A5027162923- Genetic Neurodegenerative Diseases
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Retinal Development and Disorders
- Neurological disorders and treatments
- RNA and protein synthesis mechanisms
- Virus-based gene therapy research
- Neurogenesis and neuroplasticity mechanisms
- Genetics and Neurodevelopmental Disorders
- Microtubule and mitosis dynamics
- Muscle Physiology and Disorders
- Cellular transport and secretion
- Ubiquitin and proteasome pathways
- Herpesvirus Infections and Treatments
- Mitochondrial Function and Pathology
- Pluripotent Stem Cells Research
- Neuroscience and Neuropharmacology Research
- Biotin and Related Studies
- Endoplasmic Reticulum Stress and Disease
- Nerve injury and regeneration
- Autophagy in Disease and Therapy
- Nuclear Receptors and Signaling
- Nonlinear Dynamics and Pattern Formation
- Signaling Pathways in Disease
- Retinal Diseases and Treatments
Buck Institute for Research on Aging
2019-2023
Massachusetts General Hospital
2018
Nantes Université
2016-2017
Centre Hospitalier Universitaire de Nantes
2016-2017
Inserm
2016-2017
École Normale Supérieure de Lyon
2011
Current disease-modifying therapies for Huntington disease (HD) focus on lowering mutant HTT (huntingtin; mHTT) levels, and the immunosuppressant drug rapamycin is an intriguing therapeutic aging neurological disorders. Rapamycin interacts with FKBP1A/FKBP12 FKBP5/FKBP51, inhibiting MTORC1 complex increasing cellular clearance mechanisms. Whether levels of FKBP (FK506 binding protein) family members are altered in HD models if these proteins potential targets have not been investigated....
Huntington's disease (HD) is a neurodegenerative caused by CAG repeat expansion in the Huntingtin (HTT) gene. The resulting polyglutamine (polyQ) tract alters function of HTT protein. Although expressed different tissues, medium-spiny projection neurons (MSNs) striatum are particularly vulnerable HD. Thus, we sought to define proteome human HD patient-derived MSNs. We differentiated HD72-induced pluripotent stem cells and isogenic controls into MSNs carried out quantitative proteomic...
We previously reported that subretinal injection of AAV2/5 RK.cpde6β allowed long-term preservation photoreceptor function and vision in the rod-cone dysplasia type 1 (rcd1) dog, a large animal model naturally occurring PDE6β deficiency. The present study builds on these earlier findings to provide detailed assessment effects gene therapy spatiotemporal pattern retinal degeneration rcd1 dogs treated at 20 days age. analyzed density distribution layers particular cells 3.5-year-old untreated...
Oncolytic viruses, including herpes simplex viruses (HSVs), are a new class of cancer therapeutic engineered to infect and kill cells while sparing normal tissue. To ensure that oncolytic HSV (oHSV) is safe in the brain, all oHSVs clinical trial for glioma lack γ34.5 genes responsible neurovirulence. However, loss attenuates growth cells. Glioblastoma (GBM) lethal brain tumor heterogeneous contains subpopulation stem cells, termed GBM stem-like (GSCs), likely promote progression recurrence....
Recombinant adeno-associated virus (AAV) has emerged as a promising vector for retinal gene delivery to restore visual function in certain forms of inherited dystrophies. Several studies rodent models have shown that intravitreal injection the AAV2/2 is optimal route efficient ganglion cell (RGC) transduction. However, translation these findings larger species, including humans, complicated by anatomical differences eye, key difference being comparatively smaller volume vitreous chamber...
Abstract The GABAergic medium-size spiny neuron (MSN), the striatal output neuron, may be classified into striosome, also known as patch, and matrix, based on neurochemical differences between two compartments. At this time, little is regarding regulation of development Nr4a1 , primarily described a nuclear receptor/immediate early gene involved in homeostasis dopaminergic system, striosomal marker. Using -overexpressing -null mice, we sought to determine whether necessary and/or sufficient...
Abstract Neurodegenerative diseases (ND) have been linked to the critical process in aging—cellular senescence. However, temporal dynamics of cellular senescence ND conditions is unresolved. Here, we show features develop human Huntington's disease (HD) neural stem cells (NSCs) and medium spiny neurons (MSNs), including increase p16 INK4a , a key inducer We found that HD NSCs reprogram transcriptional targets FOXO3, major cell survival factor able repress senescence, antagonizing expression...
