Janelle Drouin-Ouellet

Janelle Drouin-Ouellet
Université de Montréal | UdeM · Faculty of Pharmacy

PhD in Neurobiology

About

66
Publications
14,599
Reads
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1,831
Citations
Additional affiliations
July 2018 - present
Université de Montréal
Position
  • Professor (Assistant)
January 2015 - present
Lund University
Position
  • PostDoc Position
January 2013 - January 2015
University of Cambridge
Position
  • PostDoc Position

Publications

Publications (66)
Article
Huntington's disease (HD) is a neurodegenerative disorder caused by CAG expansions in the huntingtin (HTT) gene. Modelling Huntington's disease is challenging, as rodent and cellular models poorly recapitulate the disease as seen in aging humans. To address this, we generated induced neurons (iNs) through direct reprogramming of human skin fibrobla...
Article
Full-text available
Direct reprogramming is an appealing strategy to generate neurons from a somatic cell by forced expression of transcription factors. The generated neurons can be used for both cell replacement strategies and disease modelling. Using this technique, previous studies have shown that γ-aminobutyric acid (GABA) expressing interneurons can be generated...
Chapter
Since the first demonstration of direct dopaminergic neuronal reprogramming, over a dozen methods have been developed to generate induced dopaminergic neurons from various sources of cells. Here, we first present an overview of the different methods to generate induced neurons of a generic type and of different subtypes, with a particular focus on...
Article
Full-text available
Rostrocaudal patterning of the neural tube is a defining event in vertebrate brain development. This process is driven by morphogen gradients which specify the fate of neural progenitor cells, leading to the partitioning of the tube. Although this is extensively studied experimentally, an integrated view of the genetic circuitry is lacking. Here, w...
Preprint
Full-text available
Understanding the pathophysiology of Parkinson’s disease has been hampered by the lack of models that recapitulate all the critical factors underlying its development. Here, we generated functional induced dopaminergic neurons (iDANs) that were directly reprogrammed from adult human dermal fibroblasts of patients with idiopathic Parkinson’s disease...
Preprint
Full-text available
Huntington's disease (HD) is a neurodegenerative disorder caused by CAG expansions in the huntingtin (HTT) gene. Modelling HD has remained challenging, as rodent and cellular models poorly recapitulate the disease. To address this, we generated induced neurons (iNs) through direct reprogramming of human skin fibroblasts, which retain age-dependent...
Article
Full-text available
The direct reprogramming of adult skin fibroblasts to neurons is thought to be controlled by a small set of interacting gene regulators. Here, we investigate how the interaction dynamics between these regulating factors coordinate cellular decision making in direct neuronal reprogramming. We put forward a quantitative model of the governing gene re...
Article
The parenteral administration of protein therapeutics is increasingly gaining importance for the treatment of human diseases. However, the presence of practically impermeable blood–brain barriers greatly restricts access of such pharmaceutics to the brain. Treating brain disorders with proteins thus remains a great challenge, and the slow clinical...
Preprint
Full-text available
The rostrocaudal patterning of the neural tube is a key event in early brain development. This process is mainly driven by a gradient of WNT, which defines the fate of the present neural progenitor cells in a dose dependent matter and leads to a subdivision of the tube into forebrain, midbrain and hindbrain. Although this process is extensively stu...
Preprint
Full-text available
The direct reprogramming of adult skin fibroblasts to neurons is thought to be controlled by a small set of interacting gene regulators. Here, we investigate how the interaction dynamics between these regulating factors coordinate cellular decision making in direct neuronal reprogramming. We put forward a quantitative model of the governing gene re...
Article
Full-text available
Background: Genetic, biologic and clinical data suggest that Parkinson’s disease (PD) is an umbrella for multiple disorders with clinical and pathological overlap, yet with different underlying mechanisms. To better understand these and to move towards neuroprotective treatment, we have established the Quebec Parkinson Network (QPN), an open-access...
Article
Full-text available
Direct neural reprogramming can be achieved using different approaches: by expressing neuronal transcription factors, or microRNAs; and by knocking down neuronal repressive elements. However, there still exists a high variability in terms of the quality and maturity of the induced neurons (iNs) obtained, depending on the reprogramming strategy empl...
Article
Full-text available
This review describes the history, development and evolution of cell‐based replacement therapy for Parkinson's disease (PD), from the first pioneering trials with fetal ventral midbrain progenitors to future trials using stem cells as well as reprogrammed cells. In the spirt of Tom Isaacs, the review takes parallels to the storyline of Star Wars, i...
Article
Background: Recently, the development of Parkinson’s disease (PD) has been linked to a number of genetic risk factors, of which the most common is glucocerebrosidase (GBA) mutations. Methods: We investigated PD and Gaucher Disease (GD) patient derived skin fibroblasts using biochemistry assays. Results: PD patient derived skin fibroblasts have norm...
