A5008849295- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- Animal Virus Infections Studies
- Immunotherapy and Immune Responses
- HIV Research and Treatment
- Glycosylation and Glycoproteins Research
- Viral Infections and Immunology Research
- Nuclear Structure and Function
- Cancer, Hypoxia, and Metabolism
- COVID-19 Clinical Research Studies
- CAR-T cell therapy research
- Viral gastroenteritis research and epidemiology
- Immune Cell Function and Interaction
- RNA Research and Splicing
- Microtubule and mitosis dynamics
- T-cell and B-cell Immunology
- SARS-CoV-2 detection and testing
- Estrogen and related hormone effects
- Virology and Viral Diseases
- Influenza Virus Research Studies
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- RNA regulation and disease
- Enzyme Structure and Function
- Advanced biosensing and bioanalysis techniques
California Institute of Technology
2018-2024
Integrated BioTherapeutics (United States)
2024
Harvard University
2017
Boston Children's Hospital
2017
The coronavirus disease 2019 (COVID-19) pandemic presents an urgent health crisis. Human neutralizing antibodies that target the host ACE2 receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein
Identification of maturation stages V3-glycan neutralizing antibodies explains the long duration required for their development.
To combat future severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles that present randomly arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against epitopes are conserved relatively occluded rather than variable, immunodominant, exposed. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 seven animal...
INTRODUCTION The subcellular compartmentalization of eukaryotic cells requires selective transport folded proteins and protein-nucleic acid complexes. Embedded in nuclear envelope pores, which are generated by the circumscribed fusion inner outer membranes, pore complexes (NPCs) sole bidirectional gateways for nucleocytoplasmic transport. ~110-MDa human NPC is an ~1000-protein assembly that comprises multiple copies ~34 different proteins, collectively termed nucleoporins. symmetric core...
The nuclear pore complex (NPC) controls the passage of macromolecules between nucleus and cytoplasm, but how NPC directly participates in macromolecular transport remains poorly understood. In final step mRNA export, DEAD-box helicase DDX19 is activated by nucleoporins Gle1, Nup214, Nup42 to remove Nxf1•Nxt1 from mRNAs. Here, we report crystal structures Gle1•Nup42 three organisms that reveal an evolutionarily conserved binding mode. Biochemical reconstitution ATPase cycle establishes human...
Abstract The COVID-19 pandemic presents an urgent health crisis. Human neutralizing antibodies (hNAbs) that target the host ACE2 receptor-binding domain (RBD) of SARS-CoV-2 spike 1–5 show therapeutic promise and are being evaluated clincally 6–8 . To determine structural correlates neutralization, we solved 8 new structures distinct hNAbs 5 in complex with trimer or RBD. Structural comparisons allowed classification into categories: (1) VH3-53 short CDRH3s block bind only to “up” RBDs, (2)...
Abstract Human immunodeficiency virus-1 (HIV-1), the causative agent of AIDS, impacts millions people. Entry into target cells is mediated by HIV-1 envelope (Env) glycoprotein interacting with host receptor CD4, which triggers conformational changes allowing binding to a coreceptor and subsequent membrane fusion. Small molecule or peptide CD4-mimetic drugs mimic CD4’s Phe43 interaction Env inserting conserved pocket on subunit gp120. Here, we present single-particle cryo-EM structures...
Introduction Despite advances in treatment of blood cancers, several—including acute myeloid leukemia (AML)—continue to be recalcitrant. Cell therapies based on chimeric antigen receptors (CARs) have emerged as promising approaches for cancers. However, current CAR-T treatments suffer from on-target, off-tumor toxicity, because most familiar cancer targets are also expressed normal lineages. In addition, they face the common problem relapse due target-antigen loss. therapeutics engineered...
Clinical applications of CAR-T cells are limited by the scarcity tumor-specific targets and often afflicted with same on-target/off-tumor toxicities that plague other cancer treatments. A new promising strategy to enforce tumor selectivity is use logic-gated, two-receptor systems. One well-described application termed Tmod™, which originally utilized a blocking inhibitory receptor directed towards HLA-I target antigens create protective NOT gate. Here we show function Tmod blockers targeting...
Summary Many anti-SARS-CoV-2 neutralizing antibodies target the ACE2-binding site on viral spike receptor-binding domains (RBDs). The most potent recognize exposed variable epitopes, often rendering them ineffective against other sarbecoviruses and SARS-CoV-2 variants. Class 4 anti-RBD a less-exposed, but more-conserved, cryptic epitope could newly-emergent zoonotic variants, usually show only weak neutralization potencies. We characterized two class derived from COVID-19 donors that...
Abstract To combat future SARS-CoV-2 variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles presenting randomly-arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against conserved/relatively-occluded, rather than variable/immunodominant/exposed, epitopes. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 seven animal sarbecoviruses) homotypic (only SARS-CoV-2)...
Abstract Human Immunodeficiency Virus-1 (HIV-1), the causative agent of AIDS, impacts millions people. Entry into target cells is mediated by HIV-1 envelope (Env) glycoprotein interacting with host receptor CD4, which triggers conformational changes allowing binding to a coreceptor and subsequent membrane fusion. Small molecule or peptide CD4-mimetic drugs mimic CD4’s Phe43 interaction Env inserting conserved pocket on subunit gp120. Here, we present single-particle cryo-EM structures...