A5034415383- Genetics, Aging, and Longevity in Model Organisms
- Circadian rhythm and melatonin
- Spaceflight effects on biology
- Reproductive Biology and Fertility
- CRISPR and Genetic Engineering
- Photosynthetic Processes and Mechanisms
- Pluripotent Stem Cells Research
- Mitochondrial Function and Pathology
- Cellular Mechanics and Interactions
- Tissue Engineering and Regenerative Medicine
- Cell Adhesion Molecules Research
- RNA Research and Splicing
- Light effects on plants
- Neonatal Respiratory Health Research
- Neurobiology and Insect Physiology Research
- Extracellular vesicles in disease
- ATP Synthase and ATPases Research
- Muscle Physiology and Disorders
- Microtubule and mitosis dynamics
- Algal biology and biofuel production
- Plant Stress Responses and Tolerance
- Renal and related cancers
- Pharmacology and Obesity Treatment
- Congenital Anomalies and Fetal Surgery
- Spinal Fractures and Fixation Techniques
New York University
2015-2024
University of Wisconsin–Madison
2024
Indiana University School of Medicine
2023
Cancer Institute (WIA)
2011
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2003-2005
Fred Hutch Cancer Center
2002-2004
Howard Hughes Medical Institute
2002-2004
University of Arizona
1999-2000
PAR proteins distribute asymmetrically across the anterior-posterior axis of 1-cell-stage C. elegans embryo, and function to establish subsequent asymmetries. By end 4-cell stage, anteriorly localized proteins, such as PAR-3 PAR-6, redistribute outer, apical surfaces cells, whereas posteriorly PAR-1 PAR-2, inner, basolateral surfaces. Because are provided maternally, distinguishing apicobasal from earlier functions requires a method that selectively prevents activity after 1-cell stage. In...
The capability to conditionally inactivate gene function is essential for understanding the molecular basis of development. In and mRNA targeting approaches, protein products can perdure, complicating genetic analysis. Current methods selective degradation require drug treatment or take hours removal, limiting their utility in studying rapid developmental processes vivo. Here, we repurpose an endogenous system rapidly remove targeted C. elegans proteins. We show that upon expression E3...
The apicobasal polarity of epithelial cells is critical for organ morphogenesis and function, loss can promote tumorigenesis. Most form when precursor receive a polarization cue, develop distinct apical basolateral domains assemble junctions near their surface. scaffolding protein PAR-3 regulates cell polarity, but its cellular role in the transition from to polarized has not been determined vivo. Here, we use targeted protein-degradation strategy remove C. elegans embryos examine as...
Early embryos of some metazoans polarize radially to facilitate critical patterning events such as gastrulation and asymmetric cell division; however, little is known about how radial polarity established. Caenorhabditis elegans when contacts restrict the protein PAR-6 contact-free surfaces, where regulates movements. We have identified a Rho guanosine triphosphatase activating (RhoGAP), PAC-1, which mediates C. by excluding from contacted surfaces. show that PAC-1 recruited contacts, we...
Significance Cells must interact with their environment to survive. The lipids and proteins of the plasma membrane send receive signals at cell surface respond stimuli. When lipid bilayer is damaged, cells release membrane-bound extracellular vesicles repair membrane. also on communicate a distance. Here, we identify that regulate formation from membrane, providing additional tools control can be used test potential functions vesicles. Furthermore, reveal regulating asymmetric localization...
Gastrulation in C. elegans embryos involves formation of a blastocoel and the ingression surface cells into blastocoel. Mutations par-3 gene cause abnormal separations between embryonic cells, suggesting that PAR-3 protein has role formation. In normal development, PAR proteins localize to either apical or basal surfaces prior formation; we demonstrate this localization is determined by cell contacts. Cells ingress undergo an flattening associated with concentration non-muscle myosin. We...
Epithelial cells perform important roles in the formation and function of organs genesis many solid tumors. A distinguishing feature epithelial is their apicobasal polarity presence apical junctions that link together. The interacting proteins Par-6 (a PDZ CRIB domain protein) aPKC (an atypical protein kinase C) localize apically fly mammalian are for junction formation. Caenorhabditis elegans PAR-6 PKC-3/aPKC also cells, but a role these polarizing or forming has not been described. Here,...
The four-cell C. elegans embryo contains two sister cells called ABa and ABp that initially have equivalent abilities to produce ectodermal cell types. Multiple Notch-mediated interactions occur during the early divisions diversify descendants. first interaction determines pattern of types produced by ABp. second induces granddaughters become mesodermal precursors. We show T-box transcription factors TBX-37 TBX-38 are essential for induction, these expressed in ABa, but not ABp, provide...
Gastrulation movements place endodermal precursors, mesodermal precursors and primordial germ cells (PGCs) into the interior of embryo. Somatic cell gastrulation are regulated by transcription factors that also control fate, coupling identity position. By contrast, PGCs in many species transcriptionally quiescent, suggesting they might use alternative strategies. Here, we show C. elegans internalize attaching to internal cells, which undergo morphogenetic pull We enrich HMR-1/E-cadherin at...
Polarization of early embryos provides a foundation to execute essential patterning and morphogenetic events. In Caenorhabditis elegans, cell contacts polarize along their radial axis by excluding the cortical polarity protein PAR-6 from sites contact, thereby restricting contact-free surfaces. Radial polarization requires cortically enriched Rho GTPase CDC-42, which in its active form recruits through direct binding. The activating (RhoGAP) PAC-1, localizes specifically contacts, triggers...
During morphogenesis, adherens junctions (AJs) remodel to allow changes in cell shape and position while preserving adhesion. Here, we examine the function of Rho guanosine triphosphatase CDC-42 AJ formation regulation during Caenorhabditis elegans embryo elongation, a process driven by asymmetric epidermal changes. cdc-42 mutant embryos arrest elongation with ruptures. Unexpectedly, find using time-lapse fluorescence imaging that is not required for polarization or junction assembly, but...
Mitochondria harbor an independent genome, called mitochondrial DNA (mtDNA), which contains essential metabolic genes. Although mtDNA mutations occur at high frequency, they are inherited infrequently, indicating that germline mechanisms limit their accumulation. To determine how is regulated, we examined the control of quantity and quality in C. elegans primordial germ cells (PGCs). We show PGCs combine strategies to generate a low point number by segregating mitochondria into lobe-like...
The narrowest biological tubes are comprised of cells that hollow to form an intracellular lumen. Here, we examine early lumenogenesis the C. elegans excretory cell, which branches H-shaped tube spanning length worm. Using genetically paralyzed embryos freeze movement, describe lumen initiation and branching for first time using time-lapse fluorescence microscopy. We show cell forms through a plasma membrane invasion mechanism when nascent grows from into cytoplasm. subsequently extends...