Article
Full-text available
Background: Recently, the development of Parkinson’s disease (PD) has been linked to a number of genetic risk factors, of which the most common is glucocerebrosidase (GBA) mutations. Methods: We investigated PD and Gaucher Disease (GD) patient derived skin fibroblasts using biochemistry assays. Results: PD patient derived skin fibroblasts have norm...
Data
Figure 1A. GCase assay raw data and statistics. Figure 1B. α-galactosidase assay raw data and statistics. Figure 1C. Hexominidase assay raw data and statistics. Figure 1D. Mannosidase assay raw data and statistics. Figure 1E. Western blot GCase raw data, blots and statistics. Figure 1F. Immunocytochemistry fibroblasts were stained for GCase (g...
Data
Figure 2A. Western blots for autophagy assay with iPD, PD GBA, PD/GD and control. Figure 2B. Western blots for autophagy assay with GD. Figure 2C. Autophagy assay statistics.
Article
Full-text available
Induced neurons (iNs), the product of somatic cells directly converted to neurons, are a way to obtain patient-derived neurons from tissue that is easily accessible. Through this route, mature neurons can be obtained in a matter of a few weeks. Here, we describe a straightforward and rapid one-step protocol to obtain iNs from dermal fibroblasts obt...
Article
Full-text available
Direct neuronal reprogramming, by which a neuron is formed via direct conversion from a somatic cell without going through a pluripotent intermediate stage, allows for the possibility of generating patient-derived neurons. A unique feature of these so-called induced neurons (iNs) is the potential to maintain aging and epigenetic signatures of the d...
Article
Full-text available
Background: Recently, the development of Parkinson's disease (PD) has been linked to a number of genetic risk factors, of which the most common is glucocerebrosidase (GBA) mutations.Methods:We investigated PD and Gaucher Disease (GD) patient derived skin fibroblasts using biochemistry assays.Results:PD patient derived skin fibroblasts have normal g...
Article
Full-text available
Direct neuronal reprogramming, by which a neuron is formed via direct conversion from a somatic cell without going through a pluripotent intermediate stage, allows for the possibility of generating patient-derived neurons. A unique feature of these so-called induced neurons (iNs) is the potential to maintain aging and epigenetic signatures of the d...
Article
Full-text available
Direct conversion of human fibroblasts into mature and functional neurons, termed induced neurons (iNs), was achieved for the first time 6 years ago. This technology offers a promising shortcut for obtaining patient- and disease-specific neurons for disease modeling, drug screening, and other biomedical applications. However, fibroblasts from adult...
Article
The adult brain has a very limited capacity for generation of new neurons, and neurogenesis only takes place in restricted regions. Some evidence for neurogenesis after injury has been reported, but few, if any, neurons are replaced after brain injury or degeneration, and the permanent loss of neurons leads to long-term disability and loss of brain...
Article
Full-text available
Glycogen synthase kinase-3β (GSK-3β) has emerged as a critical factor in several pathways involved in hippocampal neuronal maintenance and function. In Huntington's disease (HD), there are early hippocampal deficits both in patients and transgenic mouse models, which prompted us to investigate whether disease-specific changes in GSK-3β expression m...
Article
The sharp rise in the incidence of Alzheimer’s disease (AD) at an old age coincides with a reduction in energy metabolism and core body temperature. We found that the 3xTg-AD mouse model of AD spontaneously develops a lower basal body temperature and is more vulnerable to a cold environment compared to age-matched controls. This was despite higher...
Article
Parkinson disease (PD) is characterized by loss of the A9 nigral neurons that provide dopaminergic innervation to the striatum. This discovery led to the successful instigation of dopaminergic drug treatments in the 1960s, although these drugs were soon recognized to lose some of their efficacy and generate their own adverse effects over time. Desp...
Article
The neuroprotective properties of cystamine identified in pre-clinical studies have fast-tracked this compound to clinical trials in Huntington's disease, showing tolerability and benefits on motor symptoms. We tested whether cystamine could have such properties in a Parkinson's disease murine model and now provide evidence that it can not only pre...
Article
Full-text available
Huntington's disease is a neurodegenerative disorder caused by an abnormal CAG repeat expansion within exon 1 of the huntingtin gene HTT. While several genetic modifiers, distinct from the Huntington's disease locus itself, have been identified as being linked to the clinical expression and progression of Huntington's disease, the exact molecular m...
Article
Objective Although the underlying cause of Huntington's disease (HD) is well established, the actual pathophysiological processes involved remain to be fully elucidated. In other proteinopathies such as Alzheimer's and Parkinson's diseases, there is evidence for impairments of the cerebral vasculature as well as the blood–brain barrier (BBB), which...
Article
Full-text available
Huntington’s disease (HD) is an incurable, inherited, progressive neurodegenerative disorder that is defined by a combination of motor, cognitive and psychiatric features. Pre-clinical and clinical studies have demonstrated an important role for the dopamine (DA) system in HD with dopaminergic dysfunction at the level of both DA release and DA rece...
