Michal Caspi Tal
- SARS-CoV-2 and COVID-19 Research
- Vector-borne infectious diseases
- Phagocytosis and Immune Regulation
- COVID-19 Clinical Research Studies
- interferon and immune responses
- Viral Infections and Vectors
- Respiratory viral infections research
- Insect and Pesticide Research
- Immunotherapy and Immune Responses
- Erythrocyte Function and Pathophysiology
- Heat shock proteins research
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- Dermatology and Skin Diseases
- T-cell and B-cell Immunology
- Complement system in diseases
- Inflammasome and immune disorders
- Mosquito-borne diseases and control
- SARS-CoV-2 detection and testing
- Immune responses and vaccinations
- Radiopharmaceutical Chemistry and Applications
- Cellular Mechanics and Interactions
- Vibrio bacteria research studies
- Toxin Mechanisms and Immunotoxins
- Autophagy in Disease and Therapy
Massachusetts Institute of Technology
2022-2024
Stanford University
2019-2024
Stanford Medicine
2022
California Institute for Regenerative Medicine
2020-2022
Institute for Stem Cell Biology and Regenerative Medicine
2022
Moscow Institute of Thermal Technology
2022
Stratford University
2020
Yale University
2009-2016
Tel Aviv University
2012
Autophagy is a highly conserved process that maintains homeostasis by clearing damaged organelles and long-lived proteins. The consequences of deficiency in autophagy manifest variety pathological states including neurodegenerative diseases, inflammatory disorders, cancer. Here, we studied the role homeostatic regulation innate antiviral defense. Single-stranded RNA viruses are recognized members RIG-I-like receptors (RLRs) cytosol. RLRs signal through IPS-1, resulting production key...
Although SARS-CoV-2 infects the upper respiratory tract, we know little about amount, type, and kinetics of antibodies (Ab) generated in oral cavity response to COVID-19 vaccination. We collected serum saliva samples from participants receiving two doses mRNA vaccines measured level anti-SARS-CoV-2 Ab. detected anti-Spike anti-Receptor Binding Domain (RBD) IgG IgA, as well anti-Spike/RBD associated secretory component most after dose 1. Administration a second boosted but not IgA response,...
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...
Our understanding of protective versus pathological immune responses to SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is limited by inadequate profiling patients at extremes severity spectrum. Here, we performed multi-omic single-cell 64 COVID-19 across full range severity, from outpatients with mild fatal cases. transcriptomic, epigenomic, and proteomic analyses revealed widespread dysfunction peripheral innate immunity in severe COVID-19, including prominent...
At this stage in the COVID-19 pandemic, most infections are "breakthrough" that occur individuals with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure. To refine long-term vaccine strategies against emerging variants, we examined both innate and adaptive immunity breakthrough infections. We performed single-cell transcriptomic, proteomic, functional profiling of primary to compare immune responses from unvaccinated vaccinated during SARS-CoV-2 Delta wave....
Significance This study demonstrates the efficacy of combining macrophage-checkpoint inhibition with tumor-specific antibodies for cancer immunotherapy. The combination anti-CD47 (magrolimab) and anti-HER2 (trastuzumab) eliminated HER2 + breast cells increased due to enhancement antibody-dependent cellular phagocytosis by macrophages, even when were tolerant trastuzumab-induced cytotoxicity natural killer cells. We believe these findings present a promising therapeutic approach treating...
Abstract Background The determinants of coronavirus disease 2019 (COVID-19) severity and extrapulmonary complications (EPCs) are poorly understood. We characterized relationships between severe acute respiratory syndrome 2 (SARS-CoV-2) RNAemia severity, clinical deterioration, specific EPCs. Methods used quantitative digital polymerase chain reaction (qPCR dPCR) to quantify SARS-CoV-2 RNA from plasma in 191 patients presenting the emergency department with COVID-19. recorded patient...
Abstract Lyme disease is a tick-borne caused by bacteria of the genus Borrelia . The host factors that modulate susceptibility for have remained mostly unknown. Using epidemiological and genetic data from FinnGen Estonian Biobank, we identify two previously known variants an unknown common missense variant at gene encoding Secretoglobin family 1D member 2 ( SCGB1D2 ) protein increases disease. live burgdorferi (Bb) find recombinant reference inhibits growth Bb in vitro more efficiently than...
