A5036955908- RNA Research and Splicing
- Amyotrophic Lateral Sclerosis Research
- RNA modifications and cancer
- Selenium in Biological Systems
- Cellular transport and secretion
- Lipid metabolism and biosynthesis
- Nanoparticle-Based Drug Delivery
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- Prion Diseases and Protein Misfolding
- Protein Structure and Dynamics
- Enzyme Structure and Function
- Metalloenzymes and iron-sulfur proteins
- Trace Elements in Health
- Folate and B Vitamins Research
- Lysosomal Storage Disorders Research
- Parkinson's Disease Mechanisms and Treatments
- Neurogenetic and Muscular Disorders Research
- Cardiac, Anesthesia and Surgical Outcomes
- ATP Synthase and ATPases Research
- Microtubule and mitosis dynamics
- Global Health and Surgery
- Biochemical and Molecular Research
- Autophagy in Disease and Therapy
- Nerve injury and regeneration
Agilent Technologies (Germany)
2025
University of Illinois Chicago
2014-2024
Saint Louis University
2017-2022
UCLouvain Saint-Louis Brussels
2021-2022
Pediatrics and Genetics
2015
Yale University
2015
Imaging Center
2015
Institute for Molecular Medicine Finland
2015
University of Amsterdam
2015
University of Helsinki
2015
Abstract Background Neuronal uptake and subsequent spread of proteopathic seeds, such as αS (alpha-synuclein), Tau, TDP-43, contribute to neurodegeneration. The cellular machinery participating in this process is poorly understood. One proteinopathy called multisystem (MSP) associated with dominant mutations Valosin Containing Protein (VCP). MSP patients have muscle neuronal degeneration characterized by aggregate pathology that can include αS, Tau TDP-43. Methods We performed a fluorescent...
We aimed to decipher the molecular genetic basis of disease in a cohort children with uniform clinical presentation neonatal irritability, spastic or dystonic quadriplegia, virtually absent psychomotor development, axonal neuropathy, and elevated blood/CSF lactate.We performed whole-exome sequencing blood DNA from index patients. Detected compound heterozygous mutations were confirmed by Sanger sequencing. Structural predictions bacterial activity assay evaluate functional consequences...
The aggregation, cellular mislocalization and dysfunction of TDP-43 are hallmarks multiple neurodegenerative disorders. We find that inducing aggregation through prion-like seeding gradually diminishes normal nuclear localization function. Aggregate-affected cells show signature features loss function, such as DNA damage dysregulated TDP-43-target expression. also observe strong activation TDP-43-controlled cryptic exons in cells, including human neurons treated with proteopathic seeds....
TDP-43, an essential nucleic acid binding protein and splicing regulator, is broadly disrupted in neurodegeneration. TDP-43 nuclear localization function depend on the abundance of its RNA targets recruitment into large ribonucleoprotein complexes, which restricts efflux. To further investigate interplay between nascent RNAs, we aimed to employ 5-ethynyluridine (5EU), a widely used uridine analog for 'click chemistry' labeling newly transcribed RNAs. Surprisingly, 5EU induced accumulation...
Abstract Selenocysteine synthase (SepSecS) catalyzes the terminal reaction of selenocysteine, and is vital for human selenoproteome integrity. Autosomal recessive inheritance mutations in SepSecS–Ala239Thr, Thr325Ser, Tyr334Cys Tyr429*–induced severe, early-onset, neurological disorders distinct populations. Although harboring different mutant alleles, patients presented remarkably similar phenotypes typified by cerebellar cerebral atrophy, seizures, irritability, ataxia, extreme spasticity....
Abstract O-Phosphoseryl-tRNASec selenium transferase (SepSecS) catalyzes the terminal step of selenocysteine (Sec) synthesis in archaea and eukaryotes. How Sec synthetic machinery recognizes discriminates tRNASec from tRNA pool is essential to integrity selenoproteome. Previously, we suggested that SepSecS adopts a competent conformation pre-ordered for catalysis. Herein, using high-resolution X-ray crystallography, visualized tRNA-dependent conformational changes human may be prerequisite...
The evolution of the genetic code to incorporate selenocysteine (Sec) enabled development a selenoproteome in all domains life. O-phosphoseryl-tRNASec selenium transferase (SepSecS) catalyzes terminal reaction Sec synthesis on tRNASec archaea and eukaryotes. Despite harboring four equivalent active sites, human SEPSECS binds no more than two molecules. Though, basis for this asymmetry remains poorly understood. In humans, an acidic, C-terminal, α-helical extension precludes additional...
SUMMARY Uptake and spread of proteopathic seeds, such as αS, Tau, TDP-43, contribute to neurodegeneration. The cellular machinery necessary for this process is poorly understood. Using a genome-wide CRISPR-Cas9 screen, we identified Valosin Containing Protein (VCP) suppressor αS seeding. Dominant mutations in VCP cause multisystem proteinopathy (MSP) with muscle neuronal degeneration. inhibition or disease increase seeding cells neurons. This not associated an seed uptake similar treatment...
ABSTRACT Aggregates of the RNA binding protein TDP-43 are a hallmark amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which neurodegenerative disorders with overlapping clinical, genetic pathological features. Mutations in gene causative ALS, supporting its central role pathogenesis. The process aggregation remains poorly understood whether this includes formation intermediate complexes is unknown. We characterized aggregates derived from purified as function time...
Abstract Background: Neuronal uptake and subsequent spread of proteopathic seeds, such as αS (alpha-synuclein), tau, TDP-43, contribute to neurodegeneration disease progression. The cellular machinery necessary for this process is poorly understood. Methods: Cas9 expressing FRET biosensors were transduced with a whole-genome guide RNA (gRNA) library, seeded fibrils, flow-sorted. Candidate genes protective against seeding identified following gRNA sequencing FRET+ FRET- cell populations....