Joseph J. Lebowitz

ORCID: 0000-0002-2923-7103
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About
Contact & Profiles
Research Areas
  • Neuroscience and Neuropharmacology Research
  • Receptor Mechanisms and Signaling
  • Neurotransmitter Receptor Influence on Behavior
  • Neurological disorders and treatments
  • Pancreatic function and diabetes
  • Parkinson's Disease Mechanisms and Treatments
  • Endoplasmic Reticulum Stress and Disease
  • Heavy Metal Exposure and Toxicity
  • Neural dynamics and brain function
  • Nerve injury and regeneration
  • Trace Elements in Health
  • Diabetes and associated disorders
  • Neuroscience and Neural Engineering
  • Memory and Neural Mechanisms
  • Electrochemical Analysis and Applications
  • Ion channel regulation and function
  • Photoreceptor and optogenetics research
  • Cancer Cells and Metastasis
  • Nicotinic Acetylcholine Receptors Study
  • 3D Printing in Biomedical Research
  • Histone Deacetylase Inhibitors Research
  • Epigenetics and DNA Methylation
  • Neuropeptides and Animal Physiology
  • Pharmacological Receptor Mechanisms and Effects
  • Axon Guidance and Neuronal Signaling

Vollum Institute
2021-2025

Oregon Health & Science University
2021-2025

New York University
2025

NYU Langone Health
2024

University of Florida
2017-2022

VA Portland Health Care System
2022

Case Western Reserve University
2022

University of Colorado Anschutz Medical Campus
2022

New York University Abu Dhabi
2022

University of Michigan
2022

Dopamine neurotransmission is highly dysregulated by the psychostimulant methamphetamine, a substrate for dopamine transporter (DAT). Through interactions with DAT, methamphetamine increases extracellular levels in brain, leading to its rewarding and addictive properties. Methamphetamine also interacts sigma-1 receptor (σ1R), an inter-organelle signaling modulator. Using complementary strategies, we identified novel mechanism σ1R regulation of response methamphetamine. We found that...

10.1038/s41467-017-02087-x article EN cc-by Nature Communications 2017-12-14

Abstract The motor symptoms of Parkinson’s Disease are attributed to the degeneration dopamine neurons in substantia nigra pars compacta (SNc). Previous work MCI-Park mouse model has suggested that loss somatodendritic transmission predicts development deficits. In current study, brain slices from mice were used investigate signaling SNc prior and through onset movement Electrophysiological properties impaired by p30 somatic volume was decreased at all time points. D2 receptor activated...

10.1038/s41531-025-00873-9 article EN cc-by npj Parkinson s Disease 2025-01-29

Manganese exposure produces Parkinson9s-like neurologic symptoms, suggesting a selective dysregulation of dopamine transmission. It is unknown, however, how manganese accumulates in dopaminergic brain regions or it regulates the activity neurons. Our <i>in vivo</i> studies male C57BLJ mice suggest that neurons VTA and substantia nigra via nifedipine-sensitive Ca<sup>2+</sup> channels. channel-mediated current, which increases neurotransmitter release rhythmic firing These are prevented by...

10.1523/jneurosci.2830-19.2020 article EN Journal of Neuroscience 2020-06-23

The videofluoroscopic swallow study (VFSS) is an evaluation of the anatomy and physiology swallowing, often includes a screening esophagus. How esophageal screen translates to pathology remains unknown. purpose this was determine if abnormal clearance (EC) on VFSS correlates with function high-resolution manometry (HREM). This retrospective review 115 adult patients who underwent both HRM. EC scored modified barium impairment profile (MBSImP) component 17. Motility characterized using HRM...

10.1002/lary.32157 article EN The Laryngoscope 2025-03-29

Pulmonary hypertension (PH) is a devastating disease and its successful treatment remains to be accomplished despite recent advances in pharmacotherapy. It has been proposed that PH considered as systemic disease, rather than primarily of the pulmonary vasculature. Consequently, an investigation intricate interplay between multiple organs such brain, vasculature, lung could lead identification new targets for therapy. However, little known about this interplay. This study was undertaken...

10.1161/hypertensionaha.118.10934 article EN Hypertension 2018-04-30

Dopamine neurons switch from tonic pacemaker activity to high-frequency bursts in response salient stimuli. These lead superlinear increases dopamine release, and the degree of this increase is highly dependent on firing frequency. The superlinearity frequency dependence release implicate short-term plasticity processes. presynaptic Ca 2+ -sensor synaptotagmin-7 (SYT7) has suitable properties mediate such been implicated regulating somatodendritic compartments. Here, we use a genetically...

10.1523/eneuro.0501-23.2024 article EN cc-by-nc-sa eNeuro 2024-02-16

Pathophysiological damages and loss of function dopamine neurons precede their demise contribute to the early phases Parkinson's disease. The presence aberrant intracellular pathological inclusions protein α-synuclein within ventral midbrain dopaminergic is one cardinal features We employed molecular biology, electrophysiology, live-cell imaging investigate how excessive expression alters multiple characteristics neuronal dynamics transmission in cultured conditionally expressing GCaMP6f....

