A5081442391- Genetics, Aging, and Longevity in Model Organisms
- Prion Diseases and Protein Misfolding
- Heat shock proteins research
- Alzheimer's disease research and treatments
- Protein Structure and Dynamics
- RNA Research and Splicing
- Endoplasmic Reticulum Stress and Disease
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Amyotrophic Lateral Sclerosis Research
- Cholesterol and Lipid Metabolism
- Problem and Project Based Learning
- MicroRNA in disease regulation
- Enzyme Structure and Function
- Innovations in Medical Education
- Circular RNAs in diseases
- Peptidase Inhibition and Analysis
- Nanocluster Synthesis and Applications
- Coenzyme Q10 studies and effects
- Veterinary Practice and Education Studies
- Advanced Glycation End Products research
- Neuropeptides and Animal Physiology
- Ubiquitin and proteasome pathways
- Computational Drug Discovery Methods
- Genetic Neurodegenerative Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
2023
National Institutes of Health
2023
University of Pennsylvania
2015-2020
University of Delaware
2013
University of Missouri
2009
Thousands of eukaryotic protein-coding genes are noncanonically spliced to produce circular RNAs. Bioinformatics has indicated that long introns generally flank exons circularize in Drosophila , but the underlying mechanisms by which these RNAs generated largely unknown. Here, using extensive mutagenesis expression plasmids and RNAi screening, we reveal circularization laccase2 gene is regulated both intronic repeats trans -acting splicing factors. Analogous what been observed humans mice,...
Fibrils composed of tau protein are a pathological hallmark several neurodegenerative disorders including Alzheimer's disease (AD). Here we show that when recombinant is seeded with paired helical filaments (PHFs) isolated from AD brain, the amyloid formed shares many structural features PHFs. In contrast, amyloids heparin as an inducing agent-a common biochemical model misfolding-are structurally distinct brain-derived Using ultrastructural analysis by electron microscopy, circular...
The N-terminal acetyltransferase NatA is a heterodimeric complex consisting of catalytic subunit (Naa10/ARD1) and an auxiliary (Naa15). co-translationally acetylates the N termini wide variety nascent polypeptides. In addition, Naa10 can act independently to posttranslationally acetylate distinct set substrates, notably actin. Recent structural studies have also revealed molecular basis for acetylation specificity. Surprisingly, recent reports claim that may lysine residues diverse targets,...
The AAA+ protein disaggregase, Hsp104, increases fitness under stress by reversing stress-induced aggregation. Natural Hsp104 variants might exist with enhanced, selective activity against neurodegenerative disease substrates. However, natural variation remains largely unexplored. Here, we screened a cross-kingdom collection of homologs in yeast proteotoxicity models. Prokaryotic ClpG reduced TDP-43, FUS, and α-synuclein toxicity, whereas prokaryotic ClpB hyperactive were ineffective. We...
Protein misfolding is a recurring phenomenon that cells must manage; otherwise misfolded proteins can aggregate and become toxic should they persist. To counter this burden, have evolved protein quality control (PQC) mechanisms manage proteins. Two classes of systems function in PQC are chaperones aid folding ubiquitin-protein ligases ubiquitinate for proteasomal degradation. How degradative interact coordinate their respective functions not yet fully understood. Previous studies degradation...
ABSTRACT The AAA+ protein disaggregase, Hsp104, increases fitness under stress by reversing stress-induced aggregation. We have engineered potentiated Hsp104 variants to antagonize proteotoxic misfolding linked human neurodegenerative diseases. However, these can exhibit off-target toxicity, which may limit their therapeutic utility. is conserved among all nonmetazoan eukaryotes, raises the possibility that natural might exist with enhanced, selective activity against disease substrates. To...
Misfolded tau is a pathological hallmark of over 20 phenotypically distinct neurodegenerative disorders, including Alzheimer's disease (AD). Researchers are beginning to speculate that misfolded may spread throughout the brain from single locus like prion; whether or not aggregates can cross cell membrane remains unclear. To investigate presence in cerebrospinal fluid (CSF) patients with AD, we developed an amyloid seeding assay for tau. Our findings indicate molecules migrate CSF through...
A retrospective study was performed to evaluate a satisfactory/unsatisfactory (S/U) grading scheme in didactic surgery laboratory during the first 3 years of implementation (2002–2004) and identify areas for improvement that might be adapted this course or similar courses. Each instructor graded six students per session by assigning descriptor very good (G), acceptable (A), unacceptable (U) each 11 assessment categories. U any category one final two laboratories resulted failing grade...
Hsp104 is a hexametric AAA+ protein disaggregase from yeast that can rapidly disassemble disordered aggregates, preamyloid oligomers, amyloids, and prions. These protein‐remodeling activities enable resistance to reversal of stress‐triggered misfolding, have even allowed harness prions for adaptive purposes. orthologues are found in all nonmetazoan eukaryotes eubacteria, but the vast majority these remain unexplored. Thus, sequence space, extent enabled by it, unknown. Here, I present our...