Frick Foundation for ALS Research
Frick Foundation for ALS Research
FRICK FOUNDATION FOR ALS RESEARCH
Group 1: Chemical genetic screens for TDP-43 modifiers and ALS therapeutics

Pierre Drapeau, J.Alex Parker & Edor Kabashi, University of Montreal, Quebec, Canada

Pierre Drapeau, B.Sc., Ph.D. (McGill), is a professor and the chair of Pathology and Cell Biology and the Canada Research Chair in Neuroscience at the Université de Montréal. Dr. Drapeau uses the zebrafish as a model to study embryonic development and diseases of the nervous system. Zebrafish lay large numbers of transparent eggs that develop rapidly, its embryo has simple motor behaviours and spinal cord structure, and its genome is sequenced, thus uniquely facilitating the study of spinal cord development in living embryos. Dr. Drapeau is recognised for his research on neural development and synapse formation. Using a comparative genomics approach he is validating mutations of human synaptic genes underlying disorders of the brain and spinal cord.

Dr. Drapeau is a developmental neurophysiologist. He obtained his Ph.D. in biochemistry from McGill University in 1980 for his studies of the kinetics of the sodium-potassium pump, a key regulator of ion gradients and cellular metabolism. He then pursued post-doctoral training in two laboratories. At the University of Maryland in Baltimore, Maryland (1980-82) he studied the mechanism of transmitter release from nerve endings isolated from the mammalian brain. At Stanford University in Palo Alto, California (1982-83) and at the Biozentrum of the University of Basel, Switzerland (1984-85), Dr. Drapeau studied the physiological properties of neurons underlying the modulation of synaptic transmission. This latter work he pursued upon setting up his own lab at McGill University in 1985, where he studied the mechanism of synapse formation between identified neurons. His research led to the first demonstration that single neurotransmitter receptor channels are modulated by protein kinases and to the discovery that tyrosine phosphorylation triggers functional changes during synapse formation.

Since 1996 (at the Université de Montréal since 2006), Dr. Drapeau has been studying the development of the motor network in zebrafish by combining cellular neurophysiology and molecular genetics. He records and images the activity patterns of identified spinal cord and hindbrain neurons in normal and genetically modified embryos. His work has led to the discovery of a novel mechanism of synaptic transmission at fast neuromuscular junctions and the role of synaptic transmitters in promoting neural differentiation during development. The long-term goal of his research is to elucidate the molecular choreography of motor network formation and function. More recently, Dr. Drapeau has discovered that human genes can be expressed in zebrafish, allowing for the validation of mutations in degenerative diseases such as ALS and ataxia and developmental disorders such as autism and schizophrenia. He is collaborating on a large-scale genomics project to identify mutations of synaptic genes related to developmental brain diseases that he is validating in zebrafish embryos. They have discovered that de novo mutations (in patients but not in their parents) are a major cause of autism and schizophrenia.

Dr. Drapeau has garnered national awards for his research, such as scholarships from the FRSQ and MRC/CIHR, a Canada Research Chair in Neuroscience (since 2006) and the 2006 Barbara Turnbull Award for Spinal Cord Research. He has obtained international collaborative awards from the MRC(Canada)-INSERM(France), FRSQ(Canada)-INSERM(France) and the International Human Frontier Science Program. Dr. Drapeau also has extensive teaching experience such as with courses of the International Brain Research Organization and the Marine Biological Laboratory, Woods Hole, MA, where he was a Member of the Corporation from 1991-1997

Alex Parker, B.Sc., Ph.D. (University of British Columbia) is an Assistant Professor in the Department of Pathology and Cell Biology at the Université de Montréal. Dr Parker used the nematode Caenorhabditis elegans to model age-dependent neurodegenerative diseases. Using transgenic invertebrates, like C. elegans, to model human disorders has emerged as a useful strategy in the neurodegeneration field. These studies have led the way to identify new therapeutic targets and strategies usable in patients. The feasibility of a whole-organism approach is enhanced in invertebrates as many pathways affected in neurodegenerative diseases are conserved in a simplified form in these easy-to-use model organisms.

