A5077631650- Genetic and Kidney Cyst Diseases
- Protist diversity and phylogeny
- Microtubule and mitosis dynamics
- Mitochondrial Function and Pathology
- Renal and related cancers
- Nerve injury and regeneration
- Neuroscience and Neuropharmacology Research
- Developmental Biology and Gene Regulation
- Molecular Sensors and Ion Detection
- Microbial Community Ecology and Physiology
- Trace Elements in Health
- Advanced Fluorescence Microscopy Techniques
- Cholinesterase and Neurodegenerative Diseases
- Methane Hydrates and Related Phenomena
- Parasitic Infections and Diagnostics
- Cellular transport and secretion
- EEG and Brain-Computer Interfaces
- Cardiac Arrest and Resuscitation
- Glycosylation and Glycoproteins Research
- ATP Synthase and ATPases Research
- Face Recognition and Perception
- Photosynthetic Processes and Mechanisms
- Circadian rhythm and melatonin
- Alzheimer's disease research and treatments
- Hedgehog Signaling Pathway Studies
Western Washington University
2021-2024
University of Colorado Anschutz Medical Campus
2014-2018
University of Colorado Boulder
2012-2016
University of Colorado Denver
2014-2016
University of Pennsylvania
2006-2009
University of Campania "Luigi Vanvitelli"
2002
Mitochondrial dysfunction is one of the major intracellular lesions Alzheimer’s disease (AD). However, causative factors involved in mitochondrial human AD are not well understood. Here we report that nonglycosylated full-length and C-terminal truncated amyloid precursor protein (APP) accumulates exclusively import channels mitochondria brains but age-matched controls. Furthermore, brains, mitochondrially associated APP formed stable ∼480 kDa complexes with translocase outer membrane 40...
Zinc (Zn(2+)) homeostasis plays a vital role in cell function, and the dysregulation of intracellular Zn(2+) is associated with mitochondrial dysfunction. Few tools exist to quantitatively monitor buffered, free concentration mitochondria living cells ([Zn(2+)](mito)). We have validated three high dynamic range, ratiometric, genetically encoded, fluorescent sensors that we successfully used precisely measure [Zn(2+)](mito) several types. Using one these sensors, called mito-ZapCY1, report...
Fluorescent sensors are powerful tools for visualizing and quantifying molecules ions in living cells. A variety of small molecule genetically encoded have been developed studying intracellular Zn2+ homeostasis signaling, but no direct comparisons exist, making it challenging researchers to identify the appropriate sensor a given application. Here we directly compare widely used probe FluoZin-3 sensor, ZapCY2. We demonstrate that, contrast FluoZin-3, ZapCY2 exhibits well-defined cytosolic...
Cilia, essential motile and sensory organelles, have several compartments: the basal body, transition zone, middle distal axoneme segments. The segment accommodates key functions, including cilium assembly activities. While contains doublet microtubules (incomplete B-tubules fused to complete A-tubules), only A-tubule extensions, its existence requires coordination of microtubule length at nanometer scale. We show that three conserved proteins, two which are mutated in ciliopathy Joubert...
CcO (cytochrome c oxidase) is a multisubunit bigenomic protein complex which catalyses the last step of mitochondrial electron transport chain. The nuclear-encoded subunits are thought to have roles either in regulation or structural stability enzyme. Subunit Vb peripheral subunit mammalian that dramatically reduced under hypoxia. Although it has been shown contain different ligand-binding sites and undergo modifications, its precise function not known. In present study we generated cell...
We have mapped the sites of ischemia/reperfusion‐induced phosphorylation cytochrome c oxidase (CcO) subunits in rabbit hearts by using a combination Blue Native gel/Tricine gel electrophoresis and nano‐LC–MS/MS approaches. used precursor ion scanning combined with neutral loss found that mature CcO subunit I was phosphorylated at tandem Ser115/Ser116 positions, IVi1 Thr52 Vb Ser40. These are highly conserved mammalian species. Molecular modeling suggests face inter membrane space while those...
Dendritic spines are major sites of excitatory synaptic transmission and changes in their numbers morphology have been associated with neurodevelopmental neurodegenerative disorders. Brain-derived Neurotrophic Factor (BDNF) is a secreted growth factor that influences hippocampal, striatal neocortical pyramidal neuron dendritic spine density. However, the mechanisms by which BDNF regulates how interacts other regulators remain unclear. We propose one mechanism promotes formation through an...
