Substances addressing the opioid receptor system are widely used pharmaceuticals for treatment of chronic pain and addictive disorders. Given the difficulties associated with opioid therapy (overdose, tolerance, addiction, respiratory depression and constipation) there is a need for safer narcotic analgesics. Dr. Giguère's research program seeks to use pharmacological, biochemical and structural approaches to develop a new level of understanding of opioid receptor molecular recognition, pharmacological and functional selectivity, drug screening and design of novel functionally selective allosteric modulators of the opioid receptors and GPCR's enhanced tool box by the development of a novel synthetic biology platform and cell-based assay.
The ultimate objective of his research is to generate distinct therapeutics that will uniquely modify their pharmacology in a medically meaningful way increasing their therapeutic efficacy with reduced harmful side effects.
Dr Bennett's Neural Regeneration Laboratory focuses on two complementary research goals. We study the regulation of neural stem cell and progenitor fate by connexin protein family members influencing neuroregeneration and the role of glycerophospholipid neuromodulators in progressive neuronal dysfunction characterizing neurodegenerative disease. The overarching goals are to reduce the rate of neuronal loss associated with brain injury and facilitate cell replacement by mobilizing endogenous progenitor cell populations.
Studying neuro-vascular interactions is essential to gain a better understanding of brain and mind health. Indeed, the brain is highly dependent on a steady supply of blood, which carries oxygen and nutrients, and therefore this noble organ is particularly vulnerable to inherited and acquired cerebrovascular failures. The Lacoste lab investigates 1) how cerebrovascular networks form properly after birth, 2) what mechanisms underlie their plasticity, 3) how their integrity is altered in neurological conditions, and 4) how targeting cerebrovascular remodeling may offer innovative therapeutic options throughout life. Ultimately, identifying key cellular and molecular mediators of cerebrovascular plasticity will lead to important findings about structural and functional determinants of vascular health, an essential pre-requisite for the development of transformative strategies for neuroprotection.
Dr. Lagacé’s lab uses a variety of molecular, cellular, histochemical and behavioral techniques to identify the mechanisms that produce new neurons in the adult brain and to determine their functional role in the healthy and pathological brain. For example, work in the lab is delineating the molecular mechanisms that regulate survival of adult-generated neurons and the crosstalk between autophagy and apoptosis in regulating survival.
Broadly, the Béïque lab is interested in studying synapses, the site of functional connections between neurons in the brain. These tiny structures are highly dynamic in that they can change their function and shape in response to activity. These alterations have been termed “synaptic plasticity” and intense work over many decades has revealed that, in concert with other determinants of cellular excitability, these plasticity mechanisms decisively influence how information is processed and stored in the brain.
Everyone has felt the effect of fatigue in our muscle when we do exercise. For more than a century scientists have tried to elucidate the mechanisms of muscle fatigue. For a long time, changes in metabolites, such as ATP, H + and lactate, were thought to reduce force production by the contractile components and thus be responsible for the decrease in force during fatigue. Surprisingly, recent studies have now demonstrated that neither ATP, H + nor lactate may be responsible for the decrease in force. Even more exciting is the fact that lactate and acidic pH may in fact protect muscle against the fatigue process! As a consequence of these new findings, we must now study how muscle contractility is regulated not only during fatigue but throughout the entire exercise process. This constitutes one of the major research projects in Dr. Renaud laboratory.
John E. Baenziger
The Baenziger lab uses a variety of biophysical tools to study the structure and biological function of a superfamily of proteins, called pentameric ligand-gated ion channels (pLGICs). These neurotransmitter receptors are found in pre-, post-, and non-synaptic membranes of the central and peripheral nervous system where they play a key role in both synaptic communication and information processing. The lab focuses on nicotinic acetylcholine receptors (nAChRs), which respond to the neurotransmitter acetylcholine to mediate synaptic communication. nAChRs are implicated in a number of neurological and neuromuscular disorders, including Parkinson’s and Alzheimer’s disease, mood disorders, epilepsy, addiction, congenital myasthenic syndromes, etc. The Baenziger lab is interested in understanding the mechanistic details of how the activity of nAChRs are modulated during both normal and abnormal brain function, with the goal of developing new strategies to correct the altered synaptic communication that occurs in diseased states.
Dr. Maler’s group conducts basic neuroscience research in two areas using a weekly electric fish model system: experimental and computational analyses of feature extraction by low level sensory systems and experimental and computational analyses of the role of active sensing in spatial learning.
