A5076988745- Microtubule and mitosis dynamics
- Cellular transport and secretion
- Photosynthetic Processes and Mechanisms
- Fungal and yeast genetics research
- Protist diversity and phylogeny
- Genomics and Chromatin Dynamics
- Cellular Mechanics and Interactions
- Parkinson's Disease Mechanisms and Treatments
- RNA Research and Splicing
- Molecular Biology Techniques and Applications
- Cell Image Analysis Techniques
- Plant and fungal interactions
- Intraperitoneal and Appendiceal Malignancies
- 3D Printing in Biomedical Research
- Advanced MRI Techniques and Applications
- Advanced Electron Microscopy Techniques and Applications
- Interdisciplinary Research and Collaboration
- Endoplasmic Reticulum Stress and Disease
- Advanced Fluorescence Microscopy Techniques
- Kruppel-like factors research
- Genetics, Bioinformatics, and Biomedical Research
- Streptococcal Infections and Treatments
- Plant and Fungal Interactions Research
- Cancer Cells and Metastasis
- Cancer Treatment and Pharmacology
UC San Diego Health System
2025
University of California, San Diego
2021-2024
Aligning Science Across Parkinson's
2023-2024
Drexel University
2014-2019
University of California, Berkeley
2018
Organogenesis and tumor metastasis involve the transformation of epithelia to highly motile mesenchymal-like cells. Septins are filamentous G proteins, which overexpressed in metastatic carcinomas, but their functions epithelial motility unknown. Here, we show that a novel network septin filaments underlies organization transverse arc radial (dorsal) stress fibers at leading lamella migrating renal epithelia. Surprisingly, depletion resulted smaller more transient peripheral focal adhesions....
The lissencephaly 1 gene, LIS1 , is mutated in patients with the neurodevelopmental disease lissencephaly. Lis1 protein conserved from fungi to mammals and a key regulator of cytoplasmic dynein-1, major minus-end-directed microtubule motor many eukaryotes. only dynein known bind directly dynein’s domain, by doing so alters mechanochemistry. required for formation fully active complexes, which also contain essential cofactors: dynactin an activating adaptor. Here, we report first...
Abstract Cytoplasmic dynein-1 transports intracellular cargo towards microtubule minus ends. Dynein is autoinhibited and undergoes conformational changes to form an active complex that consists of one or two dynein dimers, the dynactin complex, activating adapter(s). The Lissencephaly 1 gene, LIS1 , genetically linked pathway from fungi mammals mutated in people with neurodevelopmental disease lissencephaly. Lis1 required for complexes form, but how it enables this unclear. Here, we present...
Cytoplasmic dynein-1 (dynein) is an essential molecular motor in eukaryotic cells. Dynein primarily exists autoinhibited Phi state and requires conformational changes to assemble with its cofactors form active transport complexes. LIS1, a key dynein regulator, enhances activation assembly. Using cryo-EM human dynein-LIS1 sample incubated ATP, we mapped the landscape of by LIS1. We discovered novel early intermediate that propose precedes our previously identified Chi state. Mutations disrupt...
Septins are GTP-binding proteins that form cytoskeleton-like filaments, which essential for many functions in eukaryotic organisms. Small molecule compounds disrupt septin filament assembly valuable tools dissecting with high temporal control. To date, forchlorfenuron (FCF) is the only compound known to affect and functions. FCF dampens dynamics of inducing formation enlarged stable polymers, but underlying mechanism action unknown. investigate how binds affects septins, we performed silico...
Intracellular transport involves the regulation of microtubule motor interactions with cargo, but underlying mechanisms are not well understood. Septins membrane- and microtubule-binding proteins that assemble into filamentous, scaffold-like structures. implicated in microtubule-dependent transport, their roles unknown. Here we describe a novel interaction between KIF17, kinesin 2 family motor, septin 9 (SEPT9). We show SEPT9 associates directly C-terminal tail KIF17 interacts preferentially...
Cytoplasmic dynein-1 transports many intracellular cargos towards microtubule minus ends. Dynein is autoinhibited and undergoes conformational changes to form an active complex, consisting of one or two dynein dimers, the dynactin complex activating adaptor(s) 1,2 . The Lissencephaly 1 gene, LIS1 , genetically linked pathway from fungi mammals mutated in patients with neurodevelopmental disease lissencephaly 3–5 Lis1 required for complexes 6–10 but how it does so unclear. Here, we present a...
Abstract The lissencephaly 1 gene, LIS1 , is mutated in patients with the neurodevelopmental disease lissencephaly. Lis1 protein conserved from fungi to mammals and a key regulator of cytoplasmic dynein-1, major minus-end-directed microtubule motor many eukaryotes. only dynein that binds directly dynein’s domain, by doing so alters mechanochemistry. required for formation fully active complexes, which also contain essential cofactors: dynactin an activating adaptor. Here, we report first...
Abscission is the terminal step of mitosis that physically separates two daughter cells. requires endocytic sorting complex required for transport (ESCRT), a molecular machinery multiple subcomplexes (ESCRT-I/II/III) promotes membrane remodeling and scission. Recruitment ESCRT-I/II complexes to midbody telophase cells initiates ESCRT-III assembly into rings, which subsequently expand helices spirals narrow down incipient site abscission. highly dynamic spatiotemporally ordered, but...
Visualization of LRRK2 filaments in 293T cells GOAL: Express GFP-LRRK2 with or without DARPin E11 and quantify the percentage presence absence MLi-2 cells.
Cytoplasmic dynein-1 (dynein) is an essential molecular motor controlled in part by autoinhibition. We recently identified a structure of partially autoinhibited dynein bound to Lis1, key regulator mutated the neurodevelopmental disease lissencephaly. This provides intermediate state activation pathway; however, other structural information needed fully explain Lis1 function activation. Here, we used cryo-EM and samples incubated with ATP for different times reveal novel conformations that...
Abstract Leucine rich repeat kinase 2 (LRRK2) is a large multidomain protein containing two catalytic domains, and GTPase, as well interactions including WD40 domain. The association of increased LRRK2 activity with both the familial sporadic forms Parkinson’s disease (PD) has led to intense interest in determining its cellular function. However, small molecule probes that can bind report on or affect are needed. Here, we identified series high-affinity LRRK2-binding designed ankyrin-repeat...
Doing scientific research can be a challenging, but creative and rewarding career. However, the challenge of doing is orders magnitude more difficult for scientists lacking access to necessary resources. Resource-scarce environments are quite common worldwide highly contingent on financial social climate one's location. Through experiences four scientists, this Perspective explores challenges associated with in disadvantaged socioeconomic circumstances. By reflecting humble beginnings these...