Many diseases are linked to dysregulation of the striatum. Striatal function depends on neuronal compartmentation into striosomes and matrix. projection neurons GABAergic medium spiny (MSNs), subtyped by selective expression receptors, neuropeptides, other gene families. Neurogenesis striosome matrix occurs in separate waves, but factors regulating differentiation largely unidentified. We performed RNA- ATAC-seq sorted cells at postnatal day 3, using Nr4a1 -EGFP reporter mouse. Focusing...
X-linked dystonia-parkinsonism (XDP) is a rare neurodegenerative disease endemic to the Philippines. The genetic cause for XDP an insertion of SINE-VNTR-Alu (SVA)-type retrotransposon within intron 32 TATA-binding protein associated factor 1 (TAF1) that causes alteration TAF1 splicing, partial retention, and decreased transcription. Although expressed in all organs, medium spiny neurons (MSNs) striatum are one cell types most affected XDP. To define how mutations gene lead MSN vulnerability,...
The dysregulation of striatal gene expression and function is linked to multiple diseases, including Huntington's disease (HD), Parkinson's disease, X-linked dystonia-parkinsonism (XDP), addiction, autism, schizophrenia. Striatal medium spiny neurons (MSNs) make up 90% the in striatum are critical motor control. transcription factor, Bcl11b (also known as Ctip2), required for development, but adult MSNs vivo has not been investigated. We conditionally deleted specifically postnatal performed...
PNA-microprobe biosensing platform for label-free impedance-based detection of neurodegenerative repeat expansions.
SUMMARY Huntington’s disease (HD) is a neurodegenerative disorder caused by an expansion of CAG repeats in exon 1 the HTT gene, ultimately resulting generation mutant (mHTT) protein. Although mHTT expressed various tissues, it significantly affects medium spiny neurons (MSNs) striatum, their loss and subsequent motor function impairment HD. While HD symptoms typically emerge midlife, disrupted MSN neurodevelopment has important role. To explore effects on development, we differentiated...
Abstract The basal ganglia, best known for processing information required multiple aspects of movement, is also part a network which regulates reward and cognition. major output nucleus the ganglia striatum, its functions are dependent on neuronal compartmentation, including striosomes matrix, selectively affected in disease. Striatal projection neurons GABAergic medium spiny (MSNs), all share basic molecular signatures but subtyped by selective expression receptors, neuropeptides, other...
Striatal function is dependent on neuronal compartmentation into striosomes and matrix, which are selectively affected in disease. projection neurons GABAergic medium spiny (MSNs), subtyped by selective expression of receptors, neuropeptides, other gene families. Neurogenesis the striosome matrix occurs separate waves, but factors regulating differentiation following migration largely unidentified. We performed RNA- ATAC-seq sorted cells at postnatal day 3 using Nr4a1-EGFP reporter mouse....
On estime aujourd’hui que pres d’un cancer sur cinq a une origine infectieuse. Avec la decouverte de nouveaux agents infectieux, ce chiffre est probablement appele augmenter dans les annees venir. En 2006, nouveau γ-retrovirus des biopsies tumeur prostatique amorca intense recherche : virus, apparente aux retrovirus murins xenotropes et baptise xenotropic MLV-related virus (XMRV), serait-il cause du prostate ? Cinq ans plus tard, l’engouement retrovirologistes retombe. Un un, arguments en...
Viruses represent an important cause of cancer in humans: infections are estimated to account for close one case out five.With the ongoing discovery new infectious agents, this number should be raising near future. In 2006, a _-retrovirus prostate biopsies launched intense research activity: could xenotropic MLV-related virus (XMRV) cancer? Five years later, initial enthusiasm retrovirologists has dramatically diminished. One by one, arguments favouring hypothesis human infection with XMRV...
ABSTRACT Huntington’s disease (HD) is a neurodegenerative caused by CAG repeat expansion in the Huntingtin ( HTT ) gene. The resulting polyglutamine (polyQ) tract alters function of protein. Although expressed different tissues, medium spiny projection neurons (MSNs) striatum are particularly vulnerable HD. Thus, we sought to define proteome human HD patient-derived MSNs. We differentiated HD72 induced pluripotent stem cells and isogenic controls into MSNs carried out quantitative proteomic...
We present a PNA-based microprobe sensing platform to detect nucleic acid repeat mutations by electrochemical impedance spectroscopy. The discriminated Huntington’s disease-associated CAG repeats in cell-derived total RNA. This sensitive, label-free, and PCR-free detection strategy has the potential plethora of length mutation disorders.
We present a PNA-based microprobe sensing platform to detect nucleic acid repeat mutations by electrochemical impedance spectroscopy. The discriminated Huntington’s disease-associated CAG repeats in cell-derived total RNA. This sensitive, label-free, and PCR-free detection strategy has the potential plethora of length mutation disorders.