Dr. Harley Kurata Associate Professor Department of Pharmacology Faculty of Medicine & Dentistry University of Alberta
Regulation of neuronal potassium channels by anti-epileptic drugs and unexpected accessory proteins
Ion channel proteins have evolved to generate electrical signals in response to diverse chemical, physical, or electrical stimuli. These rapid signals underlie our thoughts, movements, and moment-to-moment responses to the environment. It is well understood that disruption of ion channel function in the central nervous system causes a variety of neurological disorders, such as seizures, ataxias, and developmental delay. We are investigating the regulation of neuronal potassium channels with two distinct research themes. Firstly, from an applied pharmacology perspective, we have identified diverse mechanisms of action of a family of compounds that strongly activate neuronal potassium channels called M-channels (Kv7 family). These drugs are in development in a variety of settings for treatment of epilepsy, pain, tinnitus, and other diseases. The second research theme is the identification of accessory proteins that modulate ion channels. Although the identity of most ion channel types is known, they are often studied in isolation, and the effects of disease-linked mutations are not understood in the context of physiological protein complexes. With this general knowledge gap in mind, we have identified multiple previously unrecognized regulatory proteins with powerful effects on channel gating and expression of Kv1.1 and Kv1.2 potassium channels. Variable assembly with these accessory proteins endows Kv channels with behaviors not intrinsic to the channel-forming subunits and often alters the functional outcome of epilepsy-linked mutations in Kv1.2. These findings suggest an expanded view of the molecular diversity of neuronal potassium channels, with important implications for understanding genetic underpinnings of neurological diseases.
Directeur de la recherche / Director of Research Hôpitaux Shriners pour Enfants - Canada / Shriners Hospitals for Children - Canada
Professeur de médecine, chirurgie, et génétique humaine, Université McGill Titulaire, Chaire Francis Glorieux en recherche musculo-squelettique pédiatrique
Professor of Medicine, Surgery, and Human Genetics, McGill University Francis Glorieux Professor of Pediatric Musculoskeletal Research
Role and mechanism of action of 24,25-dihydroxyvitamin D in bone fracture repair
Dr. René St-Arnaud, Ph.D., is the inaugural Francis Glorieux Professor in Pediatric Musculoskeletal Research at McGill University. He is currently Director of Research at Shriners Hospital for Children – Canada in Montreal. He holds cross-appointments as a tenured Professor of Medicine, Surgery, and Human Genetics at McGill University and is an Associate Member of McGill’s Faculty of Dentistry. His research efforts are focussed on vitamin D metabolism as well the control of gene expression in bone-forming cells. His contributions to the understanding of bone cell differentiation and function have been recognized through several distinctions, most recently the C.P. Leblond Career Award. Since the beginning of his career as an independent scientist, Dr. St-Arnaud has supervised over 45 graduate students and postdoctoral trainees. He has a total of 139 peer-reviewed publications and 40 book chapters or conference proceedings. Dr. St-Arnaud holds seven medical invention patents. A respected researcher in the bone field, Dr. St-Arnaud regularly involves himself as a volunteer leader. He chaired the Gordon Conference on Bones & Teeth in 2005 and served as Councilor for the American Society for Bone and Mineral Research (2006-09). He was Director of the Network for Oral and Bone Health Research from 2008 to 2012, President of the Association of Osteobiology (2008-12) and President of Advances in Mineral Metabolism (2011-2013). In 2017, he completed a mandate as Chair of the Canadian Council on Animal Care, the national organization responsible for setting, maintaining, and overseeing the implementation of high standards for animal ethics and care in science throughout Canada.
Wednesday, February 27th, 2019 1:00 - 2:00 pm School of Medicine, Room 132A
Jyh-Yeuan (Eric) Lee, Ph.D. Professeur adjoint / Assistant Professor Biochimie, microbiologie et immunologie / Biochemistry, Microbiology and Immunology Faculté de médecine / Faculty of Medicine, Université d’Ottawa / University of Ottawa
“More than just ABC”
The ATP-binding cassette (ABC) transporters carry out substrate translocation across cell membranes by coupling the energy of ATP binding and/or hydrolysis. While the ATPase domain is highly conserved, recent structural studies of ABC transporters have shown diverse structural folds in the integral transmembrane domains. Our research lies in mechanistic understanding of membrane cholesterol transport by studying the structure-function relationship of ABC transporters. This seminar presentation will includes the following three objectives. 1) I will give an overview of the structural diversity of ABC transporters. 2) Using ABCG5/G8 as the primary model, I will describe the challenge and the findings from studying ABC cholesterol transporters. 3) I will discuss our working model and future directions to investigate membrane cholesterol transport by ABC transporters.