A5088987240- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- interferon and immune responses
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- HIV Research and Treatment
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Computational Drug Discovery Methods
- Bacterial Genetics and Biotechnology
- Respiratory viral infections research
- Herpesvirus Infections and Treatments
- Protein Structure and Dynamics
- Viral Infections and Immunology Research
- MicroRNA in disease regulation
- Force Microscopy Techniques and Applications
- Influenza Virus Research Studies
- Advanced Fluorescence Microscopy Techniques
- CRISPR and Genetic Engineering
- Viral gastroenteritis research and epidemiology
- PARP inhibition in cancer therapy
- Photosynthetic Processes and Mechanisms
- Parvovirus B19 Infection Studies
- Biosimilars and Bioanalytical Methods
Sanford Burnham Prebys Medical Discovery Institute
2017-2024
Discovery Institute
2017-2024
Center for Scientific Research and Higher Education at Ensenada
2015-2016
Ensenada Institute of Technology
2016
Howard Hughes Medical Institute
2013-2015
Yale University
2011-2015
Stanford University
2006-2010
European Molecular Biology Laboratory
2002
University of Pennsylvania
2001
Recent studies have profiled the innate immune signatures in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and suggest that cellular responses to viral challenge may affect disease severity. Yet molecular events underlie recognition response SARS-CoV-2 infection remain be elucidated. Here, we find replication induces a delayed interferon (IFN) lung epithelial cells. By screening 16 putative sensors involved sensing of RNA virus infection, found MDA5 LGP2...
Abstract The emergence of novel SARS coronavirus 2 (SARS-CoV-2) in 2019 has triggered an ongoing global pandemic severe pneumonia-like disease designated as (COVID-19). To date, more than 2.1 million confirmed cases and 139,500 deaths have been reported worldwide, there are currently no medical countermeasures available to prevent or treat the disease. As development a vaccine could require at least 12-18 months, typical timeline from hit finding drug registration antiviral is >10 years,...
During miRNA biogenesis, the microprocessor complex (MC), which is composed minimally of Drosha, an RNase III enzyme, and DGCR8, a double-stranded RNA-binding protein, cleaves primary (pri-miRNA) in order to release pre-miRNA stem-loop structure. Using phosphoproteomics, we mapped 23 phosphorylation sites on full-length human DGCR8 expressed insect or mammalian cells. can be phosphorylated by mitogenic ERK/MAPK, indicating that may respond integrate extracellular cues. The expression...
Many viral pathogens target innate sensing cascades and/or cellular transcription factors to suppress antiviral immune responses. Here, we show that the accessory protein U (Vpu) of HIV-1 exerts broad immunosuppressive effects by inhibiting activation factor NF-κB. Global transcriptional profiling infected CD4 +T cells revealed vpu-deficient strains induce substantially stronger responses than respective wild type viruses. Gene set enrichment analyses and cytokine arrays showed Vpu...
The chaperone Hsp90 is required for the correct folding and maturation of certain "client proteins" within all cells. Hsp90-mediated particularly important in cancer cells, because upregulated or mutant oncogenic proteins are often clients. inhibitors thus represent a route to anticancer agents that have potential be active against several different types cancer. Currently, various bind at its ATP-binding site preclinical clinical trials. Some most promising well characterized geldanamycin...
During microRNA (miRNA) biogenesis, the Microprocessor complex (MC), composed minimally of Drosha, an RNaseIII enzyme, and DGCR8, a double-stranded RNA-binding protein, cleaves primary-miRNA (pri-miRNA) to release pre-miRNA stem-loop structure. Size-exclusion chromatography MC, isolated from mammalian cells, suggested multiple copies one or both proteins in complex. However, exact stoichiometry was unknown. Initial experiments that DGCR8 bound pri-miRNA substrates specifically, given Drosha...
Mouse embryonic stem cells (mESCs) deficient for DGCR8, a key component of the microprocessor complex, present strong differentiation defects. However, exact reasons impairing their commitment remain elusive. The analysis newly generated mutant mESCs revealed that DGCR8 is essential exit from pluripotency state. To dissociate canonical versus noncanonical functions we complemented with phosphomutant which restored microRNA levels but did not rescue defect. Integration omics data and RNA...
The Epstein-Barr virus (EBV)-encoded noncoding RNAs EBER1 and EBER2 are highly abundant through all four latency stages of EBV infection (III-II-I-0) have been associated with an oncogenic phenotype when expressed in cell lines cultured vitro. In vivo, EBV-infected B cells derived from freshly isolated lymphocytes show that EBER1/2 deletion does not impair viral latency. Based on published quantitative proteomics data BJAB expressing EBER2, we propose the EBERs, their activation AKT a...
Recent studies profiling the innate immune signatures in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggest that cellular responses to viral challenge impact disease severity. Yet, molecular events underlie recognition and response SARS-CoV-2 infection remains be elucidated. Here, we find replication induces a delayed interferon (IFN) lung epithelial cells. Through survey of putative sensors involved detection RNA virus infection, found MDA5 LGP2...
Influenza A virus (IAV) is a human respiratory pathogen that causes yearly global epidemics, as well sporadic pandemics due to adaptation of pathogenic strains. Efficient replication IAV in different species is, part, dictated by its ability exploit the genetic environment host cell. To investigate tropism cells, we evaluated strains diverse subset epithelial cell lines. HeLa cells were refractory growth H1N1 and H3N2 viruses low-pathogenic avian influenza (LPAI) viruses. Interestingly,...