A5020846644- Lysosomal Storage Disorders Research
- Biochemical and Molecular Research
- Cellular transport and secretion
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Carbohydrate Chemistry and Synthesis
- Trypanosoma species research and implications
- RNA and protein synthesis mechanisms
- Supramolecular Self-Assembly in Materials
- Glycosylation and Glycoproteins Research
- Calcium signaling and nucleotide metabolism
- Cardiomyopathy and Myosin Studies
- Pancreatic function and diabetes
- RNA modifications and cancer
- Glycogen Storage Diseases and Myoclonus
- Genomics and Chromatin Dynamics
- Congenital heart defects research
- Cytomegalovirus and herpesvirus research
- Origins and Evolution of Life
- Alzheimer's disease research and treatments
- Adenosine and Purinergic Signaling
- Protein Structure and Dynamics
- Nuclear Receptors and Signaling
- Congenital Heart Disease Studies
Children's Hospital of Orange County
2022-2024
Auburn University
2021
Emory University
2017-2019
Proteinaceous plaques associated with neurodegenerative diseases contain many biopolymers including the polyanions glycosaminoglycans and nucleic acids. Polyanion-induced amyloid fibrillation has been implicated in disease etiology, but structural models for amyloid/nucleic acid co-assemblies remain limited. Here we constrain acid/peptide interactions model peptides that exploit electrostatic complementarity define a novel co-assembly. The structure provides acid/amyloid co-assembly as well...
Infantile-onset Pompe disease (IOPD) results from pathogenic variants in the
Free sialic acid storage disorders (FSASDs) result from pathogenic variations in the SLC17A5 gene, which encodes lysosomal transmembrane protein sialin. Loss or deficiency of sialin impairs FSA transport out lysosome, leading to cellular dysfunction and neurological impairment, with most severe form FSASD resulting death during early childhood. There are currently no therapies for FSASDs. Here, we evaluated efficacy CRISPR-Cas9-mediated homology directed repair (HDR) adenine base editing...
The RNA world hypothesis simplifies the complex biopolymer networks underlining informational and metabolic needs of living systems to a single scaffold. This simplification requires abiotic reaction cascades for construction RNA, this chemistry remains subject active research. Here, we explore complementary approach involving design dynamic peptide capable amplifying encoded chemical information setting stage mutualistic associations with RNA. Peptide conformational are known be evolution...
Pompe disease, an autosomal recessive disorder caused by deficient lysosomal acid α-glucosidase (GAA), is characterized accumulation of intra-lysosomal glycogen in skeletal and oftentimes cardiac muscle. The c.1935C>A (p.Asp645Glu) variant, the most frequent GAA pathogenic mutation people Southern Han Chinese ancestry, causes infantile-onset disease (IOPD), presenting neonatally with severe hypertrophic cardiomyopathy, profound muscle hypotonia, respiratory failure, infantile mortality. We...
Abstract Proteinaceous plaques associated with neurodegenerative diseases contain many biopolymers including the polyanions glycosaminoglycans and nucleic acids. Polyanion‐induced amyloid fibrillation has been implicated in disease etiology, but structural models for amyloid/nucleic acid co‐assemblies remain limited. Here we constrain acid/peptide interactions model peptides that exploit electrostatic complementarity define a novel co‐assembly. The structure provides acid/amyloid co‐assembly...
Pompe disease is an autosomal recessive lysosomal storage caused by pathogenic variants in GAA, which encodes enzyme integral to glycogen catabolism, acid α-glucosidase. Disease-relevant cell lines are necessary evaluate the efficacy of genotype-specific therapies. Dermal fibroblasts from two patients presenting clinically with were reprogrammed induced pluripotent stem cells using Sendai viral method. One patient compound heterozygous for c.258dupC (p.N87QfsX9) frameshift mutation and...
The Central Dogma highlights the mutualistic functions of protein and nucleic acid biopolymers, this synergy appears prominently in membraneless organelles widely distributed throughout prokaryotic eukaryotic organisms alike. Ribonucleoprotein granules (RNPs), which are complex coacervates RNA with proteins, a prime example these membranelles underly multiple essential cellular functions. Inspired by highly dynamic character recent studies that ATP both inhibits templates phase separation...
Abstract Pompe disease (PD) is an autosomal recessive disorder caused by deficient lysosomal acid α-glucosidase (GAA), leading to reduced degradation and subsequent accumulation of intra-lysosomal glycogen in tissues, especially skeletal oftentimes cardiac muscle. The c.1935C>A (p.Asp645Glu) variant the most frequent GAA pathogenic mutation people Taiwanese Southern Chinese ethnicity, causing infantile-onset PD (IOPD), which presents neonatally with severe hypertrophic cardiomyopathy,...
Abstract Pompe disease, an autosomal recessive disorder caused by deficient lysosomal acid α-glucosidase (GAA), is characterized accumulation of intra-lysosomal glycogen in skeletal and oftentimes cardiac muscle. The c.1935C>A (p.Asp645Glu) variant, the most frequent GAA pathogenic mutation people Taiwanese Southern Chinese ethnicity, causes infantile-onset disease (IOPD), presenting neonatally with severe hypertrophic cardiomyopathy, profound muscle hypotonia, respiratory failure,...