A5064286710- Lysosomal Storage Disorders Research
- Cellular transport and secretion
- SARS-CoV-2 and COVID-19 Research
- Mosquito-borne diseases and control
- Calcium signaling and nucleotide metabolism
- Sphingolipid Metabolism and Signaling
- Animal Virus Infections Studies
- HIV Research and Treatment
- COVID-19 Clinical Research Studies
- Bacillus and Francisella bacterial research
- Immunotherapy and Immune Responses
- Viral gastroenteritis research and epidemiology
- COVID-19 and healthcare impacts
- Carbohydrate Chemistry and Synthesis
- Yersinia bacterium, plague, ectoparasites research
- Respiratory viral infections research
- Influenza Virus Research Studies
- Retinal Development and Disorders
- Lipid Membrane Structure and Behavior
- Complement system in diseases
- Immune Cell Function and Interaction
- Neuroinflammation and Neurodegeneration Mechanisms
- CAR-T cell therapy research
- SARS-CoV-2 detection and testing
- Trypanosoma species research and implications
Harvard University
2024
Israel Institute for Biological Research
2018-2023
Institute for Biological Sciences
2021
Weizmann Institute of Science
2009-2016
Weatherford College
2014
Abstract The COVID-19 pandemic caused by SARS-CoV-2 imposes an urgent need for rapid development of efficient and cost-effective vaccine, suitable mass immunization. Here, we show the a replication competent recombinant VSV-∆G-spike in which glycoprotein VSV is replaced spike protein SARS-CoV-2. In-vitro characterization this vaccine indicates expression presentation on viral membrane with antigenic similarity to A golden Syrian hamster in-vivo model implemented. We that single-dose...
Gaucher's disease, the most common lysosomal storage disorder, is caused by defective activity of glucocerebrosidase, hydrolase that degrades glucosylceramide. The neuronopathic forms disease are characterized severe neuronal loss, astrocytosis and microglial proliferation, but cellular molecular pathways causing these changes not known. In current study, we delineate role neuroinflammation in pathogenesis show significant levels inflammatory mediators brain a mouse model. Levels messenger...
Gaucher disease has recently received wide attention due to the unexpected discovery that it is a genetic risk factor for Parkinson's disease. caused by defective activity of lysosomal enzyme, glucocerebrosidase (GCase; GBA1), resulting in intracellular accumulation glycosphingolipids, glucosylceramide and psychosine. The rare neuronopathic forms GD (nGD) are characterized profound neurological impairment neuronal cell death. We have previously described progression neuropathological changes...
Environmental surfaces have been suggested as likely contributors in the transmission of COVID-19. This study assessed infectivity severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contaminating and objects two hospital isolation units a quarantine hotel.
Abstract The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome 2 (SARS-CoV-2), exhibits high levels of mortality and morbidity has dramatic consequences on human life, sociality global economy. Neutralizing antibodies constitute a highly promising approach for treating preventing infection this novel pathogen. In present study, we characterize further evaluate recently identified monoclonal MD65 antibody its ability to provide protection against...
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of ongoing disease 2019 (COVID-19) pandemic. The continued spread SARS-CoV-2 increases probability influenza/SARS-CoV-2 coinfection, which may result in severe disease. In this study, we examine outcome influenza A virus (IAV) and coinfection K18-hACE2 mice. Our data indicate enhance susceptibility IAV-infected mice to developing upon with two days later. contrast nonfatal lower mortality rates due alone,...
Gaucher disease (GD), the most common lysosomal storage disorder, is caused by a deficiency in enzyme glucocerebrosidase (GlcCerase), which results intracellular accumulation of glucosylceramide (GlcCer). The rare neuronopathic forms GD are characterized profound neurological impairment and neuronal cell death, but little known about neuropathological changes that underlie these events. We now systematically examine onset progression various (including microglial activation, astrogliosis...
Neuroinflammation is a key phenomenon in the pathogenesis of many neurodegenerative diseases. Understanding mechanisms by which brain inflammation engaged and delineating players immune response their contribution to pathology great importance for identification novel therapeutic targets these devastating Gaucher disease, most common lysosomal storage caused mutations GBA1 gene significant risk factor Parkinson's disease; some forms neuroinflammation observed.An unbiased profile analysis was...
