A5057432844- interferon and immune responses
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Immune Response and Inflammation
- Influenza Virus Research Studies
- Immune Cell Function and Interaction
- Respiratory viral infections research
- CRISPR and Genetic Engineering
- Cerebrospinal fluid and hydrocephalus
- Vaccine Coverage and Hesitancy
- Chromosomal and Genetic Variations
- T-cell and B-cell Immunology
- Herpesvirus Infections and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Tryptophan and brain disorders
- Viral gastroenteritis research and epidemiology
- Circadian rhythm and melatonin
- Immune cells in cancer
- Intracerebral and Subarachnoid Hemorrhage Research
- Endometrial and Cervical Cancer Treatments
- Inhalation and Respiratory Drug Delivery
- RNA and protein synthesis mechanisms
- Plant Virus Research Studies
- Brain Metastases and Treatment
- Liver Diseases and Immunity
Yale University
2008-2024
Dalian University of Technology
2008-2009
Shengli Oilfield Central Hospital
2004
Severe acute respiratory syndrome–coronavirus 2 (SARS-Cov-2) has caused over 13,000,000 cases of coronavirus disease (COVID-19) with a significant fatality rate. Laboratory mice have been the stalwart therapeutic and vaccine development; however, they do not support infection by SARS-CoV-2 due to virus’s inability use mouse orthologue its human entry receptor angiotensin-converting enzyme (hACE2). While hACE2 transgenic pathogenesis, these are currently limited in availability restricted...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has highlighted the need for vaccines that not only prevent disease but also transmission. Parenteral induce robust systemic immunity poor at mucosa. We developed a vaccine strategy we call "prime and spike," which leverages existing generated by primary vaccination (prime) to elicit mucosal immune memory within tract using unadjuvanted intranasal spike boosters (spike). show prime induces resident B T cell responses,...
Influenza A virus (IAV) causes up to half a million deaths worldwide annually, 90% of which occur in older adults. We show that IAV-infected monocytes from humans have impaired antiviral interferon production but retain intact inflammasome responses. To understand the vivo consequence, we used mice expressing functional Mx gene encoding major interferon-induced effector against IAV humans. In Mx1-intact with weakened resistance due deficiencies Mavs and Tlr7, found an elevated respiratory...
Abstract The eye, an anatomical extension of the central nervous system (CNS), exhibits many molecular and cellular parallels to brain. Emerging research demonstrates that changes in brain are often reflected particularly retina 1 . Still, possibility immunological nexus between posterior eye rest CNS tissues remains unexplored. Here, studying immune responses herpes simplex virus brain, we observed intravitreal immunization protects mice against intracranial viral challenge. This protection...
As SARS-CoV-2 continues to cause morbidity and mortality around the world, there is an urgent need for development of effective medical countermeasures. Here, we assessed antiviral capacity a minimal RIG-I agonist, stem-loop RNA 14 (SLR14), in viral control, disease prevention, post-infection therapy, cross-variant protection mouse models infection. A single dose SLR14 prevented infection lower respiratory tract severe type I interferon (IFN-I)–dependent manner. demonstrated remarkable...
As the SARS-CoV-2 pandemic enters its third year, vaccines that not only prevent disease, but also transmission are needed to help reduce global disease burden. Currently approved parenteral induce robust systemic immunity, poor immunity at respiratory mucosa. Here we describe development of a novel vaccine strategy, Prime and Spike, based on unadjuvanted intranasal spike boosting leverages existing generated by primary vaccination elicit mucosal immune memory within tract. We show Spike...
The bile salt export pump (Bsep) represents the major transport system at canalicular membrane of hepatocytes. When examined in model cell lines, genetic mutations BSEP gene impair its targeting and function, contributing to pathogenesis progressive familial intrahepatic cholestasis type II (PFIC II). PFIC are known lead a deficiency human hepatocytes, suggesting that mutants unstable degraded cell. To investigate this further, we have characterized impact several on processing stability rat...
Abstract Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-Cov-2) has caused over 5,000,000 cases of Coronavirus disease (COVID-19) with significant fatality rate. 1–3 Due to the urgency this global pandemic, numerous therapeutic and vaccine trials have begun without customary safety efficacy studies. 4 Laboratory mice been stalwart these types studies; however, they do not support infection by SARS-CoV-2 due inability its spike (S) protein engage mouse ortholog human entry receptor...
