. Distinct effects of the mesenchymal dysplasia gene variant of murine Patched-1 protein on canonical and non-canonical Hedgehog signaling pathways. J Biol Chem. 2014 Apr 11;289(15):10939-49.