The neuronopathic forms of the human inherited metabolic disorder, Gaucher disease (GD), are characterized by severe neuronal loss, astrogliosis and microglial proliferation, but cellular molecular pathways causing these changes not known. Recently, a mouse model GD was generated in which glucocerebrosidase deficiency is limited to neural glial progenitor cells. We now show significant levels distribution cathepsins brain this model. Cathepsin mRNA expression significantly elevated up...
Great interest has been shown in understanding the pathology of Gaucher disease (GD) due to recently discovered genetic relationship with Parkinson's disease. For such studies, suitable animal models GD are required. Chemical induction by inhibition acid β-glucosidase (GCase) using irreversible inhibitor conduritol B-epoxide (CBE) is particularly attractive, although few systematic studies examining effect CBE on development symptoms associated neurological forms have performed. We now...
The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major threat to global health. Vaccines are ideal solutions prevent infection, but treatments also needed for those who have contracted the virus limit negative outcomes, when vaccines not applicable. Viruses must cross host cell membranes during their life cycle, creating dependency on processes involving membrane dynamics. Thus, in this study, we examined whether synthetic machinery...
Understanding pathways that might impact coronavirus disease 2019 (COVID-19) manifestations and outcomes is necessary for better management therapeutic development. Here, we analyzed alterations in sphingolipid (SL) levels upon infection with severe acute respiratory syndrome 2 (SARS-CoV-2). SARS-CoV-2 induced elevation of SL both cells sera infected mice. A significant increase glycosphingolipid was early post infection, which essential viral replication. This could be reversed by treatment...
Although coronavirus disease 2019 (COVID-19) causes significan t morbidity, mainly from pulmonary involvement, extrapulmonary symptoms are also major componen ts of the disease. Kidney disease, usually presenting as AKI, is particularly severe among patients with COVID-19. It unknown, however, whether such injury results direct kidney infection COVID-19's causative virus, acute respiratory syndrome 2 (SARS-CoV-2), or indirect mechanisms.
Artificial antigen-presenting cells (aAPCs) are currently used to manufacture T for adoptive therapy in cancer treatment, but a readily tunable and modular system can enable both rapid cell expansion control over phenotype. Here, it is shown that microgels with tailored surface biochemical properties serve as aAPCs mediate activation expansion. Surface functionalization of achieved via layer-by-layer coating using oppositely charged polymers, forming thin dense polymer layer on the surface....
Gaucher disease (GD), the most common lysosomal storage disorder (LSD), is caused by defects in activity of enzyme, glucocerebrosidase, resulting intracellular accumulation glucosylceramide (GlcCer). Neuronopathic forms, which comprise only a small percent GD patients, are characterized neurological impairment and neuronal cell death. Little known about pathways leading from GlcCer to death or dysfunction but defective calcium homeostasis appears be one involved. Recently, endoplasmic...
Abstract The COVID-19 pandemic caused by SARS-CoV-2 that emerged in December 2019 China resulted over 7.8 million infections and 430,000 deaths worldwide, imposing an urgent need for rapid development of efficient cost-effective vaccine, suitable mass immunization. Here, we generated a replication competent recombinant VSV-ΔG-spike which the glycoprotein VSV was replaced spike protein SARS-CoV-2. In vitro characterization indicated expression presentation on viral membrane with antigenic...
Abstract Most lysosomal storage diseases (LSDs) have a significant neurological component, including types 2 and 3 Gaucher disease (neuronal forms of disease; nGD). No therapies are currently available for nGD since the recombinant enzymes used in systemic form do not cross blood–brain barrier (BBB). However, number promising approaches being tested, substrate reduction therapy (SRT), which partial inhibition synthesis glycosphingolipids (GSLs) that accumulate lowers their accumulation. We...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Currently, as dangerous mutations emerge, there an increased demand specific treatments SARS-CoV-2 infected patients. The spike glycoprotein on virus envelope binds to angiotensin converting enzyme (ACE2) host cells through its receptor binding domain (RBD) mediate entry. Thus, blocking this interaction may inhibit viral entry and consequently stop infection. Here, we generated fusion...
Abstract Virus-induced CNS diseases impose a considerable human health burden worldwide. For many viral infections, neither antiviral drugs nor vaccines are available. In this study, we examined whether the synthesis of glycosphingolipids, major membrane lipid constituents, could be used to establish an therapeutic target. We found that neuroinvasive Sindbis virus altered sphingolipid levels early after infection in vitro and increased gangliosides GA1 GM1 sera infected mice. The alteration...