Pierre A. Fortier
Dr. Fortier’s long-term objectives are to understand the mechanisms used by the cerebral cortex for processing information. The nervous system is a large network of neurons that works as a whole but there is a clear division of labour whereby the cerebral cortex has the principal role in the processing of information for perception, planning and voluntary movement in order to adapt to the environment. The most direct method to reveal cortical information processing is to (1) record the activities of input cells to the cortex, (2) follow the flow of information through the network of cortical neurons to the output neurons and (3) record the activities of these output neurons during the behaviour.
Dr. Ruth Slack and her research group’s long term goals are to promote the regeneration of the damaged brain after stroke or in neurodegenerative diseases. She and her team have shown that proteins that regulate cell replication can also play important roles in the regulation of neural stem cell self renewal and long term maintenance in the embryonic and adult brain. Dr. Slack’s group has also shown that mitochondrial dynamics and function have a major impact on adult stem cells and their differentiation, thus changes in metabolism or defects in mitochondrial function in the context of neurodegenerative diseases may have a major impact on neurogenesis, regeneration and neurological function. By exploiting new knowledge of these key regulatory pathways, they plan to activate the neuronal precursor and stem cell pools in order to facilitate regeneration of the damaged brain.
One of the most important unresolved questions in neuroscience is how memories are encoded and stored in the brain. Motor learning differs from other forms of learning, in which repetitive training and practice is required in order to achieve highly skilled and reproducible movements. Our lab employs a novel forelimb lever-press task for head-fixed mice, permitting us to perform chronic structural and functional two-photon imaging in awake and behaving mice. We aim to elucidate the molecular mechanisms underlying learning-driven neural circuit modifications, with spatial precision and cell subtype-specificity, during the formation of new motor memories in the awake brain.
Dr. Ferguson’s research is focused on the functional regulation and activity of G protein-coupled receptors (GPCRs) as a consequence of their interactions with other proteins expressed inside and outside of the cell and how these interactions regulate both normal pathological cell signaling. His current research efforts are primarily focused on the role of metabotropic glutamate receptor signaling in Huntington’s, Alzheimer’s and Parkinson’s disease, the regulation of serotonin receptor activity by corticotrophin releasing factor receptors in response stress with a goal of understanding the effect stress has on anxiety and depression behaviours, as well as understanding the molecular changes in GPCR signaling associated with hypertension.
Woo Jae Kim
In short, the Kim lab is seeking for the fundamental mechanisms how specific neural circuits lead to certain behaviors. We use tiny insect Drosophila melanogaster to answer this question. Dr. Kim has established two behavioral paradigm called ‘Longer-Mating-Duration’ and ‘Shorter-Mating-Duration’. In short term, the Kim lab will focus on identifying functional neural circuits, genetic components, and sensory modality for these behaviors. In mid term, the Kim lab would expand the behavioral repertoires by establishment of automated quantification system of behavior. Beyond this, the Kim lab will establish automated optogenetic & thermogenetic behavioral manipulation system. With the advantage of strong genetic tools available in fruit fly and establishing behavioral quantification and manipulation systems, the Kim lab in the long term will seek for how neural circuits for complex social behavior function in vivo. Reverse engineering to build up eusociality in fruit fly and genomic editing of eusocial insect such as honey bees/ants using CRISPR/Cas9 is also one of the plans to understand social behavior.
Dr. Wang is a neurobiologist whose research focuses on delineating molecular mechanisms that regulate the proliferation and differentiation of neural stem cells, including both embryonic and adult neural stem cells, with the ultimate goal of defining ways to recruit the stem cells that are resident in the brain, and to thereby promote neural repair. Dr. Wang uses stroke as a brain disease model to study whether molecular pathways that regulate the recruitment of neural stem cells under pathological conditions could be modulated and utilized to promote brain repair and stroke recovery.
Dr. Corbett’s current research concerns recovery of sensory-motor and cognitive function following stroke. His lab uses a variety of approaches to enhance neuroplasticity and stroke recovery including novel forms of rehabilitation, exercise and mobilization of endogenous neural precursors and stem cells.
Dr. Albert’s research focuses on the study of major depression and anxiety. His research program aims at understanding the proteins linked to these dreadful diseases using conditional and inducible mouse knockout models. His laboratory addresses the role of specific proteins in the regulation of serotonin in vivo linked to various pathology such as anxiety and depression. In addition, his laboratory has developed and investigated new models of depression, recently showing that chronic stress induces DNA methylation pattern of the 5-HT1A promoter sites that can be reversed by chronic antidepressant treatment. By identifying risk polymorphisms for anxiety, depression and suicide, and defining how they affect gene regulation, his research aims to provide new approaches for better treatment of anxiety and depression.
