Dr. Pierre Lavigne

Dr. Pierre Lavigne is an Assistant Professor of Pharmacology in the Faculty of Medicine at l’Université de Sherbrooke since February 2000. He was born in Trois-Rivières, Québec. He obtained his Ph.D. in Molecular Biophysics from the Trois-Rivières Campus of l’Université du Québec. His Ph.D. thesis treated of the hydrophobic interaction, a fundamental energetic determinant for the stability of protein structure and function. His Ph.D. work led to the measurement of the magnitude and further understanding of this critical force and to the development of an experimental approach to measure it. After his Ph.D., he went to the University of Alberta to train in Protein Engineering, Biophysical Chemistry and high-resolution solution state NMR as a Medical Research Council of Canada (MRC) post-doctoral fellow, under the supervision of Drs Robert S. Hodges, Cyril M. Kay and Brian D. Sykes in the Protein Engineering Network of Centres of Excellence. During his post-doctoral training, Dr. Lavigne initiated and developed an exciting research program on the elucidation of the structural determinants regulating the molecular recognition within the Myc/Max/Mad network of transcription factors.

In his laboratory in Sherbrooke, Dr Lavigne is pursuing the elucidation of the structural determinants and molecular mechanism underlying the aberrant control of transcription by the Myc/Max/Mad network in cancer cells. His research program is funded by the Canadian Institutes of Health Research (CIHR, formerly CRM) and focused on the application of an integrated approach using structural, molecular and cellular biology in order to develop anti-c-Myc molecules.

In many cancer cells, the proto-oncogene c-myc is translocated or amplified and promotes the tumorigenesis of these cells. This leads to high levels of c-Myc, the oncoprotein. c-Myc is a B-HLH-LZ transcription factor that can reduce the levels of growth inhibitory proteins and at the same time elevate the levels of proteins that promote the growth and immortalization of the cancer cells. This is the overall mechanism by which c-Myc contributes to tumorigenesis. In more detail, c-Myc plays its roles in tumorigenesis as a heterodimer with another B-HLH-LZ protein called Max. As a c-Myc/Max heterodimer, c-Myc can bind specific DNA sequences and activates the transcription of genes coding for growth promoting signals. The c-Myc/Max heterodimer can also recognize a protein called Miz-1. As a heterocomplex with Miz-1, c-Myc transrepresses the transcription of genes encoding for proteins with growth inhibitory signals. Therefore, molecules that could prevent c-Myc from recognizing Max and Miz-1 as well as preventing c-Myc from binding DNA could have potent anti-cancer activity. Dr. Lavigne’s laboratory is actively involved in the rational development of such molecules and has already shown that mutants of Max that have been engineered for improved dimeric stability can efficiently compete with c-Myc for DNA binding and reduce the transactivation of certain genes. More recently, Dr. Lavigne solved the NMR solution structure of the Max homodimer and clarified the mechanism of DNA binding of this class transcription factor. This information will help to develop more potent Max mutants. Finally, Dr Lavigne is characterizing the molecular recognition of the protein Miz-1 with the c-Myc/Max heterodimeric B-HLH-LZ. All of this information lays the foundation for the development of gene therapy like approaches for cancer treatment and the development of smaller molecules with anticancer therapeutic potential.

Dr. Lavigne is the recipient of a strategic salary grant from the Fonds FCAR (now managed by the Fonds pour la recherche en santé du Québec, FRSQ) and a CFI new opportunity grant from the Canadian Foundation for Innovation (CFI).

For further information, please contact Dr. Pierre Lavigne using the Email contact form or by phone at 819 820-6868 ext 15462