My Laboratory at the Centre for Molecular Medicine and Therapeutics is dedicated to developing new treatments for hereditary brain diseases, such as Huntington disease, Frontotemporal Dementia, Lou Gehrig’s disease or amyotrophic lateral sclerosis (ALS), and epilepsy. We use the tools of modern molecular biology to generate transgenic animal models and novel cellular models of human disease. New approaches to treatment are then tested in these disease models, with the express goal of accelerating the progress of new treatments for neurodegenerative disorders from the bench to the clinic. The resources and expertise of my laboratory provide the experimental basis for collaborative projects with many scientists world-wide.
Our resources include computational biology support, a full molecular biology laboratory with dedicated cell culture facilities, and histology capabilities. We have a sophisticated mouse behavioral testing unit allowing phenotypic characterization of large numbers of transgenic mice using a standardized behavioral protocol, as well as a dedicated small animal surgical suite allowing a variety of surgical procedures including administration of stem cells, compounds or gene therapy vectors directly into the CNS. I have established a dedicated image analysis suite, stereology system, and automated neuropathology unit for high-throughput quantitative analysis of neurodegeneration in transgenic mouse brains. We currently have an established level II biohazard protocol, and are performing gene therapy experiments using various viral vectors.
In addition to our pre-clinical therapeutic studies, I also have several additional ongoing research projects that are investigating the regulation of the huntingtin gene, the role of wild-type huntingtin in neuronal apoptosis, and a possible role for loss of huntingtin function in neurodegenerative disease. We have developed a mouse model of conditional progranulin deletion. Mutations in the progranulin gene are a common genetic cause of frontotemporal dementia. In addition, new projects include the generation of a mouse model of a genetic form of epilepsy called pyridoxine-dependent epilepsy due to Antiquitin deficiency, and studies of novel disease biomarkers both biochemical (Plasma and CSF) and imaging (MRI and MRS) in HD patients and mouse models.
In addition to my basic research interests, I am a neurologist with an ongoing clinical practice and clinical research program in Huntington disease and related disorders. I am currently the Director of the CMMT Transgenic Animal Facility, the Co-Chair of the Huntington’s study group and a founding Editor-in-Chief of The Journal of Huntington’s Disease