A5029191260- Neurobiology and Insect Physiology Research
- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Ion channel regulation and function
- Nicotinic Acetylcholine Receptors Study
- Developmental Biology and Gene Regulation
- Genetics, Aging, and Longevity in Model Organisms
- Retinal Development and Disorders
- Cancer Research and Treatments
- Cancer-related Molecular Pathways
- Adenosine and Purinergic Signaling
- Receptor Mechanisms and Signaling
- DNA Repair Mechanisms
- Virus-based gene therapy research
- Genetics and Neurodevelopmental Disorders
- Microtubule and mitosis dynamics
- Endoplasmic Reticulum Stress and Disease
- MicroRNA in disease regulation
- Nerve injury and regeneration
- RNA Research and Splicing
- Pluripotent Stem Cells Research
- Circular RNAs in diseases
- Ubiquitin and proteasome pathways
- Protein Kinase Regulation and GTPase Signaling
- Congenital heart defects research
Buck Institute for Research on Aging
2016-2024
McGill University
1996-2022
University of Southern California
2022
Sidney Kimmel Cancer Center
1999-2007
Vanderbilt University
2007
Centre National de la Recherche Scientifique
2007
University of California, Berkeley
2001-2004
Howard Hughes Medical Institute
2001-2002
University of California, San Diego
1997
Montreal Neurological Institute and Hospital
1996
Schizophrenia likely results from poorly understood genetic and environmental factors. We studied the gene encoding synaptic protein SHANK3 in 285 controls 185 schizophrenia patients with unaffected parents. Two de novo mutations (R1117X R536W) were identified two families, one being found three affected brothers, suggesting germline mosaicism. Zebrafish rat hippocampal neuron assays revealed behavior differentiation defects resulting R1117X mutant. As previously reported autism, occurrence...
We have studied the role of Jun/stress-activated protein kinase (JNK/SAPK) pathway in DNA repair and cisplatin resistance T98G glioblastoma cells. JUN/SAPK is activated by damage phosphorylates serines 63 73 N-terminal domain c-Jun, which known to increase its transactivation properties. show that treatment cells with but not transplatin isomer activates JNK/SAPK about 10-fold. cells, are highly resistent (IC50 = 140 ± 13 μm), modified express a nonphosphorylatable dominant negative c-Jun...
SummaryHomeostatic mechanisms operate to stabilize synaptic function; however, we know little about how they are regulated. Exploiting Drosophila genetics, have uncovered a critical role for the target of rapamycin (TOR) in regulation homeostasis at larval neuromuscular junction. Loss postsynaptic TOR disrupts retrograde compensatory enhancement neurotransmitter release that is normally triggered by reduction glutamate receptor activity. Moreover, overexpression or phosphomimetic form S6...
Programmed cell death is an ongoing process in both the developing and mature nervous system. The tumor suppressor gene, p53, can induce apoptosis a number of different types. Recently, enhanced expression p53 has been observed during acute neurological disease. To determine whether overexpression could influence neuronal survival, we used recombinant adenovirus vector carrying wild type to transduce postmitotic neurons. A control consisting same background but lacZ reporter cassette was...
A common feature of neuronal nicotinic acetylcholine receptors (nAChRs) is that they conduct inward current at negative membrane potentials but little outward positive potentials, a property referred to as rectification. Physiologically, rectification serves important functions, and the main goal our study was investigate mechanisms underlying these receptors. We examined recombinant α 3 β 4 2 nAChR subtypes expressed in Xenopus oocytes native nAChRs on superior cervical ganglion (SCG)...
miR-124 is conserved in sequence and neuronal expression across the animal kingdom predicted to have hundreds of mRNA targets. Diverse defects neural development function were reported from antisense studies vertebrates, but a nematode knockout mir-124 surprisingly lacked detectable phenotypes. To provide genetic insight Drosophila, we deleted its single locus found that it dispensable for gross aspects specification differentiation. On other hand, detected variety mutant phenotypes...
Abstract Parkinson’s disease gene leucine-rich repeat kinase 2 (LRRK2) has been implicated in a number of processes including the regulation mitochondrial function, autophagy and endocytic dynamics; nevertheless, we know little about its potential role synaptic plasticity. Here demonstrate that postsynaptic knockdown fly homologue LRRK2 thwarts retrograde, homeostatic compensation at larval neuromuscular junction. Conversely, overexpression either or human transgene induces retrograde...
Many nicotinic acetylcholine receptors (nAChRs) expressed by central neurons are located at presynaptic nerve terminals. These have high calcium permeability and exhibit strong inward rectification, two important physiological features that enable them to facilitate transmitter release. Previously, we showed intracellular polyamines act as gating molecules block neuronal nAChRs in a voltage-dependent manner, leading rectification. Our goal is identify the structural determinants underlie...
We have developed an open-source software for neuroscientists to analyze electrophysiological recordings. Named SimplyFire, the gives users flexibility a variety of recordings using interactive graphical user interface or as importable Python package. The features simple plugin structure that allows create and deploy various electrophysiology analysis tools. SimplyFire is pre-packaged with tools commonly used in electrophysiology, such noise filtering, trace averaging, miniature analysis,...
Pathogenic mutations in leucine-rich repeat kinase 2 (LRRK2) induce an age-dependent loss of dopaminergic (DA) neurons. We have identified Furin 1, a pro-protein convertase, as translational target LRRK2 DA Transgenic knockdown Furin1 or its substrate the bone morphogenic protein (BMP) ligand glass bottom boat (Gbb) protects against LRRK2-induced enhances accumulation phosphorylated Mad (pMad) nuclei glial cells vicinity neurons but not Consistently, exposure to paraquat 1 levels and induces...
Retrograde signaling is essential for neuronal growth, function and survival; however, we know little about how endosomes might be directed from synaptic terminals onto retrograde axonal pathways. We have identified Khc-73, a plus-end microtubule motor protein, as regulator of sorting in Drosophila larval neurons. The number boutons the amount neurotransmitter release at Khc-73 mutant neuromuscular junction (NMJ) are normal, but find significant decrease presynaptic sites. This defect larvae...
5-Hydroxytryptamine3 (5-HT3) receptors are the only known monoamine mediating fast excitatory responses in mammalian neurons. Their primary structure as well their electrophysiological and pharmacological properties show a phylogenetic relation to nicotinic acetylcholine, GABAA, glycine receptors. As prototypical member of this gene superfamily, we investigated membrane topology functional homomeric 5-HT3 by using epitope tagging channel subunits expressed heterologous systems. Visualization...