A5074128852- Cellular transport and secretion
- HIV Research and Treatment
- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Mosquito-borne diseases and control
- Autophagy in Disease and Therapy
- Lysosomal Storage Disorders Research
- Nuclear Structure and Function
- Phagocytosis and Immune Regulation
- Calcium signaling and nucleotide metabolism
- Cannabis and Cannabinoid Research
- Virus-based gene therapy research
- Lipid Membrane Structure and Behavior
- Transgenic Plants and Applications
- Genetics, Aging, and Longevity in Model Organisms
- HIV/AIDS drug development and treatment
- Biochemical and Molecular Research
- Diet and metabolism studies
- Viral Infections and Immunology Research
- Adipose Tissue and Metabolism
- Prion Diseases and Protein Misfolding
- Climate variability and models
- CRISPR and Genetic Engineering
- interferon and immune responses
- Climate Change Policy and Economics
QB3
2021-2024
University of California, Berkeley
1978-2024
Charles River Laboratories (Netherlands)
2024
National Institute of Allergy and Infectious Diseases
2020-2024
National Institutes of Health
2020-2021
John Wiley & Sons (United States)
2016-2020
University of Maryland, College Park
2019
Bioscience Research
2019
The prion-like spread of protein aggregates is a leading hypothesis for the propagation neurofibrillary lesions in brain, including tau inclusions associated with Alzheimer’s disease. mechanisms cellular uptake seeds and subsequent nucleated polymerization cytosolic are major questions field, potential coupling between entry nucleation has been little explored. We found that primary astrocytes neurons, endocytosis leads to their accumulation lysosomes. This turn lysosomal swelling,...
Activation of PINK1 and Parkin in response to mitochondrial damage initiates a that includes phosphorylation RAB7A at Ser72. Rubicon is binding negative regulator autophagy. The structure the Rubicon:RAB7A complex suggests Ser72 would block binding. Indeed, vitro by TBK1 abrogates Pacer, positive autophagy, has an RH domain with basic triad predicted bind introduced phosphate. Consistent this, Pacer-RH binds phosho-RAB7A but not unphosphorylated RAB7A. In cells, depolarization reduces...
Systematic Evolution of Ligands by Exponential Enrichment (SELEX) is the iterative process which nucleic acids that can bind with high affinity and specificity (termed aptamers) to specific protein targets are selected. Using a SELEX protocol adapted for Xeno-Nucleic Acid (XNA) as suitable substrate aptamer generation, 2′-fluoroarabinonucleic acid (FANA) was used select several related aptamers HIV-1 integrase (IN). IN bound FANA equilibrium dissociation constants (KD,app) ∼50–100 pM in...
The endosomal sorting complex required for transport (ESCRT) machinery is centrally involved in the repair of damage to both plasma and lysosome membranes. ESCRT recruitment sites occurs on a fast time scale, Ca2+ has been proposed play key signaling role process. Here, we show that Ca2+-binding regulatory protein ALG-2 binds directly negatively charged membranes Ca2+-dependent manner. Next, by monitoring colocalization ALIX with membranes, recruits membrane. Furthermore, membrane...
Defective mitochondrial quality control in response to loss of membrane polarization is implicated Parkinsons disease by mutations PINK1 and PRKN. Application situ cryo-electron tomography (cryo-ET) made it possible visualize the consequences depolarization at higher resolution than heretofore attainable. Parkin-expressing U2OS cells were treated with depolarizing agents oligomycin antimycin A (OA), subjected cryo-FIB milling, structure was characterized cryo-ET. Phagophores visualized...
Abstract The prion-like spread of protein aggregates is a leading hypothesis for the propagation neurofibrillary lesions in brain, including tau inclusions associated with Alzheimer’s disease. mechanisms cellular uptake seeds and subsequent nucleated polymerization cytosolic are major questions field, potential coupling between entry nucleation has been little explored. We found that primary astrocytes, endocytosis leads to their accumulation lysosomes. This turn lysosomal swelling,...
The Endosomal Sorting Complex Required for Transport (ESCRT) is an evolutionarily conserved machinery that performs reverse-topology membrane scission in cells universally required from cytokinesis to budding of enveloped viruses. Upstream acting ESCRT-I and ALIX control these events link recruitment viral cellular partners late-acting ESCRT-III CHMP4 through incompletely understood mechanisms. Using structure-function analyses combined with super-resolution imaging, we show function as...
SUMMARY Activation of PINK1 and Parkin in response to mitochondrial damage initiates a cytoprotective mitophagy that includes phosphorylation RAB7A at Ser72. Rubicon is binding protein acts as negative regulator autophagy. The structure the Rubicon-RAB7A complex suggests Ser72 would block binding. Indeed, vitro by TBK1 abrogates Pacer, positive autophagy, has an RH domain with basic triad predicted bind introduced phosphate. Consistent this, Pacer-RH binds phosho-RAB7A but not...
Abstract The endosomal sorting complex required for transport (ESCRT) machinery has been shown to be centrally involved in repair of damage both the plasma and lysosome membranes. ESCRT recruitment sites occurs on a fast time scale, Ca 2+ proposed play key signaling role process. Here, we show that -binding regulatory protein ALG-2 binds directly negatively charged membranes -dependent manner. Next, by monitoring colocalization ALIX with membranes, recruits membrane. Furthermore, membrane...