The Bergeron laboratory is committed to unraveling the role of glutamate in the nervous system, and how this amino acid could play a role in the pathophysiology of neuropsychiatric disorders. Dr. Bergeron’s research focus is also dedicated to investing the roles of glycine and sigma receptor and how they modulate a subtype of glutamate receptor: NMDA receptor. The NMDA receptor is known to be involved in synaptic transmission and plasticity and has been proposed to play a role in the etiology of dementia, schizophrenia, stroke and other neuropsyciatric disorders.
Dr. Chen’s laboratory is working to identify the common molecular links between metabolic disorders (diabetes and atherosclerosis), stroke and anxiety in order to develop common therapies to restore healthy brain function. In addition, patients with schizophrenia and autism often display metabolic syndrome. Signaling pathways affected in metabolic syndrome may be therapeutic targets to improve these two disorders. The techniques used in Dr. Chen’s laboratory include molecular biology, cell culture, optogenetics, in vitro (brain slice) and in vivo electrophysiological recording and pharmacological studies and animal behavioural tests.
Dr. Kothary’s research program is primarily focused on studying the fundamental role of a cytoskeletal linker protein important for intracellular trafficking, investigating extrinsic and intrinsic factors important for oligodendrocyte mediated myelination and remyelination of the CNS, and understanding Spinal muscular Atrophy pathogenesis and identifying novel therapeutics for this devastating children’s disease.
ALS is a progressive neurodegenerative disease caused by death of motor neurons. Cellular processes associated with familial ALS genes are diverse, suggesting the etiology is multifactorial involving multiple biological processes. Dr. Ngsee’s research program focuses on VAPB (VAMP-associated protein B), a gene mutated in an autosomal dominant, slow progressing form of ALS. His recent study showed that mutant VAPB blocks protein trafficking in a membrane compartment derived from the endoplasmic reticulum (ER) called the ER-Golgi intermediate compartment (ERGIC). Mutant VAPB primarily affects retrograde cargo transport from ERGIC. Nuclear envelope proteins also utilize this transport route and loss of VAPB disrupts their delivery that leads to progressive deterioration of the nuclear envelope. The goals are to define the cellular consequences of this nuclear envelope defect, characterize the biological processes affected by the defect at ERGIC that could contribute to motor neuron death, and explore treatment strategies that could mitigate the adverse effects of mutant VAPB.
Research in Dr. Picketts’ laboratory focuses on the role of chromatin remodeling proteins in neural development and intellectual disability disorders. We utilize transgenic mouse models in which genes encoding epigenetic regulators are genetically inactivated to identify their requirement during brain development and to obtain insight into the mechanisms causing intellectual disability. Determining the genes and developmental pathways regulated by these epigenetic regulators is critical for the generation of novel therapeutics for patients.
The goal of the research efforts in the Schlossmacher laboratory is to contribute to the clinical improvement of individuals living with Parkinson Diseases (PD). Specifically, his laboratory seeks to contribute to the development of cause-directed therapies. In doing so, they are focusing on the molecular processes that drive neurodegeneration. Specifically, they are studying the mechanisms by which PD-linked genes (including a-synuclein, Parkin LRRK2 and GBA1) lead to neuronal dysfunction and the pathways that govern their metabolism. His laboratory is also developing better animal models of young- and late-onset PD as well as dementia with Lewy bodies and pursuing our effort to identify novel biomarkers for the diagnosis of PD.
Research in Dr. Tiberi’s laboratory focuses on the elucidation of the molecular and regulatory mechanisms controlling the functionality of a class of proteins called receptors located on the cell surface and to which the brain chemical dopamine attaches and induces their activation. Considering that the impairment in dopamine receptor function is a feature of several neuropsychiatric disorders such as schizophrenia, Parkinson’s disease, Huntington, depression and drug addiction, the work of Dr. Tiberi will shed new lights on novel therapeutic avenues to treat these diseases.
Dr. Eve Tsai is a Neurosurgeon and Clinician Scientist who joined The Ottawa Hospital, the Ottawa Hospital Research Institute and the Faculty of Medicine at the University of Ottawa in 2006. Her main surgical interests focus on all types of spine and spinal cord diseases such as spinal cord injury, spinal cord and spine tumors, syringomyelia, and myelopathy. Her research focuses on spinal cord repair strategies, axonal regeneration, MRI imaging of spinal cord tracts in humans and animals, and clinical outcomes after spine surgery.