Dr. Parker is a geneticist by training with a focus on late-onset neurodegenerative diseases. He obtained his Ph.D from the University of British Columbia in 2001 for his studies of the huntingtin-interacting protein 1 in the model organism C. elegans. He then pursued training with the Institut National de la Santé et de la Recherche Médicale (INSERM) in Paris , France first as a postdoctoral fellow (2001-2005) and later as an Inserm Young Investigator (2005-2007). In Paris Dr. Parker established a C. elegans model of Huntington’s Disease and investigated the genetic links between aging and neurodegeneration. His research led to the discovery of the sirtuins and their small-molecule regulators as new therapeutic approaches for neurodegenerative diseases. In 2007 Dr. Parker established his own laboratory at the Université de Montréal to better understand the links between the aging process and neurodegeneration. Dr. Parker has expanded his research interests from Huntington’s Disease to model additional protoetoxic diseases including inherited ataxias and ALS. These models are being used to uncover mechanisms and compounds that protect against age-dependent proteotoxicity.

Dr. Parker has won a number of awards for his research including a Hereditary Disease/HighQ Foundation postdoctoral fellowship, an INSERM Young Investigator Award, a FRSQ fellowship and is currently a CIHR New Investigator.

Edor Kabashi completed his Bachelors degree from McGill University in Biology and continued his post-graduate studies at the Montreal Neurological Institute under the supervision of Dr. Heather Durham. During his PhD project, Kabashi studied the role that the ubiquitin-proteasome pathway (the cellular degradation machinery) plays in ALS finding that a decrease of the proteasome activity and its subunit expression occur both in an animal model of ALS as well as in ALS patients.

During his post-doctoral training at the University of Montreal under the direction of Drs. Guy Rouleau and Pierre Drapeau, as the Tim Noel fellow awarded from CIHR and ALS Canada, Dr. Kabashi was the lead author in the discovery of TDP-43 mutations in ALS, and has published a series of articles in very high impact journals.

Dr. Kabashi’s research spans from the discovery of new gene variants in ALS to development of models for these gene mutations using zebrafish. Zebrafish models will be valuable to functionally ascertain whether these gene variants lead to motor neuron deficit/degeneration, further obtaining a better understanding of the molecular pathways of ALS pathogenesis. Further, these models will be helpful in the search for efficacious treatments for this devastating disorder.

Group 2: Tubulin acetylation in motor neuron degeneration: a translational approach

Wim Robberecht and Ludo Van Den Bosch,
Department of Neurology and of Experimental Neurology
University Hospital Leuven, University of Leuven, School of Medicine
Vesalius Research Center, Flanders Institute for Biotechnology

Wim Robberecht obtained his MD from the University of Leuven in Leuven, Belgium, and trained in neurology and neuromuscular diseases at the University Hospital Leuven, the department of Neurology at the University of Virginia, Charlottesville, Virginia, and the Massachusetts General Hospital, Harvard University, Boston, Massachusetts. He obtained his PhD at the department of Pharmacology of the University of Leuven. He currently is Professor of Neurology and chairman of the department of Neurology at the University Hospital in Leuven and directs its Neuromuscular Reference Center. Dr Robberecht is the chairman of the section of Experimental Neurology at the University of Leuven and Group Leader in the Vesalius Research Center of the Flanders’ Institute of Biotechnology at the same University. His main research interest is the epidemiology, genetics, pathogenesis and treatment of amyotrophic lateral sclerosis.

Ludo Van Den Bosch obtained his PhD from the University of Leuven. Thereafter, he became post-doctoral researcher of the ‘Fund for Scientific Research-Flanders’ in the Laboratory of Physiology at the same university. In 1996, he joined the laboratory of Prof. Dr. W. Robberecht (Neurology, University Hospital, K.U.Leuven) and started working on amyotrophic lateral sclerosis (ALS). Since 2002, he is appointed as ‘BOF-ZAP Investigator’ at the University of Leuven in the laboratory of Neurobiology (Vesalius Research Center of the Flanders’ Institute for Biotechnology. His research focuses on different aspects of both ALS and Charcot-Marie-Tooth disease