- Viral Infections and Vectors
- Viral Infections and Outbreaks Research
- Neuroscience and Neuropharmacology Research
- Memory and Neural Mechanisms
- Tuberculosis Research and Epidemiology
- Neural dynamics and brain function
- Cutaneous Melanoma Detection and Management
- Protein Kinase Regulation and GTPase Signaling
- Sleep and Wakefulness Research
- Viral gastroenteritis research and epidemiology
- Phytase and its Applications
- Retinopathy of Prematurity Studies
- Lysosomal Storage Disorders Research
- Biliary and Gastrointestinal Fistulas
- Retinal Development and Disorders
- Immune Cell Function and Interaction
- Cellular transport and secretion
- Estrogen and related hormone effects
- Mosquito-borne diseases and control
- Hepatitis B Virus Studies
- Pneumocystis jirovecii pneumonia detection and treatment
- EEG and Brain-Computer Interfaces
- Alzheimer's disease research and treatments
- Liver Disease Diagnosis and Treatment
- Cancer therapeutics and mechanisms
Montefiore Einstein Comprehensive Cancer Center
2024
Albert Einstein College of Medicine
2021-2024
Montefiore Medical Center
2024
Kaiser Permanente San Francisco Medical Center
2023-2024
Jacobs (United States)
2021
Icahn School of Medicine at Mount Sinai
1989-2015
Queen's University
2011-2015
New York Proton Center
2015
Edendale Hospital
2009
Monash University
2005
Ebola virus (EBOV) infection blocks cellular production of alpha/beta interferon (IFN-alpha/beta) and the ability cells to respond IFN-alpha/beta or IFN-gamma. The EBOV VP35 protein has previously been identified as an EBOV-encoded inhibitor production. However, mechanism by which inhibits responses IFNs not defined. Here we demonstrate that VP24 functions IFN-gamma signaling. Expression results in inhibition IFN-induced gene expression inability induce antiviral state. VP24-mediated...
Severe influenza disease strikes otherwise healthy children and remains unexplained. We report compound heterozygous null mutations in IRF7, which encodes the transcription factor interferon regulatory 7, an child who suffered life-threatening during primary infection. In response to virus, patient's leukocytes plasmacytoid dendritic cells produced very little type I III interferons (IFNs). Moreover, dermal fibroblasts induced pluripotent stem cell (iPSC)-derived pulmonary epithelial reduced...
Significance Tuberculosis (TB) patients would greatly benefit from shorter treatment options. The of drug-susceptible TB, a disease caused by the bacillus Mycobacterium tuberculosis , is lengthy and strenuous process. This long therapy because ability small population cells to become drug-tolerant. Here, we demonstrate that addition thiols drug-treated M. prevents emergence drug-tolerant but also drug-resistant leading sterilization cultures in vitro. potentiate drug activity preventing...
Daily phagocytosis of spent photoreceptor outer segments is a critical maintenance function performed by the retinal pigment epithelium (RPE) to preserve vision. Aging RPE accumulates lipofuscin, which includes N -retinylidene- -retinylethanolamine (A2E) as major autofluorescent component. We studied effect physiological levels A2E in cultures on their ability phagocytose segments. localized lysosomes cultured well human situ . A2E-loaded cells culture bound and internalized identical...
The Ebolavirus VP24 protein counteracts alpha/beta interferon (IFN-alpha/beta) and IFN-gamma signaling by blocking the nuclear accumulation of tyrosine-phosphorylated STAT1 (PY-STAT1). According to proposed model, binding members NPI-1 subfamily karyopherin alpha (KPNalpha) localization signal receptors prevents their PY-STAT1, thereby preventing PY-STAT1 accumulation. This study now identifies two domains required for inhibition IFN-beta-induced gene expression We demonstrate that loss...
Estrogen reduces the risk of Alzheimer's disease in post-menopausal women, β-amyloid (Aβ) burden animal models disease, and secretion Aβ from neuronal cultures. The biological basis for these effects remains unknown. Here, utilizing cell-free systems derived both neuroblastoma cells primary neurons, we demonstrate that 17β-estradiol (17β-E2) stimulates formation vesicles containing precursor protein (βAPP) trans-Golgi network (TGN). Accelerated βAPP trafficking precludes maximal generation...