Respiratory virus infections in humans cause a broad-spectrum of diseases that result substantial morbidity and mortality annually worldwide. To reduce the global burden respiratory viral diseases, preventative therapeutic interventions are accessible effective urgently needed, especially countries disproportionately affected. Repurposing generic medicine has potential to bring new treatments for infectious patients efficiently equitably. In this study, we found intranasal delivery neomycin,...
Although APOBEC3 proteins are known to be important antiviral restriction factors in both mice and humans, their roles the of endogenous retroviruses (ERV) have been limited vitro studies. Here, we report that human APOBEC3G expressed as a transgene prevents emergence infectious ERV from loci. This study reveals can powerfully restrict active retrotransposons vivo demonstrates how transgenic used investigate host mechanisms inhibit reinforce genomic integrity.
Background The large conductance calcium-activated potassium channel alpha-subunit (Slo) is widely distributed throughout the body and plays an important role in a number of diseases. Prior work has shown that Slo, through its S10 region, interacts with β-catenin, key component cytoskeleton framework Wnt signaling pathway. However, physiological significance this interaction was not clear. Methodology/Principal Findings Using combination proteomic cell biology tools we show existence...
Severe Acute Respiratory Syndrome- Coronavirus 2 (SARS-Cov-2) has caused over 5,000,000 cases of disease (COVID-19) with significant fatality rate.1-3 Due to the urgency this global pandemic, numerous therapeutic and vaccine trials have begun without customary safety efficacy studies.4 Laboratory mice been stalwart these types studies; however, they do not support infection by SARS-CoV-2 due inability its spike (S) protein engage mouse ortholog human entry receptor angiotensin-converting...
As SARS-CoV-2 continues to cause morbidity and mortality around the world, there is an urgent need for development of effective medical countermeasures. Here, we assessed antiviral capacity a minimal RIG-I agonist, stem-loop RNA 14 (SLR14), in viral control, disease prevention, post-infection therapy, cross-variant protection mouse models infection. A single dose SLR14 prevented replication lower respiratory tract severe type I interferon (IFN-I) dependent manner. demonstrated remarkable...
Endogenous retroviruses (ERVs) are genomic sequences that originated from and present in most eukaryotic genomes. Both beneficial detrimental functions attributed to ERVs, but whether ERVs contribute antiviral immunity is not well understood. Here, we used herpes simplex virus type 2 (HSV-2) infection as a model found Toll-like receptor 7 ( Tlr7 -/- ) deficient mice have high systemic levels of infectious protected intravaginal HSV-2 disease, compared wildtype C57BL/6 mice. We deleted the...
Abstract Endogenous retroviruses (ERV) are found throughout vertebrate genomes and failure to silence their activation can have deleterious consequences on the host. Introduction of mutations that subsequently prevent transcription ERV loci is therefore an indispensable cell-intrinsic defense mechanism maintains integrity host genome. Abundant in vitro silico evidence revealed APOBEC3 cytidine-deaminases, including human APOBEC3G (hA3G) potently restrict retrotransposition; yet vivo data...
Abstract Licensed parenteral influenza vaccines induce systemic antibody responses and alleviate disease severity but do not efficiently prevent viral entry transmission due to the lack of local mucosal immune responses. Here, we describe intranasal booster strategy with unadjuvanted recombinant hemagglutinin (HA) following initial mRNA-LNP vaccination, Prime HA. This regimen establishes highly protective HA-specific memory in respiratory tract. Intranasal HA boosters provided significantly...
Abstract Recent studies have revealed that cytosolic nucleic acid-sensing pathways such as cGAS-STING and RIG-I-MAVS are involved in cancer biology. How to employ agents or agonists of these develop new approaches for treatment is a promising direction. In this study, we synthesized unique, binding-specific RIG-I agonist called Stem Loop RNA (SLR) 14 evaluated its vivo anti-tumor efficacy. When tumor volume reached 40–80 mm3, SLR14 was delivered intratumorally, every 2–3 days, total 5–6...
Abstract Endogenous retroviruses (ERVs) are genomic sequences that originated from and present in most eukaryotic genomes. Both beneficial detrimental functions attributed to ERVs, but whether ERVs contribute antiviral immunity is not known. Here we used herpes simplex virus type 2 (HSV-2) infection found mice deficient Toll-like receptor 7 (Tlr7−/−) have high systemic levels of infectious resistant intravaginal HSV-2 compared with wildtype C57BL/6 (B6) mice. We deleted the endogenous...