A5024855537- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Parkinson's Disease Mechanisms and Treatments
- Genetic Neurodegenerative Diseases
- Alzheimer's disease research and treatments
- Prion Diseases and Protein Misfolding
- Nerve injury and regeneration
- RNA regulation and disease
- biodegradable polymer synthesis and properties
- Cholinesterase and Neurodegenerative Diseases
- Immune Cell Function and Interaction
- Neurogenesis and neuroplasticity mechanisms
- T-cell and B-cell Immunology
- RNA Research and Splicing
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer-related molecular mechanisms research
- Ion Channels and Receptors
- CRISPR and Genetic Engineering
- Autophagy in Disease and Therapy
- Pluripotent Stem Cells Research
- Biochemical Acid Research Studies
- Biotin and Related Studies
- Endoplasmic Reticulum Stress and Disease
- Nuclear Structure and Function
- Advanced Neuroimaging Techniques and Applications
University of Southern California
2018-2024
Southern California University for Professional Studies
2024
Broad Center
2019-2023
KU Leuven
2012-2022
VIB-KU Leuven Center for Brain & Disease Research
2012-2018
University of California, Los Angeles
2015-2016
VIB-KU Leuven Center for Microbiology
2013-2015
VIB-KU Leuven Center for Cancer Biology
2013
VIB-VUB Center for Structural Biology
2012
Oligodendrocytes are well known targets for immune-mediated and infectious diseases, have been suggested to play a role in neurodegeneration. Here, we report the involvement of oligodendrocytes their progenitor cells ventral grey matter spinal cord amyotrophic lateral sclerosis, neurodegenerative disease motor neurons. Degenerative changes were abundantly present human patients with sclerosis an mouse model. In model, morphological became apparent before onset, increasingly so during...
The microRNA-29 (miR-29) family is among the most abundantly expressed microRNA in pancreas and liver. Here, we investigated function of miR-29 glucose regulation using miR-29a/b-1 (miR-29a)-deficient mice newly generated miR-29b-2/c (miR-29c)-deficient mice. We observed multiple independent functions family, which can be segregated into a hierarchical physiologic handling. miR-29a, not miR-29c, was to positive regulator insulin secretion vivo, with dysregulation exocytotic machinery...
Amyotrophic lateral sclerosis (ALS) is a fatal degenerative motor neuron disorder of which the progression influenced by several disease-modifying factors. Here, we investigated ELP3, subunit elongator complex that modifies tRNA wobble uridines, as one such ALS disease modifiers. ELP3 attenuated axonopathy mutant SOD1, well C9orf72 zebrafish model. Furthermore, expression in SOD1G93A mouse extended survival and denervation this Depletion vitro reduced modified uridine mcm5s2U increased...
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease with diverse etiologies. Therefore, the identification of common mechanisms and therapeutics targeting these could dramatically improve clinical outcomes. To this end, we developed induced (iMN) models from C9ORF72 sporadic ALS (sALS) patients to identify targets that are effective against types cases, which together comprise ~90% patients. We find iMNs several share two defects - impaired autophagosome formation aberrant...
Abstract Background Amyotrophic Lateral Sclerosis (ALS) is a devastating progressive neurodegenerative disease. Disease pathophysiology complex and not yet fully understood, but proposed to include the accumulation of misfolded proteins, as aggregates are present in spinal cords from ALS patients model organisms. Increasing autophagy hypothesized be protective it removes these aggregates. Rapamycin frequently used increase autophagy, also potent immune suppressor. To properly assess role...
Olmsted syndrome is a rare congenital skin disorder presenting with periorifical hyperkeratotic lesions and mutilating palmoplantar keratoderma, which often associated infections of the keratotic area. A recent study identified de novo mutations causing constitutive activation TRPV3 as cause manifestations syndrome.Genetic, clinical immunological profiling was performed on case patient diagnosis syndrome.The found to harbour previously undescribed 1718G-C transversion in TRPV3, G573A point...
Abstract Schizophrenia is a common complex disorder with polygenic inheritance. Here we show that by using an approach compares the individual loads of rare variants in 1,042 schizophrenia cases and 961 controls, carry increased burden deleterious mutations. At genome-wide level, our results implicate non-synonymous, splice site as well stop-altering single-nucleotide variations occurring at minor allele frequency ≥0.01% population. In independent replication sample 5,585 8,103 controls...
Genetic mutations that cause adult-onset neurodegenerative diseases are often expressed during embryonic stages, but it is unclear whether they alter neurodevelopment and how this might influence disease onset. Here, we show the most common of frontotemporal dementia (FTD) amyotrophic lateral sclerosis (ALS), a repeat expansion in C9ORF72, restricts neural stem cell proliferation reduces cortical thalamic size utero. Surprisingly, expansion-derived dipeptide protein (DPR) not known to reduce...
Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease characterized by the selective death of motor neurons. Disease pathophysiology complex and not yet fully understood. Higher gene expression inositol 1,4,5-trisphosphate receptor 2 (ITPR2), encoding IP3 (IP3R2), was detected in sporadic ALS patients. Here, we demonstrate that IP3R2 also increased spinal cords mice. Moreover, an increase observed other models chronic acute neurodegeneration. Upregulation...
The autoimmune regulator ( A ire), mediates central tolerance of peripheral self. Its activity in thymic epithelial cells TEC s) directs the ectopic expression thousands tissue‐restricted antigens TRAs ), causing deletion autoreactive thymocytes. molecular mechanisms orchestrating breadth transcriptional regulation by ire remain unknown. One prominent model capable explaining both uniquely high number ire‐dependent targets and their specificity posits that tissue‐specific transcription...
Beta-2 microglobulin (β2m) is an essential component of the major histocompatibility complex (MHC) class I proteins and in nervous system β2m predominantly expressed motor neurons. As can promote nerve regeneration, we investigated its potential role amyotrophic lateral sclerosis (ALS) by investigating expression level as well effect genetically removing on disease process mutant superoxide dismutase 1 (SOD1 (G93A) ) mice, a model ALS. We observed strong upregulation neurons during...
Abstract The most common known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is a hexanucleotide repeat expansion (HRE) in C9ORF72 that contributes to neurodegeneration by both loss-of-function (decreased protein levels) gain-of-function (e.g. dipeptide production) mechanisms. Although therapeutics targeting the mechanisms are clinical development, it unclear if these will be efficacious given contribution processes neurodegeneration. Moreover, there lack...