A5074127520- Virus-based gene therapy research
- CAR-T cell therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Research and Treatments
- Cellular transport and secretion
- Prenatal Substance Exposure Effects
- Ion channel regulation and function
- Microtubule and mitosis dynamics
- Neuroscience and Neuropharmacology Research
- Genetic Neurodegenerative Diseases
- Planarian Biology and Electrostimulation
- Cannabis and Cannabinoid Research
- Herpesvirus Infections and Treatments
- Nicotinic Acetylcholine Receptors Study
- Ubiquitin and proteasome pathways
- RNA Interference and Gene Delivery
- Migraine and Headache Studies
- Birth, Development, and Health
- Neurogenesis and neuroplasticity mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- Mitochondrial Function and Pathology
- Developmental Biology and Gene Regulation
- Neuroscience of respiration and sleep
- Invertebrate Immune Response Mechanisms
- 14-3-3 protein interactions
University of Colorado Anschutz Medical Campus
2015-2024
Cardiff University
2020-2023
University of Colorado Denver
2015-2023
University of Sussex
2020
Neurotrack Technologies (United States)
2019
University of Washington
2016
Seattle University
2016
Brigham Young University
2005-2013
University of California, San Francisco
2013
Massachusetts General Hospital
2002-2007
We observe previously unknown interactions between clinically important adenovirus vector capsids, platelet factor 4, and CAR.
Mutations in casein kinase Iδ that are associated with migraine patients cause changes enzymatic function, pain behavior, cortical excitability, and astrocyte signaling mice.
BackgroundThe prolonged time course of Huntington's disease (HD) neurodegeneration increases both the and cost testing potential therapeutic compounds in mammalian models. An alternative is to initially assess efficacy invertebrate models, reducing from months days.Methodology/Principal FindingsWe screened candidate that were identified previously cell culture/animal studies a C. elegans HD model found two FDA approved drugs, lithium chloride mithramycin, independently combination suppressed...
Mutations that disrupt function of the human inwardly rectifying potassium channel KIR2.1 are associated with craniofacial and digital defects Andersen-Tawil Syndrome, but contribution Kir channels to development is undefined. Deletion mouse Kir2.1 also causes cleft palate defects. These strikingly similar phenotypes result from disrupted TGFβ/BMP signaling. We use Drosophila melanogaster show a homolog, Irk2, affects by disrupting BMP Phenotypes irk2 deficient lines, mutant allele, siRNA...
Expansion of a polyglutamine tract in the huntingtin protein causes neuronal degeneration and death Huntington's disease patients, but molecular mechanisms underlying polyglutamine-mediated cell remain unclear. Previous studies suggest that expanded tracts alter transcription by sequestering glutamine rich transcriptional regulatory proteins, thereby perturbing their function. We tested this hypothesis Caenorhabditis elegans neurons expressing human fragment with an (Htn-Q150). Loss function...
Microtubules are dynamic cytoskeletal polymers that mediate numerous, essential functions such as axon and dendrite growth neuron migration throughout brain development. In recent years, sequencing has revealed dominant mutations disrupt the tubulin protein building blocks of microtubules. These lead to a spectrum devastating malformations, complex neurological physical phenotypes, even fatality. The most common gene mutated is α-tubulin TUBA1A, which prevalent expressed in post-mitotic...
Background: Prenatal exposure to cannabis may influence childhood cognition and behavior, but the epidemiologic evidence is mixed. Even less known about potential impact of secondhand during early childhood. Objective: This study sought assess whether prenatal and/or postnatal was associated with behavior. Study design: sub-study included a convenience sample 81 mother–child pairs from Colorado-based cohort. Seven common cannabinoids (including delta 9-tetrahydrocannabinol (Δ9-THC)...
Huntington's disease is a progressive neurodegenerative caused by polyglutamine (polyQ) repeat expansion in the huntingtin protein [Huntington's Disease Collaborative Research Group (1993) Cell 72, 971–983]. To understand mechanism which polyQ repeats cause neurodegeneration and cell death, we modeled neurotoxicity Caenorhabditis elegans. In our model, expression of N-terminal fragments human causes polyQ-dependent degeneration neurons. We conducted genetic screen to identify proteins that...
During morphogenesis, cells communicate with each other to shape tissues and organs. Several lines of recent evidence indicate that ion channels play a key role in cellular signaling tissue morphogenesis. However, little is known about the scope specific ion-channel types impinge upon developmental pathways. The Drosophila melanogaster wing an excellent model which address this problem as vein patterning acutely sensitive changes We conducted screen 180 expressed using loss-of-function...
Abstract The microtubule cytoskeleton supports diverse cellular morphogenesis and migration processes during brain development. Mutations in tubulin genes are associated with severe human malformations known as ‘tubulinopathies’; however, it is not understood how molecular-level changes subunits lead to malformations. In this study, we demonstrate that missense mutations affecting arginine at position 402 (R402) of TUBA1A α-tubulin selectively impair dynein motor activity severely dominantly...
Glioblastoma (GBM) is the most common and aggressive adult brain cancer with an average survival rate of around 15 months in patients receiving standard treatment. Oncolytic adenovirus expressing therapeutic transgenes represent a promising alternative treatment for GBM. Of many human adenoviral serotypes described to date, 5 (HAdV-C5) has been utilised clinically experimentally. However, use Ad5 as anti-cancer agent may be hampered by naturally high seroprevalence rates HAdV-C5 coupled...
Lip movements were examined across several repetitive speaking conditions (speech alone and concurrently with a linguistic, cognitive, or visuomotor challenge task) in 20 young adults. Performance these nonspeech activities was also compared between isolated tasks concurrent speech conditions. Linguistic challenges resulted increased spatiotemporal variability of lip displacement repetitions. Motor led to more rapid smaller displacement. These qualitatively different changes suggest that...
Objective: Frequency lowering (FL) strategies move high frequency sound into a lower range. This study determined if speech perception differences are observed between some of the different that available. Design: A cross-sectional, repeated-measures design was used to compare three hearing aids wide-dynamic range compression (WDRC) and either non-linear (NFC), linear transposition (LFT), or translation (FT). The were matched prescriptive real ear targets for WDRC. settings each FL strategy...
Newly born neurons express high levels of TUBA1A α-tubulin to assemble microtubules for neurite extension and provide tracks intracellular transport. In the adult brain, Tuba1a expression decreases dramatically. A mouse that harbors a loss-of-function mutation in gene encoding (Tuba1aND/+ ) allows us ask whether is important function mature neurons. α-Tubulin are about half wild type juvenile Tuba1aND/+ brains, but close normal older animals. postnatal day (P)0 cultured neurons, reduced...
Developing neurons undergo dramatic morphological changes to appropriately migrate and extend axons make synaptic connections. The microtubule cytoskeleton, made of α/β-tubulin dimers, drives neurite outgrowth, promotes neuronal growth cone responses, facilitates intracellular transport critical cargoes during neurodevelopment. TUBA1A constitutes the majority α-tubulin in developing brain mutations humans cause severe malformations accompanied by varying neurological defects, collectively...
TGF-beta (transforming growth factor-beta-) mediated signal transduction affects and patterning in a variety of organisms. Here we report genetic characterization the Drosophila punt gene that encodes type II serine/threonine kinase TGF-beta/Dpp (Decapentaplegic) receptor. Although was originally identified based on its requirement for embryonic dorsal closure, have documented multiple periods activity throughout life cycle. We demonstrate potentially related phenotypes, defects dorsoventral...
Adenoviruses are powerful tools experimentally and clinically. To maximize efficacy, the development of serotypes with low preexisting levels immunity in population is desirable.