Article
Full-text available
Deep brain stimulation (DBS) is used to treat a number of neurological conditions and is currently being tested to intervene in neuropsychiatric conditions. However, a better understanding of how it works would ensure that side effects could be minimized and benefits optimized. We have thus developed a unique murine device to perform brain stimulat...
Article
Full-text available
Accumulating evidence supports a role for the immune system in the pathogenesis of Parkinson's disease (PD). Importantly, recent preclinical studies are now suggesting a specific contribution of inflammation to the α-synuclein (αSyn) induced pathology seen in this condition. We used flow cytometry and western blots to detect toll-like receptor (TLR...
Article
Full-text available
Effective approaches to neuropsychiatric disorders require detailed understanding of the cellular composition and circuitry of the complex mammalian brain. Here, we present a paradigm for deconstructing the diversity of neurons defined by a specific neurotransmitter using a microfluidic dynamic array to simultaneously evaluate the expression of 96...
Article
SUMMARY Cell-based therapies for Parkinson's and Huntington's disease have provided mixed clinical outcomes and one of the reasons underlying this is the use of primary fetal tissue as the source of grafted cells. An alternate source of cells, such as stem cells, could overcome many of the issues associated with primary fetal tissue and would help...
Article
Although the concept of cell-based therapy for Parkinson's disease has been around for more than three decades with proof-of-concept studies in man having been achieved, it still remains a controversial experimental therapy. In this review, we discuss the reasons for this and the challenges that this approach generates in the treatment of Parkinson...
Article
Full-text available
Intravenous immunoglobulin (IVIg) is currently evaluated in clinical trials for the treatment of various disorders of the central nervous system. To assess its capacity to reach central therapeutic targets, the brain bioavailability of IVIg must be determined. We thus quantified the passage of IVIg through the blood-brain barrier (BBB) of C57Bl/6 m...
Article
Full-text available
The classic view of unidirectional differentiation has been challenged by the generation of induced pluripotent stem (iPS) cells using transcription-based reprogramming of somatic cells and then redirecting them to virtually any cell type, as well as the more recent development of directly converting cells between somatic lineages [1,2]. This has l...
Article
Full-text available
Technologies allowing for the derivation of patient-specific neurons from somatic cells are emerging as powerful in vitro tools to investigate the intrinsic cellular pathological behaviours of the diseases that affect these patients. While the use of patient-derived neurons to model Parkinson’s disease (PD) has only just begun, these approaches hav...
Article
Full-text available
Intravenous immunoglobulin (IVIg) is a blood-derived product, used for the treatment of immunodeficiency and autoimmune diseases. Since a range of immunotherapies have recently been proposed as a therapeutic strategy for Parkinson's disease (PD), we investigated the effects of an IVIg treatment in a neurotoxin-induced animal model of PD. Mice recei...
Article
Toll-like receptors (TLRs) play a crucial role in innate immunity by recognizing conserved motifs predominantly found in microorganisms. Increasing evidence supports a role for TLRs in sterile inflammation as observed in neurodegenerative disorders. This includes work suggesting a contribution for these receptors to the pathophysiology of Alzheimer...
Article
The myeloid differentiation primary response gene 88 (MyD88) product is the most common adaptor protein implicated in Toll-like and interleukin receptor (TIR) domain signaling and thus plays an important role in the innate immune system. Despite the fact that the MyD88-dependent pathway has emerged as an important player in cell death processes des...
Article
Full-text available
Mounting evidence supports a significant role of inflammation in Parkinson's disease (PD) pathophysiology, with several inflammatory pathways being suggested as playing a role in the dopaminergic degeneration seen in humans and animal models of the disease. These include tumor necrosis factor, prostaglandins and oxidative-related stress components....
Article
A growing body of evidence supports a role of inflammation in the loss of central nervous system neurons both to acute and chronic insults, while its contribution to the loss of neurons in the enteric nervous system remains largely uninvestigated. We have addressed this issue by exploring the role of inflammation in dopaminergic (DAergic) myenteric...
Article
It has been hypothesized that neuroinflammation triggered during brain development can alter brain functions later in life. We investigated the contribution of inflammation to the alteration of normal brain circuitries in the context of neuroexcitotoxicity following neonatal ventral hippocampal lesions in rats with ibotenic acid, an NMDA glutamate...
Article
Parkinson's disease (PD) is a common neurodegenerative disorder largely of idiopathic nature with the exceptions of rare familial forms, and is characterized by both motor and non-motor disturbances. Pathologically, most motor features are the result of a dramatic loss of ventral tier mesencephalic dopaminergic neurons and thus dopamine content at...

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