A5002244469- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- vaccines and immunoinformatics approaches
- Viral Infections and Vectors
- Respiratory viral infections research
- Viral Infections and Outbreaks Research
- CRISPR and Genetic Engineering
- Computational Drug Discovery Methods
- HIV Research and Treatment
- Bacteriophages and microbial interactions
- Mosquito-borne diseases and control
- HIV/AIDS drug development and treatment
- Protein Structure and Dynamics
- Influenza Virus Research Studies
- Immunotherapy and Immune Responses
- SARS-CoV-2 detection and testing
- Complement system in diseases
- Advanced biosensing and bioanalysis techniques
- COVID-19 Impact on Reproduction
- Biomedical and Engineering Education
- Hepatitis B Virus Studies
- Ethics and Legal Issues in Pediatric Healthcare
- interferon and immune responses
- Inhalation and Respiratory Drug Delivery
- RNA Interference and Gene Delivery
Sandia National Laboratories California
2013-2025
Duke University
2023
Sandia National Laboratories
2019-2021
Lawrence Livermore National Security
2019
Washington University in St. Louis
2007-2010
Abstract Engineered monoclonal antibodies have proven to be highly effective therapeutics in recent viral outbreaks. However, despite technical advancements, an ability rapidly adapt or increase antibody affinity and by extension, therapeutic efficacy, has yet fully realized. We endeavored stand‐up such a pipeline using molecular modeling combined with experimental library screening the of F5, potent neutralizing activity against Venezuelan Equine Encephalitis Virus (VEEV), recombinant VEEV...
Entry of human immunodeficiency virus type 1 (HIV-1) commences with binding the envelope glycoprotein (Env) to receptor CD4, and one two coreceptors, CXCR4 or CCR5. Env-mediated signaling through coreceptor results in Galphaq-mediated Rac activation actin cytoskeleton rearrangements necessary for fusion. Guanine nucleotide exchange factors (GEFs) activate regulate its downstream protein effectors. In this study we show that Env-induced is mediated by GEF Tiam-1, which associates adaptor...
ABSTRACT Rift Valley fever virus (RVFV) is a zoonotic pathogen capable of causing serious morbidity and mortality in both humans livestock. The lack efficient countermeasure strategies, the potential for dispersion into new regions, pathogenesis livestock make RVFV public health concern. receptors, cellular factors, entry pathways used by other members family Bunyaviridae remain largely uncharacterized. Here we provide evidence that strain MP-12 uses dynamin-dependent caveola-mediated...
The COVID-19 pandemic underscored the promise of monoclonal antibody-based prophylactic and therapeutic drugs
Binding of human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) with the primary receptor CD4 and one two coreceptors, CXCR4 or CCR5, activates a signaling cascade resulting in Rac-1 GTPase activation stimulation actin cytoskeletal reorganizations critical for HIV-1-mediated membrane fusion. The mechanism by which HIV-1 Env induces subsequent cytoskeleton rearrangement is unknown. In this study, we show that Env-mediated dependent on Galpha(q) its downstream targets....
Paramyxoviruses initiate entry through the concerted action of tetrameric attachment glycoprotein (HN, H, or G) and trimeric fusion (F). The ectodomains HN/H/G contain a stalk region important for oligomeric stability F triggering resulting in membrane fusion. Paramyxovirus HN, G form dimer-of-dimers consisting disulfide-linked dimers their domain cysteines. protein highly pathogenic Nipah virus (NiV) contains distinct but uncharacterized cluster three cysteine residues (C146, C158, C162)....
The development of specific, safe, and potent monoclonal antibodies (Abs) has led to novel therapeutic options for infectious disease. In addition preventing viral infection through neutralization, Abs can clear infected cells induce immunomodulatory functions engagement their crystallizable fragment (Fc) with complement proteins Fc receptors on immune cells. Little is known about the role effector neutralizing in context encephalitic alphavirus infection. To determine function efficacy...
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to persist, demonstrating the risks posed by emerging infectious diseases national security, public health, and economy. Development of new vaccines antibodies for viral threats requires substantial resources time, traditional development platforms are often too slow combat continuously evolving immunological escape variants, reducing their efficacy over time. Previously, we designed a next-generation synthetic humanized...
