Lea Harrington
Full Professor, Department of Medicine, Professeure accrédité (cross-appointment), Department of Biochemistry, Université de Montréal, Institute of Research in Immunology and Cancer (IRIC), Montréal, QC, Canada
Visiting Professor, School of Biological Sciences, Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK
Lea Harrington moved to the University of Montreal in 2011 from the University of Edinburgh, where she previously held a Personal Chair as Professor of Telomere Biology and was the Associate Director of Postgraduate M.Sc. Programmes in the School of Biological Sciences. She retains a Visiting Professorship at the University of Edinburgh and is currently a Professor in the Department of Medicine at l’Université de Montréal.
Since starting her group in 1995 (at the Ontario Cancer Institute, where she stayed until 2007), Dr. Harrington and her colleagues have been interested in the mechanisms by which chromosome ends, telomeres, are maintained and protected from degradation and recombination. The activity of an enzyme responsible for new telomere addition in most eukaryotes, telomerase, is increased in many cancers and conversely is decreased in many somatic tissues. Since critically short telomeres that elicit a DNA damage response are incompatible with cell viability, the regulation of telomerase activity and dosage is thus a critical determinant of normal and cancer cell proliferation.
The Harrington laboratory has employed several genetic models to study the dosage-sensitive regulation of telomere homeostasis and its consequences in aging, cancer, and disease. In the single-celled genetic model S. cerevisiae (baker’s yeast), her group conducted genome-wide genetic screens to identify genes whose absence affects survival when telomerase expression is reduced or abrogated. These screens identified a pathway for cell survival that acts independently of telomerase and homologous recombination. Using mammalian genetic models, Dr. Harrington and her group discovered that telomerase is haploinsufficient in mice, and that long telomeres permit the prolonged survival of normal murine and tumorigenic human cells even in the absence of telomere length maintenance.
More recently, her lab uncovered an unexpected ability of short telomeres to perturb the stability cell differentiation, in which quiescent, differentiated cells with critically short telomeres revert to a more stem cell-like state and resume proliferation. These findings suggest that telomere maintenance plays a previously unappreciated role in cell fate, and may prove to be an important mechanism that contributes to the remodeling of tissue function in aging, disease, and cancer.