A5061593814- Genetics and Neurodevelopmental Disorders
- Nicotinic Acetylcholine Receptors Study
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Ubiquitin and proteasome pathways
- Cholinesterase and Neurodegenerative Diseases
- Epigenetics and DNA Methylation
- Protein Degradation and Inhibitors
- Memory and Neural Mechanisms
- Congenital heart defects research
- Alzheimer's disease research and treatments
- Neurobiology and Insect Physiology Research
- Autism Spectrum Disorder Research
- Neuroscience and Neuropharmacology Research
- Drug Transport and Resistance Mechanisms
- Mycobacterium research and diagnosis
- Allergic Rhinitis and Sensitization
- RNA Research and Splicing
- RNA modifications and cancer
- HIV Research and Treatment
- Animal Behavior and Reproduction
- Reproductive System and Pregnancy
- Antioxidant Activity and Oxidative Stress
- Neuroinflammation and Neurodegeneration Mechanisms
- Pneumocystis jirovecii pneumonia detection and treatment
Broad Institute
2022-2024
University of Pennsylvania
2000-2016
Albert Einstein College of Medicine
2009-2016
Drexel University
2004-2016
Yeshiva University
2016
Valley Health System
2010-2015
Lehigh Valley Hospital-Pocono
2010-2013
Lehigh Valley Health Network
2009
McGill University
2008
Institute for Molecular Medicine
2004
Two functional types of nicotinic acetylcholine receptors (nAChRs) are expressed when human embryonic kidney cells permanently transfected with equal amounts alpha4 and beta2 subunit cDNAs. Most (82%) these nAChRs exhibit an EC(50) 74 +/- 6 microM for ACh, a much lower sensitivity than the remaining fraction (EC(50) 0.7 0.4 microM) or expected from expression mRNAs in Xenopus laevis oocytes. We have found three conditions that can increase number high to activation. These are: 1) transient...
Atopic dermatitis (AD) is thought to be a double-hit phenomenon with an unknown environmental component and genetic abnormality likely centered on the filaggrin gene. Biologically, presence of Staphylococcus aureus in AD was reported more than 2 decades ago, but relationship has been elusive.To explore bacteria that produce biofilms lesions response innate immune system these biofilm occlusions sweat ducts by specifically evaluating Toll-like receptor 2.University hospital dermatologic...
We prepared concatamers of alpha4 and beta2 subunits for human nicotinic acetylcholine receptors (AChRs), in which the C terminus was linked to N beta2, or vice versa, via a tripeptide sequence repeated 6 12 times, expressed them Xenopus oocytes. Linkage did not substantially alter channel amplitude open-duration. at prevented AChR potentiation by 17-beta-estradiol disruption its binding site. Assembly AChRs from less efficient, but function much more efficient than that unlinked subunits....
Fragile X syndrome (FXS) is the leading cause of both intellectual disability and autism resulting from a single gene mutation. Previously, we characterized cognitive impairments brain structural defects in Drosophila model FXS demonstrated that these were rescued by treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium. A well-documented biochemical defect observed fly mouse models patients low cAMP levels. levels can be regulated mGluR signaling. Herein, demonstrate...
The diversity of protein isoforms arising from alternative splicing is thought to modulate fine-tuning synaptic plasticity. Fragile X mental retardation (FMRP), a neuronal RNA binding protein, exists in as result splicing, but the contribution these neural plasticity are not well understood. We show that two Drosophila melanogaster FMRP (dFMR1) have differential roles mediating development and behavior functions conferred by dfmr1 gene. These differ presence interaction module related prion...
Fragile X is the most common monogenic disorder associated with intellectual disability (ID) and autism spectrum disorders (ASD). Additionally, many patients are afflicted executive dysfunction, ADHD, seizure sleep disturbances. caused by loss of FMRP expression, which encoded FMR1 gene. Both fly mouse models fragile also based on having no functional protein expression their respective homologs. The model displays well defined cognitive impairments structural brain defects model, although...
We characterized the functional and molecular properties of nicotinic acetylcholine receptors (AChRs) expressed by IMR-32, a human neuroblastoma cell line, compared them to α3 AChRs in stably transfected embryonic kidney (HEK) cells. IMR-32 cells, like neurons autonomic ganglia, have been shown express α3, α5, α7, β2, β4 AChR subunits. From these subunits, several types as well homomeric α7 could be formed. However, we show, cells overwhelmingly reflect α3β4 AChRs. function was not detected,...
The genus
Disruption of neuronal signaling by soluble beta-amyloid has been implicated in deficits short-term recall the early stages Alzheimer's disease. One potential target for is synapse, with evidence differential interaction both pre- and post-synaptic elements. Our previous work revealed an agonist-like action (pM to nM) on isolated pre-synaptic terminals increase [Ca(2+)]i, apparent involvement nicotinic receptors. To directly establish role receptors Ca(2+) regulation, we investigated from...
Numerous host and viral factors likely participate in the onset progression of HIV-1-associated dementia (HIVD). Previous studies have suggested that gene expression resident central nervous system (CNS) cells monocyte/macrophage lineage play a role production neurotoxic proteins infectious virus, deregulation cellular expression, and/or dysfunction glial neuronal cell populations. HIV-1 replication is regulated, part, by interactions between transcription trans-activators, Tat protein R...
Metabotropic glutamate receptors (mGluRs) have well-established roles in cognition and social behavior mammals. Whether or not these been conserved throughout evolution from invertebrate species is less clear. Mammals eight mGluRs whereas Drosophila has a single DmGluRA, which both Gi Gq coupled signaling activity. We utilized to examine the role of DmGluRA various phases memory. found that flies are homozygous heterozygous for loss function mutations impaired male Drosophila. Futhermore,...
The steroid and xenobiotic receptor SXR (human pregnane X receptor) is a nuclear that plays key role in the body's detoxification response by regulating genes involved drug metabolism transport. ligands include wide range of compounds, which induce transcription target via activation heterodimeric factor consisting related retinoid (RXR). We investigated effect RXR-selective ligands, rexinoids, on SXR/RXR activity. In agreement with previous reports, we found rexinoids are weak activators...
Abstract The current understanding of mycobacterial cell envelope remodeling in response to antibiotics is limited. Chemical tools that report on phenotypic changes with minimal wall perturbation are critical such time-dependent processes. We employed a fluorogenic chemical probe image how perturb assembly real-time. Time-lapse microscopy revealed differential antibiotic treatment elicited unique cellular phenotypes, providing platform for simultaneously monitoring construction and...
Neuronal nicotinic receptors have been shown to be regulated by soluble beta amyloid. Beta amyloid blocks receptor activation at somatic sites, whereas it activates on presynaptic nerve endings. To characterize the subtype of endings from mouse cortex activated Responses (Abeta) were measured as changes in Ca2+ quantified via confocal imaging individual, isolated various regions cortex, including prefrontal areas. Comparisons made between preparations control mice (wild–type littermates) and...