- Neuroscience and Neuropharmacology Research
- Memory and Neural Mechanisms
- Stress Responses and Cortisol
- Cytokine Signaling Pathways and Interactions
- Ubiquitin and proteasome pathways
- Sleep and Wakefulness Research
- Innovations in Medical Education
- Neural dynamics and brain function
- Evaluation of Teaching Practices
- Neonatal Respiratory Health Research
- Neuroscience of respiration and sleep
- Single-cell and spatial transcriptomics
- Immune Cell Function and Interaction
- Cellular transport and secretion
- Genetics and Neurodevelopmental Disorders
- Genetic Syndromes and Imprinting
- interferon and immune responses
- Epigenetics and DNA Methylation
- Problem and Project Based Learning
- Receptor Mechanisms and Signaling
- Education and Critical Thinking Development
- Infant Health and Development
- Innovative Teaching Methods
- Advanced biosensing and bioanalysis techniques
- Zebrafish Biomedical Research Applications
St. Jude Children's Research Hospital
2017-2025
Stanford University
2015-2021
Howard Hughes Medical Institute
2014-2020
University of Houston
1998-2011
University of California, San Diego
2009-2011
Eastern Illinois University
2007
Baylor College of Medicine
1990-1996
Rutgers, The State University of New Jersey
1987
The precise annotation and accurate identification of neural structures are prerequisites for studying mammalian brain function. orientation neurons circuits is usually determined by mapping images to coarse axial-sampling planar reference atlases. However, individual differences at the cellular level likely lead position errors an inability orient projections single-cell resolution. Here, we present a high-throughput precision imaging method that can acquire co-localized brain-wide data set...
A tiny group of neurons in the brainstem matches breathing rate to level calmness versus arousal.
Protein degradation via the ubiquitin proteasome system has been shown to regulate changes in synaptic strength that underlie multiple forms of plasticity. It is plausible, therefore, itself regulated by activity. By utilizing live-cell imaging strategies we report rapid and dynamic regulation hippocampal neurons We find blockade action potentials (APs) with tetrodotoxin inhibited activity proteasome, whereas up-regulation APs bicuculline dramatically increased proteasome. In addition,...
The accurate trafficking of AMPA receptors (AMPARs) to and from the synapse is a critical component learning memory in brain, whereas dysfunction AMPAR hypothesized be an underlying mechanism Alzheimer's disease. Previous work has shown that ubiquitination integral membrane proteins common posttranslational modification used mediate endocytosis endocytic sorting surface eukaryotic cells. Here we report mammalian AMPARs become ubiquitinated response their activation. Using mutant GluA1 unable...
Mosaic analysis with double markers (MADM) offers one approach to visualize and concomitantly manipulate genetically defined cells in mice single-cell resolution. MADM applications include the of lineage, morphology physiology, genomic imprinting phenotypes, dissection cell-autonomous gene functions vivo health disease. Yet, can only be applied <25% all mouse genes on select chromosomes date. To overcome this limitation, we generate transgenic knocked-in cassettes near centromeres 19...
The pituitary peptide hormone prolactin (Prl) is a potent inducer of Nb2 T lymphoma cell proliferation. To analyze the early genetic response to mitogenic signals Prl, cDNA library was constructed from cells stimulated for 4 h with Prl and protein synthesis inhibitor cycloheximide. Of 26 distinct clones isolated by differential screening, one clone, designated c25, exhibited extremely rapid but transient kinetics induction superinduction plus Run-on transcription analysis indicated that c25...
The trafficking of AMPA receptors (AMPARs) to and from synapses is crucial for synaptic plasticity. Previous work has demonstrated that AMPARs undergo activity-dependent ubiquitination by the E3 ubiquitin ligase Nedd4-1, which promotes their internalization degradation in lysosomes. Here, we define molecular mechanisms involved deubiquitination AMPARs. We report Nedd4-1 rapidly redistributed dendritic spines response AMPAR activation not NMDA receptor (NMDAR) cultured rat neurons. In...
Abstract Chronic psychosocial stress markedly reduces the expression of high‐frequency stimulation (HFS)‐evoked early long‐term potentiation (LTP) in CA1 region hippocampus anesthetized rats. Immunoblotting was performed to determine changes molecular levels key signaling proteins that might be responsible for this inhibitory effect. Western blot analysis demonstrates chronic decreases basal calcium calmodulin kinase II (CaMKII), phosphorylated (P)‐CaMKII, calmodulin, and protein C (PKCγ)...
Emotions are distinct patterns of behavioral and physiological responses triggered by stimuli that induce different brain states. Elucidating the circuits is difficult because challenges in interrogating emotional states their complex outputs. Here, we leverage recent discovery mice a neural circuit for sighing, simple, quantifiable output various emotions. We show mouse confinement triggers this "claustrophobic" but not accompanying tachypnea, requires same medullary neuromedin B...
Aerosol delivery of gene therapy for treatment lung diseases allows topical the airways with DNA concentrations not obtainable by systemic administration. We have investigated cationic liposomes complexed to plasmid in a small particle aerosol. Plasmid cDNA–DMRIE/DOPE complexes were nebulized using either an Aerotech II or Puritan-Bennett 1600 (PB1600) nebulizer. Reservoir sampling showed that DNA–DMRIE/DOPE damaged significant degree during nebulization, such activity transfected was...
Abstract Aim Physiological functions in mammals show circadian oscillations, synchronized by daily cycles of light and temperature. Central peripheral clocks participate this regulation. Since the ion channel TRPM8 is a critical cold sensor, we investigated its role function. Methods We used reporter mouse lines TRPM8‐deficient mice. mRNA levels were determined situ hybridization or RT‐qPCR protein immunofluorescence. A telemetry system was to measure core body temperature (Tc). Results...
Breathing, and the motor circuits that control it, is essential for life. At core of respiratory are Dbx1-derived interneurons, which generate rhythm pattern breathing, phrenic neurons (MNs), provide final output drives diaphragm muscle contractions during inspiration. Despite their critical function, principles dictate how assemble unknown. Here, we show coordinated activity a type I cadherin (N-cadherin) II cadherins (Cadherin-6, -9, -10) required in both MNs to robust output. Both MN-...
The anti-mitotic drugs colchicine and paclitaxel increase transfection efficiency of cationic liposomes. Using combined lipid-mediated with agents for gene therapy cancer has been limited due to the likely development multi-drug resistance (MDR). We treated human cell lines normal liver cells glucocorticoids in combination antimitotics or before transient, transfection. Colchicine each enhanced transgene expression several lines. Moreover, glucocorticoid, colchicine, significantly increased...
Potentiation was originally demonstrated as a nonadditive, synergistic enhancement of interferon (IFN) activity in the mouse system for mixed preparations containing MuIFNα/β and MuIFN-γ. antiviral anticellular activities has now been studied human systems, both systems IFN-α IFN-β interacted synergistically with IFN-γ, but not each other. Further, were potentiated equally by IFN-γ. HuIFNs specific 107 U/mg protein higher. Naturally produced recombinant HuIFN-αs had same relative abilities...