A5014256665- Alzheimer's disease research and treatments
- Supramolecular Self-Assembly in Materials
- Parkinson's Disease Mechanisms and Treatments
- Protein Structure and Dynamics
- Heart Rate Variability and Autonomic Control
- Amino Acid Enzymes and Metabolism
- Skin and Cellular Biology Research
- Prion Diseases and Protein Misfolding
- RNA Research and Splicing
- Wnt/β-catenin signaling in development and cancer
- Botulinum Toxin and Related Neurological Disorders
- Enzyme Structure and Function
Northwestern University
2025
University of California, Los Angeles
2022-2024
Howard Hughes Medical Institute
2022-2024
Abstract Alzheimer’s disease (AD) is the consequence of neuronal death and brain atrophy associated with aggregation protein tau into fibrils. Thus disaggregation fibrils could be a therapeutic approach to AD. The small molecule EGCG, abundant in green tea, has long been known disaggregate other amyloid fibrils, but EGCG poor drug-like properties, failing fully penetrate brain. Here we have cryogenically trapped an intermediate brain-extracted on kinetic pathway EGCG-induced determined its...
Neurodegenerative diseases are characterized by the pathologic accumulation of aggregated proteins. Known as amyloid, these fibrillar aggregates include proteins such tau and amyloid-β (Aβ) in Alzheimer’s disease (AD) alpha-synuclein (αSyn) Parkinson’s (PD). The development spread amyloid fibrils within brain correlates with onset progression, inhibiting formation is a possible route toward therapeutic development. Recent advances have enabled determination fibril structures to atomic-level...
Microbial communities are found throughout the biosphere, from human guts to glaciers, soil activated sludge. Understanding statistical properties of such diverse can pave way elucidate common mechanisms ...Multiple ecological forces act together shape composition microbial communities. Phyloecology approaches—which combine phylogenetic relationships between species with community ecology—have potential disentangle but often ...
Amyloid fibrils of tau are increasingly accepted as a cause neuronal death and brain atrophy in Alzheimer's disease (AD). Diminishing aggregation is promising strategy the search for efficacious AD therapeutics. Previously, our laboratory designed six-residue, nonnatural amino acid inhibitor D-TLKIVW peptide (6-DP), which can prevent vitro. However, it cannot block cell-to-cell transmission aggregation. Here, we find D-TLKIVWC (7-DP), d-cysteine extension 6-DP, not only prevents but also...
Abstract Proteins including FUS, hnRNPA2, and TDP-43 reversibly aggregate into amyloid-like fibrils through interactions of their low-complexity domains (LCDs). Mutations in LCDs can promote irreversible amyloid aggregation disease. We introduce a computational approach to identify mutations disease-associated proteins predicted increase propensity for aggregation. several disease-related the intermediate filament protein keratin-8 (KRT8). Atomic structures wild-type mutant KRT8 segments...
Simple biometrics such as peak heart rate and exercise duration remain core predictors of cardiovascular disease (CVD). Commercial wearable devices track physical cardiac electrical activity. Detailed, longitudinal data collection from wearables presents a valuable opportunity to identify new factors associated with CVD. This cross-sectional study analyzed 6,947 participants in the Fitbit Bring-Your-Own-Device Project, subset All Us Research Program. The primary exposure Daily Heart Rate Per...
The assembly of proteins into fibrillar amyloid structures was once considered to be pathologic and essentially irreversible. Recent studies reveal amyloid-like that form reversibly, derived from protein low-complexity domains which function in cellular metabolism. Here, by comparing atomic-level reversible irreversible fibrils, we find the β-sheets fibrils are enriched flattened (as opposed pleated) formed stacking extended β-strands. Quantum mechanical calculations show glycine residues...