Cilia-organizing basal bodies (BBs) are microtubule scaffolds that visibly asymmetrical because they have attached auxiliary structures, such as striated fibers. In multiciliated cells, BB orientation aligns to ensure coherent ciliary beating, but the mechanisms maintain unclear. For first time in Tetrahymena thermophila, we use comparative whole-genome sequencing identify mutation disorientation mutant disA-1. disA-1 abolishes localization of novel protein DisAp T. thermophila fibers...
Protein kinase A (PKA) activation has been implicated in early-phase ischemic preconditioning. We recently found that during ischemia PKA causes inactivation of cytochrome- c oxidase (CcO) and contributes to myocardial damage due ischemia-reperfusion. It may be β-adrenergic stimulation via endogenous catecholamine release activates PKA. Thus mediate both protection ischemia. The present studies were designed determine the role β 1 -adrenergic receptor (β -AR) Langendorff-perfused rabbit...
Basal bodies are radially symmetric, microtubule-rich structures that nucleate and anchor motile cilia. Ciliary beating produces asymmetric mechanical forces resisted by basal bodies. To resist these forces, distinct regions within the body ultrastructure microtubules themselves must be stable. However, molecular components stabilize remain poorly defined. Here, we determine Fop1 functionally interacts with established stability Bld10 Poc1. We find microtubule glutamylation incorporate into...
The transition of dividing neuroepithelial progenitors to differentiated neurons and glia is essential the formation a functional nervous system. Sonic Hedgehog (Shh) mitogen for spinal cord progenitors, but how cells become insensitive proliferative effects Shh not well understood. Because reception occurs at primary cilia, which are positioned within apical membrane we hypothesized that loss characteristics reduces signaling response, causing cell cycle exit differentiation. We tested this...
Visualizing fluorescence-tagged molecules is a powerful strategy that can reveal the complex dynamics of cell. One robust and broadly applicable method immunofluorescence microscopy, in which fluorescence-labeled antibody binds molecule interest then location determined by fluorescence microscopy. The effective application this technique includes several considerations, such as nature antigen, specificity antibody, permeabilization fixation specimen, imaging Although each protocol will...
ABSTRACT Multi-ciliated cells (MCCs) use polarized fields of undulating cilia (ciliary array) to produce fluid flow that is essential for many biological processes. Cilia are positioned by microtubule scaffolds called basal bodies (BBs) arranged within a spatially complex 3-dimensional geometry (3D). Here, we develop robust and automated computational image analysis routine quantify 3D BB organization in the ciliate, Tetrahymena thermophila. Using this routine, generate first morphologically...
Brain-derived neurotrophic factor (BDNF) regulates both action potential (AP) generation and neuron morphology. However, whether BDNF-induced changes in morphology directly impact AP is unclear. We quantified BDNF's effect on cultured cortical morphological parameters found that BDNF stimulates dendrite growth addition of dendrites while increasing excitatory inhibitory presynaptic inputs a spatially restricted manner. To gain insight into how these combined structure synaptic input...
Endogenous RNA interference (RNAi) pathways regulate a wide range of cellular processes in diverse eukaryotes, yet the ciliated eukaryote, Tetrahymena thermophila, purpose RNAi that generate ∼23-24 nucleotide (nt) small (s)RNAs has remained unknown. Here, we investigated phenotypic and gene expression impacts on vegetatively growing cells when genes involved nt sRNA biogenesis are disrupted. We observed slower proliferation increased DNA metabolism chromosome organization maintenance mutants...
Human immunodeficiency virus (HIV) infection is characterized by a severe depletion of both CD4+ and CD8+ T cells, representing the result virus-mediated killing infected lymphocytes programmed cell death (apoptosis) uninfected bystander cells. Since only small fraction are depleted viral killing, apoptosis represents one most important mechanism during HIV infection. Several apoptotic pathways can be triggered different stimuli: persistent lymphocyte activation; altered receptor (Fas,...
ABSTRACT Caenorhabditis elegans gut and cuticle produce a disruptive amount of autofluorescence during imaging. Although C. has been characterized, it not characterized at high resolution using both spectral fluorescence lifetime-based approaches. We performed scans whole, living animals to characterize adult elegans. By scanning 405 nm, 473 561 647 nm excitations, we produced profiles that confirm the brightest clear overlap with emission green fluorescent protein (GFP). then used lifetime...