A5085509204- SARS-CoV-2 and COVID-19 Research
- Mosquito-borne diseases and control
- PARP inhibition in cancer therapy
- Viral Infections and Vectors
- T-cell and B-cell Immunology
- Signaling Pathways in Disease
- interferon and immune responses
- Immune Cell Function and Interaction
- CRISPR and Genetic Engineering
- COVID-19 Clinical Research Studies
- Respiratory viral infections research
- Reproductive System and Pregnancy
- Sirtuins and Resveratrol in Medicine
- Viral gastroenteritis research and epidemiology
- Autophagy in Disease and Therapy
- Genetics, Aging, and Longevity in Model Organisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Invertebrate Immune Response Mechanisms
- Reproductive tract infections research
National Institute of Allergy and Infectious Diseases
2022-2024
National Institutes of Health
2022-2024
National Institute of General Medical Sciences
2024
University of Pennsylvania
2019-2021
There is an urgent need for antivirals to treat the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To identify new candidates, we screen a repurposing library of ∼3,000 drugs. Screening in Vero cells finds few antivirals, while screening human Huh7.5 validates 23 diverse antiviral Extending our studies lung epithelial cells, find that there are major differences drug sensitivity and entry pathways used by SARS-CoV-2 these cells. Entry Calu-3 pH independent...
Abstract There are an urgent need for antivirals to treat the newly emerged SARS-CoV-2. To identify new candidates we screened a repurposing library of ~3,000 drugs. Screening in Vero cells found few antivirals, while screening human Huh7.5 validated 23 diverse antiviral Extending our studies lung epithelial cells, that there major differences drug sensitivity and entry pathways used by SARS-CoV-2 these cells. Entry Calu-3 is pH-independent requires TMPRSS2, low pH triggering acid-dependent...
The novel coronavirus SARS-CoV-2 emerged in China at the end of 2019 and rapidly became a global pandemic. While there are variety experimental treatments currently clinical trials, is dearth approved therapeutics to treat COVID-19. Drug repurposing identifies existing that have already been through testing humans for new indications, particularly advantageous since they could be readily deployed. To this end, we screened library ~3,000 drugs their antiviral activity against cell-based...
All organisms sense and respond to pathogenic challenge. Tissue-specific responses are required combat pathogens infecting distinct cell types. Cyclic dinucleotides (CDNs) produced endogenously downstream of pathogen recognition or by themselves which bind STING activate NF-kB-dependent antimicrobial gene expression programs. It remains unknown whether there immune CDNs in Drosophila tissues. Here, we investigated tissue specific CDN-STING uncovered differences gene-induction patterns across...
Enteric pathogens overcome barrier immunity within the intestinal environment that includes endogenous flora. The microbiota produces diverse ligands, and full spectrum of microbial products are sensed by epithelium prime protective is unknown. Using Drosophila, we find gut presents a high to infection, which partially due signals from microbiota, as loss enhances oral viral infection. We report cyclic dinucleotide (CDN) feeding sufficient protect microbiota-deficient flies enhanced...
Arthropod-borne viruses are diverse pathogens and associated with human disease. Through high-throughput drug screening, we found that sirtuin inhibitors potently antiviral against arboviruses, including flaviviruses such as West Nile virus, bunyaviruses Rift Valley fever alphaviruses chikungunya virus. Sirtuin block infection of these in multiple cell types. Moreover, arrest downstream entry but they do so at an early step, preventing the accumulation viral RNA protein. Since infect vector...
Abstract Maintenance of tissue integrity is a requirement host survival. This mandate prime importance at barrier sites that are constitutively exposed to the environment. Here, we show exposure skin non-inflammatory xenobiotics promotes repair; more specifically, mild detergent reactivation defined retroelements leading induction retroelement-specific CD8 + T cells. These cell responses Langerhans dependent and establish residency within skin. Upon injury, cells significantly accelerate...
Abstract The female reproductive tract (FRT) is a unique barrier site. It tolerates foreign entities like sperm and the fetus for reproduction but must also be immunologically active enough to control pathogens, viruses. Millions of women use antibiotics or anti-retrovirals, these treatments alter environment FRT by changing microbiota inhibiting endogenous retroviruses, impact this on immunity function are understudied. Human cohort data has revealed that vaginal profoundly influences risk...