Abstract Prolonged exposure of CD8 + T cells to antigenic stimulation, as in chronic viral infections, leads a state diminished function termed exhaustion. We now demonstrate that even during exhaustion there is subset functional defined by surface expression SIRPα, protein not previously reported on lymphocytes. On SIRPα cells, co-inhibitory receptors counterbalanced co-stimulatory and it only actively proliferate, transcribe IFNγ show cytolytic activity. Furthermore, target express the...
Paradoxically, early host responses to infection include the upregulation of antiphagocytic molecule, CD47. This suggests that CD47 blockade could enhance antigen presentation and subsequent immune responses. Indeed, mice treated with anti-CD47 monoclonal antibody following lymphocytic choriomeningitis virus infections show increased activation both macrophages dendritic cells (DCs), enhancement kinetics potency CD8+ T cell responses, significantly improved control. Treatment efficacy is...
It is well understood that the adaptive immune response to infectious agents includes a modulating suppressive component as an activating component. We now show very early innate also has immunosuppressive Infected cells upregulate CD47 "don't eat me" signal, which slows phagocytic uptake of dying and viable downstream antigen-presenting cell (APC) functions. A mimic acts essential virulence factor encoded by all poxviruses, but expression on infected was found be upregulated even pathogens,...
Borrelia burgdorferi (Bb), a vector-borne bacterial pathogen and the causative agent of Lyme disease, can spread to distant tissues in human host by traveling through monolayers endothelial cells (ECs) lining vasculature. To examine whether Bb alters physical forces ECs promote its dissemination, we exposed observed sharp transient increase EC traction intercellular forces, followed prolonged decrease motility forces. All variables returned baseline at 24 h after exposure. RNA sequencing...
Lyme disease (LD) is an illness caused by the spirochete Borrelia burgdorferi (B. burgdorferi). known to disseminate through organs, including skin, joints, spinal cord, bladder, and heart, leading arthritis, neuroborreliosis, carditis. While previous studies have investigated impact of LD on pregnancy in both mice humans found presence B. uterus mice, we studied non-pregnant female reproductive tract. We use a mouse model for find ongoing severe infection tract which persists up 15-months...
ABSTRACT Vaccination induced antibody and T-cell immune responses are important for systemic protection from COVID-19. Because SARS-CoV-2 infects is transmitted by oral-pharyngeal mucosa, we wished to test mucosal antibodies elicited natural infection or intramuscular vaccine injection. In a non-randomized observational study, measured against the RBD in plasma saliva convalescent vaccinated individuals tested their neutralizing potential using replication competent rVSV-eGFP-SARS-CoV-2. We...
Innate immunity to viral infection is initiated within the infected cells through recognition of unique signatures by pattern receptors (PRRs) that mediate induction potent antiviral factor, type I interferons (IFNs). Infection with RNA viruses recognized members retinoic acid inducible gene (RIG-I)-like receptor (RLR) family in cytosol. Our recent study demonstrates IFN production response ligands increased absence autophagy. The process autophagy functions as an internal cleanup crew cell,...
Significance Novel therapies are urgently needed that can ameliorate the clinical syndromes of cerebral malaria, most severe consequences Plasmodium infection, and thereby reduce malaria fatality. Monoclonal antibodies target CD47, a “don’t eat me” signal, have been demonstrated to enhance cellular clearance cancer cells by promoting macrophage phagocytosis. We sought adopt this therapeutic strategy associated with goals reducing disease-associated morbidity mortality. demonstrate CD47...
Abstract Although SARS-CoV-2 infects the upper respiratory tract, we know little about amount, type, and kinetics of antibodies (Ab) generated at this site in response to intramuscular COVID-19 vaccination, whether these Ab protect against subsequent “breakthrough” infections. We collected longitudinal serum saliva samples from participants receiving two doses mRNA vaccines over a 6-month period measured relative level anti-Spike anti-Receptor Binding Domain (RBD) Ab. detected anti-Spike/RBD...
Clinicians in the emergency department (ED) face challenges concurrently assessing patients with suspected COVID-19 infection, detecting bacterial coinfection, and determining illness severity since current practices require separate workflows. Here, we explore accuracy of IMX-BVN-3/IMX-SEV-3 29 mRNA host response classifiers simultaneously severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection coinfections predicting clinical COVID-19. A total 161 PCR-confirmed (52.2%...
Many patients experience persistent symptoms after COVID-19, a syndrome referred to as Long COVID (LC). The goal of this study was identify novel new or worsening comorbidities self-reported in with LC.