Inherited retinal degeneration leads to a progressive loss of vision. Most often, they are characterized by a gradual loss of the photoreceptors in the retina. Cell death occurs through the process of apoptosis. Dr. Tsilfidis’ laboratory uses inhibitors of apoptosis (IAPs) to prevent retinal degeneration in the contexts of diseases such as retinitis pigmentosa, retina ischemia, or Leber’s Hereditary Optic Neuropathy (LHON). Collectively, Dr. Tsilfidis current studies are aimed at developing various therapeutic application to cure human retinal disease.
One of the most important unresolved questions in neuroscience is how memories are encoded and stored in the brain. Motor learning differs from other forms of learning, in which repetitive training and practice is required in order to achieve highly skilled and reproducible movements. Dr. Chen's lab employs a novel forelimb lever-press task for head-fixed mice, permitting them to perform chronic structural and functional two-photon imaging in awake and behaving mice. They aim to elucidate the molecular mechanisms underlying learning-driven neural circuit modifications, with spatial precision and cell subtype-specificity, during the formation of new motor memories in the awake brain.
Human behavior depends on the coordinated development of billions of neurons into functional circuits and networks. This complexity is attained by the intrinsic properties and shapes of neurons and their remarkable ability to find and make successful connections with each other and their target cells. Dr. Colavita’s laboratory uses genetic and molecular approaches in the nematode C. elegans to study neuronal migration, axon guidance, and the underlying mechanisms that allow neurons to acquire and maintain characteristics such as polarized cell shapes and branched morphologies that distinguish them from other cell types. Understanding these processes may ultimately lead to the development of new drug targets or therapies that promote neuronal repair following brain injury or neurodegenerative disease.
Dr. Naud’s research program looks at using mathematical models to study the structure of the neural code in order to develop efficient information algorithms and improve brain machine interfaces. He also designs statistical methods that can be used on multiple types of biomedical data: electrophysiology, multi-electrode arrays, fluorescence imaging. This is done to arrive at a compact and accurate description of neurons and how they interact[SD1] . We use computer stimulation of neural systems in health and disease, allowing us to screen hypotheses at a rate unachievable with experimental methods, enabling us to test recovery protocols in demyelinating diseases and stroke.
Dr. Rousseaux’s research program primarily focuses on neurology, specifically looking at three central research themes; 1) Understanding the role of protein mislocalization in neurodegenerative diseases. 2) Regional vulnerability in neurodegenerative disease and 3) Ascribing medical value to genetic variance in neurodegeneration.
Dr. Silasi’s lab studies rodent models of stroke recovery using optogenetic tools to map the brain, and detailed behavioural measures to assess functional impairments and recovery. The goal of his laboratory is to develop therapeutic brain stimulation paradigms that may be combined with rehabilitation to enhance recovery after adult and neonatal stroke. Specifically, his ongoing projects include the identification of effective stimulation targets following perinatal stroke and the assessment of the functional impact of microinfarcts.
Dr. Bulman’s research interests involve the identification of genes for rare genetic disorders, the translation of these discoveries to the clinic and the implementation of new molecular testing paradigms into newborn screening. The lab uses a variety of genetic technologies from genetic mapping, candidate Sangar sequencing, CGH, exome and whole genome sequencing. His focus is to identify new genes causing Parkinson’s Disease, Brachydactyly A-1, and Myoclonus Dystona.
Dr. Parks’ research interests range from characterizing various aspects of basic adenovirus (Ad) biology to exploring the efficacy of Ad-based vectors for the delivery of therapeutic genes in animal models of genetic or acquired disease. Part of his research is dedicated to improving Ad technology, such as exploring novel methods of producing Ad vectors deleted of all viral protein coding sequences (termed helped-dependent Ad vectors), and investigating methods to achieve cell-type specific infection with Ad.
Dr. Woulfe's research interests center on the role of alpha-synuclein aggregation in the pathophysiology of Parkinson's disease. In collaboration with other OHRI researchers, he is creating a novel mouse model which will allow the direct visualization of alpha-synuclein aggregation in vivo. Moreover, his laboratory is exploring a novel type of intranuclear inclusion body in the normal human brain which may reveal clues to intranuclear inclusion formation in neurodegenerative disease.