A5023982770- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- Animal Virus Infections Studies
- Nuclear Structure and Function
- RNA Research and Splicing
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Poxvirus research and outbreaks
- Viral gastroenteritis research and epidemiology
- RNA regulation and disease
- Immunotherapy and Immune Responses
- Genetic Neurodegenerative Diseases
- Cellular transport and secretion
- Neurological disorders and treatments
- Long-Term Effects of COVID-19
- Herpesvirus Infections and Treatments
- Microtubule and mitosis dynamics
- DNA Repair Mechanisms
- COVID-19 epidemiological studies
- Viral Infections and Outbreaks Research
- T-cell and B-cell Immunology
- vaccines and immunoinformatics approaches
- Endoplasmic Reticulum Stress and Disease
3M (United States)
2023
Albert Einstein College of Medicine
2020-2023
Yale University
2015-2020
Institute of Molecular Biology and Biophysics
2019
Seeking broad protection As scientists develop therapeutic antibodies and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the risk of emergent coronaviruses makes it important to also identify broadly protective antibodies. Wec et al. isolated characterized hundreds viral spike protein SARS-CoV-2 from memory B cells a survivor 2003 outbreak caused by related coronavirus, SARS-CoV. In both these viruses, facilitated entry binding angiotensin-converting enzyme...
Coronavirus disease 2019 (COVID-19) is a global health crisis caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and there critical need to produce large quantities of high-quality SARS-CoV-2 Spike (S) protein for use in both clinical basic science settings. To address this need, we have evaluated expression purification two previously reported S constructs Expi293F ExpiCHO-S cells, different cell lines selected increased expression. We show that cells enhanced...
The human genome encodes four Torsin ATPases, the functions of which are poorly understood. In this study, we use CRISPR/Cas9 engineering to delete all ATPases individually and in combination. Using nuclear envelope (NE) blebbing as a phenotypic measure, establish direct correlation between number inactivated alleles occurrence omega-shaped herniations within lumen NE. A similar, although not identical, redundancy is observed for LAP1 LULL1, serve regulatory cofactors subset ATPases....
Nuclear envelope herniations (blebs) containing FG-nucleoporins and ubiquitin are the phenotypic hallmark of Torsin ATPase manipulation. Both dynamics blebbing connection to nuclear pore biogenesis remain poorly understood. We employ a proteomics-based approach identify myeloid leukemia factor 2 (MLF2) as luminal component bleb. Using an MLF2-based live-cell imaging platform, we demonstrate that occurs rapidly synchronously immediately after reformation during mitosis. Bleb formation is...
The U.S. FDA has issued emergency use authorizations (EUAs) for multiple investigational monoclonal antibody (MAb) therapies the treatment of mild to moderate COVID-19.
Convalescent plasma with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) antibodies (CCP) may hold promise as a treatment for 2019 (COVID-19). We compared the mortality and clinical outcome of patients COVID-19 who received 200 mL CCP spike protein IgG titer ≥ 1:2430 (median 1:47,385) within 72 hours admission propensity score-matched controls cared at medical center in Bronx, between April 13 May 4, 2020. Matching criteria were age, sex, body mass index, race, ethnicity,...
ABSTRACT TorsinA is a membrane-tethered AAA+ ATPase implicated in nuclear envelope dynamics as well the egress of herpes simplex virus 1 (HSV-1). The activity and related TorsinB strictly depends on LAP1 LULL1, type II transmembrane proteins that are integral parts Torsin/cofactor AAA ring, forming composite, membrane-spanning assembly. Here, we use CRISPR/Cas9-mediated genome engineering to create single- double knockout (KO) cell lines TorA TorB their activators, investigate effect HSV-1...
Broadly protective vaccines against known and pre-emergent coronaviruses are urgently needed. Critical to their development is a deeper understanding of cross-neutralizing antibody responses induced by natural human coronavirus (HCoV) infections. Here, we mined the memory B cell repertoire convalescent SARS donor identified 200 SARS-CoV-2 binding antibodies that target multiple conserved sites on spike (S) protein. A large proportion display high levels somatic hypermutation cross-react with...
TorsinA is an essential AAA+ ATPase requiring LAP1 or LULL1 as cofactors. The dynamics of the Torsin/cofactor system remain poorly understood, with previous models invoking assemblies fixed stoichiometries. Here we demonstrate that assembles into homotypic oligomers in presence ATP. Torsin variants mutated at "back" interface disrupt homo-oligomerization but still show robust activity its These mutants are severely compromised their ability to rescue nuclear envelope defects Torsin-deficient...
ABSTRACT Coronavirus disease 2019 ( COVID-19 ) is a global health crisis caused by the novel severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 ), and there critical need to produce large quantities of high-quality Spike S protein for use in both clinical basic science settings. To address this need, we have evaluated expression purification two previously reported constructs Expi293F ™ ExpiCHO-S cells, different cell lines selected increased secreted glycoproteins. We show that...
