A5057319119- interferon and immune responses
- Influenza Virus Research Studies
- Neonatal Respiratory Health Research
- HIV Research and Treatment
- Respiratory viral infections research
- Peptidase Inhibition and Analysis
- SARS-CoV-2 and COVID-19 Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Immune Cell Function and Interaction
- Neuroscience and Neuropharmacology Research
- Diabetes and associated disorders
- COVID-19 Clinical Research Studies
- Immune Response and Inflammation
- Protease and Inhibitor Mechanisms
- Viral gastroenteritis research and epidemiology
- Immune cells in cancer
- Ion channel regulation and function
- Virology and Viral Diseases
- vaccines and immunoinformatics approaches
- Long-Term Effects of COVID-19
- RNA modifications and cancer
- Animal Virus Infections Studies
- Respiratory Support and Mechanisms
- Cell death mechanisms and regulation
- Pulmonary Hypertension Research and Treatments
University of California, Santa Cruz
2023-2025
St. Jude Children's Research Hospital
2016-2024
Merck (Japan)
2024
Merck & Co., Inc., Rahway, NJ, USA (United States)
2024
United States Military Academy
2024
Fred Hutch Cancer Center
2013-2016
University of Washington
2014-2016
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2014-2015
Imperial College London
2000-2002
University College London
2000
Influenza A virus (IAV) activates ZBP1-initiated RIPK3-dependent parallel pathways of necroptosis and apoptosis in infected cells. Although mice deficient both fail to control IAV succumb lethal respiratory infection, RIPK3-mediated by itself can limit IAV, without need for necroptosis. However, whether necroptosis, conventionally considered a fail-safe cell death mechanism apoptosis, restrict IAV—or indeed any virus—in the absence is not known. Here, we use selectively IAV-activated show...
Antibodies (Abs) specific for the V3 loop of HIV-1 gp120 envelope neutralize most tier 1 and many 2 viruses are present in essentially all HIV-infected individuals as well immunized humans animals. Vaccine-induced Abs associated with reduced HIV infection rates affect nature transmitted infected vaccinees, despite fact that is often occluded trimer. Here, we link structural experimental data showing how conformational alterations trimer render exceptionally sensitive to Abs. The experiments...
Abstract Astroviruses are a global cause of pediatric diarrhea, but they largely understudied, and it is unclear how where replicate in the gut. Using an vivo model, here we report that murine astrovirus preferentially infects actively secreting small intestinal goblet cells, specialized epithelial cells maintain mucus barrier. Consequently, virus infection alters production, leading to increase mucus-associated bacteria resistance enteropathogenic E. coli colonization. These studies...
Respiratory tract infection with SARS-CoV-2 results in varying immunopathology underlying COVID-19. We examine cellular, humoral and cytokine responses covering 382 immune components longitudinal blood respiratory samples from hospitalized COVID-19 patients. SARS-CoV-2-specific IgM, IgG, IgA are detected blood, however, receptor-binding domain (RBD)-specific IgM IgG seroconversion is enhanced specimens. neutralization activity correlates RBD-specific levels. Cytokines/chemokines vary between...
Respiratory infections cause significant morbidity and mortality, yet it is unclear why some individuals succumb to severe disease. In patients hospitalized with avian A(H7N9) influenza, we investigated early drivers underpinning fatal Transcriptomics strongly linked oleoyl-acyl-carrier-protein (ACP) hydrolase (OLAH), an enzyme mediating fatty acid production, after hospital admission, persisting until death. Recovered had low OLAH expression throughout hospitalization. High levels were also...
Obesity, and the associated metabolic syndrome, is a risk factor for increased disease severity with variety of infectious agents, including influenza virus. Yet, mechanisms are only partially understood. As number people, particularly children, living obesity continues to rise, it critical understand role host status on pathogenesis. In these studies, we use diet-induced obese ferret model tools demonstrate that, like humans, resulted in notable changes lung microenvironment, leading...
Chimeric simian immunodeficiency virus (SIV)/human (HIV) (SHIV) infection of macaques is commonly used to model HIV type 1 (HIV-1) transmission and pathogenesis in humans. Despite the fact that SHIVs encode SIV antagonists known macaque host restriction factors, these viruses require additional adaptation for replication establish a persistent infection. Additional may be required part because CD4 (mCD4) suboptimal receptor most HIV-1 envelope glycoprotein (Env) variants. This requirement...
HIV superinfection (reinfection) has been reported in several settings, but no study designed and powered to rigorously compare its incidence that of initial infection. Determining whether infection reduces the risk is critical understanding an immune response natural protective. This compares a prospective seroincident cohort high-risk women Mombasa, Kenya. A next-generation sequencing-based pipeline was developed screen 129 for superinfection. Longitudinal plasma samples at <6 months, >2...
The development of mRNA vaccines has increased rapidly since the COVID-19 pandemic. As one critical attributes, understanding lipid nanoparticle (LNP) stability is in vaccine product development. However, correlation between LNPs’ physiochemical characteristics and their potency still remains unclear. lack regulatory guidance on specifications for LNPs also partially due to this underexplored relationship. In study, we performed a three-month study heat-stressed LNP samples. samples were...
Tobacco use during pregnancy has many deleterious health consequences for not only the smoking mother, but also on unborn fetus. Children of mothers are reported to have higher frequency and severity respiratory diseases later in life; however, mechanisms driving this increased vulnerability clearly understood. One potential cause disease susceptibility is an altered immune system, originating epigenetically maladaptive hematopoietic stem cells (HSCs). Here, we show that perinatal nicotine...
Identifying conserved mechanisms used by viruses to delay host innate responses can reveal potential targets for antiviral therapeutics. Here, we investigated coronavirus nonstructural protein 15 (nsp15), which encodes a highly endoribonuclease (EndoU). EndoU functions as an immune antagonist limiting the accumulation of viral replication intermediates that would otherwise be sensed host. Despite being promising target, it has been difficult develop small-molecule inhibitors target active...
Phospholipid scramblase 1 (PLSCR1) is an antiviral interferon-stimulated gene (ISG) that has several known anti-influenza functions such as interfering with viral nuclear import, regulating toll-like receptor (TLR) 9 and potentiating the expression of other ISGs. However, exact mechanisms anti-flu activity PLSCR1 in relation to its compartment enzymatic activity, molecular cellular involved have not been completely explored. Moreover, only limited animal models studied delineate role at...
Phospholipid scramblase 1 (PLSCR1) is an antiviral interferon-stimulated gene (ISG) that has several known anti-influenza functions such as interfering with viral nuclear import, regulating toll-like receptor (TLR) 9 and potentiating the expression of other ISGs. However, exact mechanisms anti-flu activity PLSCR1 in relation to its compartment enzymatic activity, molecular cellular involved have not been completely explored. Moreover, only limited animal models studied delineate role at...