A5081450566- RNA Research and Splicing
- RNA regulation and disease
- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- RNA and protein synthesis mechanisms
- Cholesterol and Lipid Metabolism
- Nuclear Receptors and Signaling
- Lipoproteins and Cardiovascular Health
- Biochemical and Molecular Research
- RNA modifications and cancer
- Cancer therapeutics and mechanisms
- Computational Drug Discovery Methods
- Cellular transport and secretion
Boston University
2020-2024
Broad Institute
2018-2019
Apolipoprotein E receptor 2 (Apoer2) is a synaptic in the brain that binds disease-relevant ligand (Apoe) and highly alternatively spliced. We examined alternative splicing (AS) of conserved Apoer2 exons across vertebrate species identified gain mammals encoding functional domains such as cytoplasmic furin inserts, loss an exon primates eighth LDLa repeat, likely altering surface levels ligand-binding specificity. utilized single molecule, long-read RNA sequencing to profile full-length...
Human apolipoprotein E receptor 2 (APOER2) is a type I transmembrane protein with large extracellular domain (ECD) and short cytoplasmic tail. APOER2-ECD contains several ligand-binding domains (LBDs) that are organized into exons aligning phase junctions, which allows for in-frame exon cassette splicing events. We have identified 25 human APOER2 isoforms from cerebral cortex using gene-specific primers, where the majority exon-skipping events within N-terminal LBD regions compared six in...
Disrupted alternative splicing plays a determinative role in neurological diseases, either as direct cause or driver disease susceptibility. Transcriptomic profiling of aged human postmortem brain samples has uncovered hundreds aberrant mRNA events Alzheimer’s (AD) brains, associating dysregulated RNA with disease. We previously identified complex array combinations across apolipoprotein E receptor 2 ( APOER2 ), transmembrane that interacts both the neuroprotective ligand Reelin and...
SUMMARY Apolipoprotein receptor 2 (APOER2) is an alternatively spliced transmembrane that binds the neuroprotective ligand Reelin and Alzheimer’s disease (AD) related risk factor, APOE. Splicing of single exons in mouse Apoer2 regulates neuronal function synaptic plasticity. However, splicing landscape human APOER2 isoforms physiological AD conditions remains unclear. Here, we identified over 200 unique parietal cortex hippocampus with 151 common between two brain regions. In addition,...
New antibiotics are needed to combat rising resistance, with new Mycobacterium tuberculosis (Mtb) drugs of highest priority. Conventional whole-cell and biochemical antibiotic screens have failed. We developed a novel strategy termed PROSPECT (PRimary screening Of Strains Prioritize Expanded Chemistry Targets) in which we screen compounds against pools strains depleted for essential bacterial targets. engineered targeting 474 Mtb genes screened 100-150 activity-enriched unbiased libraries,...