A5003119386- Ubiquitin and proteasome pathways
- Glycosylation and Glycoproteins Research
- interferon and immune responses
- Bee Products Chemical Analysis
- Chromosomal and Genetic Variations
- Circadian rhythm and melatonin
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- Climate Change and Health Impacts
- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Parkinson's Disease Mechanisms and Treatments
- RNA and protein synthesis mechanisms
- Reproductive tract infections research
- CRISPR and Genetic Engineering
- Plant Virus Research Studies
- COVID-19 epidemiological studies
- Inflammasome and immune disorders
- Reproductive Health and Contraception
Cold Spring Harbor Laboratory
2021-2022
Howard Hughes Medical Institute
2021
Stony Brook School
2021
Stony Brook University
2021
United Health Services
2021
Rockefeller University
2017-2019
Columbia University
2012
The accumulation of Tau into aggregates is associated with key pathological events in frontotemporal lobe degeneration (FTD-Tau) and Alzheimer disease (AD). Recent data have shown that misfolded can be internalized by cells vitro (Frost, B., Jacks, R. L., Diamond, M. I. (2009) J. Biol. Chem. 284, 12845-12852) propagate pathology vivo (Clavaguera, F., Bolmont, T., Crowther, A., Abramowski, D., Frank, S., Probst, Fraser, G., Stalder, A. K., Beibel, M., Staufenbiel, Jucker, Goedert, Tolnay,...
Cyclic GMP-AMP synthase is essential for innate immunity against infection and cellular damage, serving as a sensor of DNA from pathogens or mislocalized self-DNA. Upon binding double-stranded DNA, cyclic synthesizes dinucleotide that initiates an inflammatory response. Mouse studies recapitulate causative mutations in the autoimmune disease Aicardi-Goutières syndrome demonstrate ablating gene abolishes deleterious phenotype. Here, we report discovery class inhibitors identified by...
Abstract Cyclic GMP-AMP synthase (cGAS) is the primary sensor for aberrant intracellular dsDNA producing cyclic dinucleotide cGAMP, a second messenger initiating cytokine production in subsets of myeloid lineage cell types. Therefore, inhibition enzyme cGAS may act anti-inflammatory. Here we report discovery human-cGAS-specific small-molecule inhibitors by high-throughput screening and targeted medicinal chemistry optimization two molecular scaffolds. Lead compounds from one scaffold...
Abstract RNA interference is required for post-transcriptional silencing, but also has additional roles in transcriptional silencing of centromeres and genome stability. However, these have been controversial mammals. Strikingly, we found that Dicer-deficient embryonic stem cells strong proliferation chromosome segregation defects as well increased transcription centromeric satellite repeats, which triggers the interferon response. We conducted a CRISPR-Cas9 genetic screen to restore...
Abstract The innate and adaptive immune response are regulated by biological clocks, circulating lymphocytes lowest at sunrise. Accordingly, severity of disease in mouse models is highly dependent on the time day viral infection. Here, we explore whether circadian immunity contributes significantly to seasonality respiratory viruses, including influenza SARS-CoV-2. Susceptibility-Infection-Recovery-Susceptibility (SIRS) SIRS-derived COVID-19 suggest that local sunrise a better predictor...