10.1038/s41531-021-00210-w article EN cc-by npj Parkinson s Disease 2021-08-18

Histone deacetylase 6 (HDAC6) is an emerging therapeutic target that overexpressed in glioblastoma when compared to other HDACs. HDAC6 catalyzes the deacetylation of alpha-tubulin and mediates disassembly primary cilia, a process required for cell cycle progression. inhibition disrupts glioma proliferation, but whether this effect dependent on tumor cilia unknown. We found inhibitors ACY-1215 (1215) ACY-738 (738) inhibited proliferation multiple patient-derived mouse cells. While both...

10.3390/cancers13071644 article EN Cancers 2021-04-01

Abstract Methamphetamine (METH) is a highly addictive psychostimulant that causes long-lasting effects in the brain and increases risk of developing neurodegenerative diseases. The cellular molecular METH are functionally linked to alterations glutamate levels. Despite well-documented on neurotransmission, underlying mechanism by which alters levels not clearly understood. In this study, we report an essential role proline biosynthesis maintaining METH-induced homeostasis. We observed acute...

10.1038/s41598-020-80917-7 article EN cc-by Scientific Reports 2021-01-14

In many tissues, cell type varies over single-cell length-scales, creating detailed heterogeneities fundamental to physiological function. To gain understanding of the relationship between tissue function and structure, eventually engineer structurally physiologically accurate we need ability assemble 3D cellular structures having level detail found in living tissue. Here introduce a method assembly precision finer than scale. With this create patterns, demonstrating that can be varied scale...

10.1039/d2sm01013e article EN Soft Matter 2022-01-01

Modes of somatodendritic transmission range from rapid synaptic signaling to protracted regulation over distance. Somatodendritic dopamine secretion in the midbrain leads D2 receptor-induced modulation neurons on timescale seconds. Temporally imprecise release mechanisms are often presumed be at play, and previous work indeed suggested roles for slow Ca2+ sensors. We here use mouse genetics whole-cell electrophysiology establish that fast sensor synaptotagmin-1 (Syt-1) is important release....

10.1016/j.celrep.2022.111915 article EN cc-by Cell Reports 2022-12-30

Hilar mossy cells (MCs) are principal excitatory neurons of the dentate gyrus (DG) that play critical roles in hippocampal function and have been implicated brain disorders such as anxiety epilepsy. However, mechanisms by which MCs contribute to DG disease poorly understood. A defining feature is promoter activity dopamine D2 receptor (D2R) gene ( Drd2 ), previous work indicates a key role for dopaminergic signaling DG. Additionally, involvement D2R cognition neuropsychiatric conditions well...

10.1073/pnas.2307509120 article EN cc-by-nc-nd Proceedings of the National Academy of Sciences 2023-12-08

Chronic treatment of animals with morphine results in a long lasting cellular tolerance the locus coeruleus and alters kinase dependent desensitization opioid nonopioid G protein–coupled receptors (GPCRs). This study examined development altered regulation activity after chronic clinically relevant opioids that differ efficacy at <i>µ</i>-opioid (MOR). In slices from oxycodone treated animals, no to was observed when measuring MOR induced increase potassium conductance, but protein receptor...

10.1124/molpharm.121.000453 article EN Molecular Pharmacology 2022-02-22

The ventral midbrain supports a variety of functions through the heterogeneity neurons. Dopaminergic and GABA neurons within this region are particularly susceptible targets amphetamine-class psychostimulants such as methamphetamine. While has been evidenced single-neuron methods, it remains unclear whether to what extent local neuronal network is affected if so, by which mechanisms. Both GABAergic dopaminergic were heavily featured primary model system. Using spontaneous calcium activity,...

10.1371/journal.pone.0222957 article EN cc-by PLoS ONE 2019-09-19

Type 1 diabetes (T1D) has a multifactorial autoimmune etiology, involving environmental prompts and polygenic predisposition. We hypothesized that pancreata from individuals with at risk for T1D would exhibit dysregulated expression of genes associated monogenic forms caused by nonredundant single-gene mutations. Using “monogenetic transcriptomic strategy,” we measured the these in human T1D, autoantibody-positive (autoantibody+), control pancreas tissues real-time quantitative PCR...

10.2337/db21-0070 article EN Diabetes 2021-05-25

Hilar mossy cells (MCs) are principal excitatory neurons of the dentate gyrus (DG) that play critical roles in hippocampal function and have been implicated brain disorders such as anxiety epilepsy. However, mechanisms by which MCs contribute to DG disease poorly understood. Expression from dopamine D2 receptor (D2R) gene (

10.1101/2023.05.05.539468 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2023-05-05

Background: Advances in endoscopic endonasal approaches to the ventral skull base surgery have led increasingly complex resections and defects requiring reconstruction. The ultimate goals of reconstruction are separate sinonasal intracranial compartments prevent postoperative complications such as cerebrospinal fluid (CSF) leaks meningitis. Multiple techniques been reported literature for repair following surgery. While nasal packing is commonly used bolster these reconstructions, there few...

10.1055/s-0044-1779910 article EN Journal of Neurological Surgery Part B Skull Base 2024-02-01

To better characterize the cochlear apex in relation to surgically relevant landmarks guide surgeons and improve procedural success of apical electrode placement.

10.1097/ono.0000000000000060 article EN cc-by Otology & Neurotology Open 2024-08-23

Psychosis is a hallmark of schizophrenia. It typically emerges in late adolescence and associated with dopamine abnormalities aberrant salience. Most genes schizophrenia risk involve ubiquitous targets that may not explain delayed emergence dopaminergic disruptions. This includes

10.1101/2024.10.28.620713 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2024-10-28
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