ABSTRACT Rift Valley fever virus (RVFV) is an arbovirus within the Bunyaviridae family capable of causing serious morbidity and mortality in humans livestock. To identify host factors involved bunyavirus replication, we employed genome-wide RNA interference (RNAi) screening identified 381 genes whose knockdown reduced infection. The Wnt pathway was most represented when gene hits were functionally clustered. With further investigation, found that RVFV infection activated signaling, enhanced...
A rapid response is necessary to contain emergent biological outbreaks before they can become pandemics. The novel coronavirus (SARS-CoV-2) that causes COVID-19 was first reported in December of 2019 Wuhan, China and reached most corners the globe less than two months. In just over a year since initial infections, infected almost 100 million people worldwide. Although similar SARS-CoV MERS-CoV, SARS-CoV-2 has resisted treatments are effective against other coronaviruses. Crystal structures...
While the IMRAD (Introduction, Methods, Results, and Discussion) format is common in scientific writing, it may not currently be as ubiquitous often thought. We undertook a systematic, corpus-based study of primary section headings research articles across range STEM disciplines to investigate adherence structure relation type (computational, empirical, or theoretical) field. identified four categories structure: IMRAD, IMRAD+ (IMRAD with additional sections and/or different order), Nested...
Combined activity- and immunoassays for CRISPR/Cas9 on a portable microfluidic device with integrated sample preparation from clinical matrices.
The respiratory virus responsible for coronavirus disease 2019 (COVID-19), severe acute syndrome 2 (SARS-CoV-2), has affected nearly every aspect of life worldwide, claiming the lives over 3.9 million people globally, at time this publication. Neutralizing humanized nanobody (VHH)-based antibodies (VHH-huFc) represent a promising therapeutic intervention strategy to address current SARS-CoV-2 pandemic and provide powerful toolkit future outbreaks. Using synthetic, high-diversity VHH...
The high-affinity receptor for IgE expressed on the surface of mast cells and basophils interacts with antigens, via bound antibody, triggers secretion inflammatory mediators that contribute to allergic reactions. To understand how past inputs (memory) influence future responses in cells, a microfluidic device was used precisely control exposure alternating stimulatory non-stimulatory inputs. We determined response subsequent stimulation depends interval signaling quiescence. For shorter...
The RNA-guided DNA nuclease Cas9 is now widely used for the targeted modification of genomes human cells and various organisms. Despite extensive use Clustered Regularly Interspaced Palindromic Repeats (CRISPR) systems genome engineering rapid discovery new CRISPR-associated nucleases, there are no high-throughput assays measuring enzymatic activity. current laboratory future therapeutic uses CRISPR technology have a significant risk accidental exposure or clinical off-target effects,...
RNA interference (RNAi) is a powerful tool for functional genomics with the capacity to comprehensively analyze host–pathogen interactions. High-throughput RNAi screening used systematically perturb cellular pathways and discover therapeutic targets, but method can be tedious requires extensive capital equipment expensive reagents. To aid in development of an inexpensive miniaturized platform, we have developed two part microfluidic system patterning gene targets on-chip examine involved...
Structure-based Deep Fusion models were recently shown to outperform several physics- and machine learning-based protein-ligand binding affinity prediction methods. As part of a multi-institutional COVID-19 pandemic response, over 500 million small molecules computationally screened against four protein structures from the novel coronavirus (SARS-CoV-2), which causes COVID-19. Three enhancements made in order evaluate more than 5 billion docked poses on SARS-CoV-2 targets. First, concept was...
ABSTRACT Engineered monoclonal antibodies (mAbs) have proven to be highly effective therapeutics in recent viral outbreaks due their specificity and ability provide immediate protection, regardless of immune status. However, despite technical advancements the field, an rapidly adapt or increase antibody affinity by extension, therapeutic efficacy, has yet fully realized. We endeavored stand-up such a pipeline using molecular modeling combined with experimental library screening given...
Structure-based Deep Fusion models were recently shown to outperform several physics- and machine learning-based protein-ligand binding affinity prediction methods. As part of a multi-institutional COVID-19 pandemic response, over 500 million small molecules computationally screened against four protein structures from the novel coronavirus (SARS-CoV-2), which causes COVID-19. Three enhancements made in order evaluate more than 5 billion docked poses on SARS-CoV-2 targets. First, concept was...