CA1 pyramidal cell is modeled by a linked series of passive compartments representing the soma and different parts dendritic tree. Intracellular postsynaptic potentials are simulated conductance changes at one or more compartments. By assuming an infinite homogeneous extracellular medium particular geometrical arrangement cells, field potential profiles generated from current source-sinks The cells driven theta (theta)-frequency sites tree in order to simulate external driving hippocampus...
Significance Tuberculosis drug development remains crucial for countering the spread of resistance worldwide. New susceptibilities in metabolic pathways must be identified to find novel drugs eradicate tuberculosis. The electron transport chain (ETC) is target recently developed tuberculosis drugs. To assess whether NADH dehydrogenases ETC would potential candidates, we deleted genes encoding three Mycobacterium Nuo, Ndh, and NdhA. We found that although were not essential growth...
ABSTRACT Drug resistance in Mycobacterium tuberculosis has become a serious global health threat, which is now complicated by the emergence of extensively drug-resistant strains. New drugs that are active against (TB) needed. We chose to search for new inhibitors enoyl-acyl carrier protein (ACP) reductase InhA, target first-line TB drug isoniazid (also known as isonicotinoic acid hydrazide [INH]). A subset chemical library, composed 300 compounds inhibiting Plasmodium falciparum enoyl...
Ebolaviruses naturally infect a wide variety of cells including macrophages and dendritic (DCs), the resulting cytokine interferon‐α/β (IFN) responses infected are thought to influence viral pathogenesis. The VP35 protein impairs RIG‐I‐like receptor‐dependent signaling inhibit IFN production, this function has been suggested promote ineffective host immune response characteristic ebolavirus infection. To assess impact on innate immunity in biologically relevant primary cells, we used...
The Zaire Ebola virus (EBOV) protein VP35 is multifunctional; it inhibits IFN-α/β production and functions as a cofactor of the viral RNA polymerase. Mass spectrometry identified double stranded binding 76 (DRBP76/NFAR-1/NF90) cellular factor that associates with C-terminal interferon inhibitory domain (IID). DRBP76 described to regulate host cell synthesis play an important role in defense. VP35-IID-DRBP76 interaction required addition exogenous dsRNA, but full-length associated absence...
Zaire Ebola virus (EBOV) is a zoonotic pathogen that causes severe hemorrhagic fever in humans. A single viral glycoprotein (GP) mediates attachment and entry. Here, virus-like particle (VLP)-based entry assays demonstrate GP mutant, GP-F88A, which defective for into variety of human cell types, including antigen-presenting cells (APCs), such as macrophages dendritic cells, can mediate mouse CD11b(+) APCs. Like wild-type (GP-wt), GP-F88A-mediated occurs via macropinocytosis-related pathway...
Eastern equine encephalitis virus (EEEV) is a human and veterinary pathogen that causes sporadic cases of fatal neurological disease. We previously demonstrated the capsid protein EEEV potent inhibitor host cell gene expression this function maps to amino terminus protein. now identify acids 55 75, within N capsid, as critical for inhibition expression. An analysis stable replicons expressing mutant proteins corroborated these mapping data. When deletions 5 20 region were introduced into...
1. The field potentials and unit activities evoked by the alvear tract (AT) in CA1 region of dorsal hippocampus rats were studied under sodium pentobarbital anesthesia. 2. localized activity anterior to an AT stimulus began as a compound action potential, followed slower negative wave, ended long-lasting, slow positive wave. Observed with 64-electrode recording array, topographical projections seen parallel strips inclined at angle 5-30 degrees medially from sagittal plane. 3. Three...
We prepared a nanopatterned polymer film of polydimethylsiloxane (PDMS)<italic>via</italic>virus imprinting.
We examined the ability of Ebola virus to elicit an antiviral response from plasmacytoid dendritic cells (pDCs). Exposure pDCs did not result in significantly higher levels interferon-α production than mock-infected cells. After inoculation with under same conditions, conventional expressed viral proteins whereas not, suggesting that latter were infected. Assessment entry virus-like particles into revealed are highly impaired for comparison These observations identify a novel means by which...
Significance Despite decades of research, we lack an effective vaccine against influenza, a deadly virus that costs the United States nearly $90 billion annually. Current strategies do not translate into highly protective immunity circulating and novel influenza strains. Here, demonstrate herpes simplex viral (HSV) vector expressing hemagglutinin can be used to elicit response influenza. The efficacy this is abrogated by preexisting HSV, protects lethal HSV challenge, elicits functional...