The clinical outcome of SARS-CoV-2 infection varies widely between individuals. Machine learning models can support decision making in healthcare by assessing fatality risk patients that do not yet show severe signs COVID-19. Most predictive rely on static demographic features and values obtained upon hospitalization. However, time-dependent biomarkers associated with COVID-19 severity, such as antibody titers, substantially contribute to the development more accurate models. Here we trained...
Summary There is an urgent need for vaccines and therapeutics to prevent treat COVID-19. Rapid SARS-CoV-2 countermeasure development contingent on the availability of robust, scalable, readily deployable surrogate viral assays screen antiviral humoral responses, define correlates immune protection, down-select candidate antivirals. Here, we describe a highly infectious recombinant vesicular stomatitis virus bearing spike glycoprotein S as its sole entry that closely resembles authentic agent...
Torsins are essential, disease-relevant AAA+ (ATPases associated with various cellular activities) proteins residing in the endoplasmic reticulum and perinuclear space, where they implicated a variety of functions. Recently, new structural functional details about have emerged that will profound influence on unraveling precise mechanistic their yet-unknown mode action cell. While phylogenetically related to Clp/HSP100 proteins, exhibit comparatively weak ATPase activities, which tightly...
The coronavirus disease 2019 (COVID-19) global pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2) continues to place an immense burden on societies and health care systems. A key component of COVID-19 control efforts is serological testing determine the community prevalence SARS-CoV-2 exposure quantify individual immune responses prior infection or vaccination. Here, we describe a laboratory-developed antibody test that uses readily available research-grade reagents detect...
Abstract Convalescent plasma with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) antibodies (CCP) may hold promise as treatment for Coronavirus Disease 2019 (COVID-19). We compared the mortality and clinical outcome of patients COVID-19 who received 200mL CCP a Spike protein IgG titer ≥1:2,430 (median 1:47,385) within 72 hours admission to propensity score-matched controls cared at medical center in Bronx, between April 13 May 4, 2020. Matching criteria were age, sex, body mass...
Abstract Both infection and autoimmune disease can disrupt pre-existing Ab titers leading to diminished serological memory, yet the underlying mechanisms are not well understood. In this article, we report that TNF-α, an inflammatory cytokine, is a master regulator of plasma cell (PC) niche in bone marrow (BM). Acute rTNF-α treatment depletes previously existing after vaccination by limiting PC occupancy or retention BM. Consistent with phenomenon, mice lacking TNF-α signaling have elevated...
The COVID-19 global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to place an immense burden on societies and healthcare systems. A key component of control efforts is serologic testing determine the community prevalence SARS-CoV-2 exposure quantify individual immune responses prior infection or vaccination. Here, we describe a laboratory-developed antibody test that uses readily available research-grade reagents detect in patient blood samples...
The Bronx was an early epicenter of the COVID-19 pandemic in United States. We conducted temporal genomic surveillance 104 SARS-CoV-2 genomes across from March to October 2020. Although local structure lineages mirrored those New York City and State, sampling revealed a dynamic changing landscape diversity. Mapping trajectories mutations, we found that although some became “endemic” Bronx, other, novel mutations rose prevalence late summer/early fall. Geographically resolved enabled us...
Abstract Nuclear envelope herniations (blebs) containing FG-nucleoporins and ubiquitin are the phenotypic hallmark of Torsin ATPase manipulation. Both dynamics blebbing connection to nuclear pore biogenesis remain poorly understood. We employ a proteomics-based approach identify MLF2 as luminal component bleb. Using an MLF2-based live cell imaging platform, we demonstrate that NE occurs rapidly synchronously immediately after reformation during mitosis. Bleb formation is independent...
Abstract Most known SARS-CoV-2 neutralizing antibodies (nAbs), including those approved by the FDA for emergency use, inhibit viral infection targeting receptor-binding domain (RBD) of spike (S) protein. Variants concern (VOC) carrying mutations in RBD or other regions S reduce effectiveness many nAbs and vaccines evading neutralization. Therefore, therapies that are less susceptible to resistance urgently needed. Here, we characterized memory B-cell repertoire COVID-19 convalescent donors...
TorsinA is an essential AAA+ ATPase requiring LAP1 or LULL1 as cofactors. The dynamics of the Torsin/cofactor system remain poorly understood, with previous models invoking assemblies fixed stoichiometries. Here we demonstrate that assembles into homotypic oligomers in presence ATP. Torsin variants mutated at “back” interface disrupt homo‐oligomerization but still show robust activity its These mutants are severely compromised their ability to rescue nuclear envelope defects Torsin‐deficient...