A5017303352- Genetics, Aging, and Longevity in Model Organisms
- Invertebrate Immune Response Mechanisms
- Ubiquitin and proteasome pathways
- Neurobiology and Insect Physiology Research
- Hippo pathway signaling and YAP/TAZ
- Circadian rhythm and melatonin
- Developmental Biology and Gene Regulation
- Photosynthetic Processes and Mechanisms
- Phagocytosis and Immune Regulation
- 14-3-3 protein interactions
- Microtubule and mitosis dynamics
- Endoplasmic Reticulum Stress and Disease
- Epigenetics and DNA Methylation
- Autophagy in Disease and Therapy
- Protein Kinase Regulation and GTPase Signaling
- Viral Infections and Vectors
- Mosquito-borne diseases and control
- Heat shock proteins research
- Mitochondrial Function and Pathology
- Cellular Mechanics and Interactions
- Silkworms and Sericulture Research
- Protein Tyrosine Phosphatases
- Pluripotent Stem Cells Research
University of Wisconsin–Milwaukee
2020-2024
Columbia University
2004-2020
Columbia University Irving Medical Center
2006-2017
Institute of Molecular Biology and Biophysics
2012
Howard Hughes Medical Institute
2012
Developing tissues that contain mutant or compromised cells present risks to animal health. Accordingly, the appearance of a population suboptimal in tissue elicits cellular interactions prevent their contribution adult. Here we report this quality control process, cell competition, uses specific components evolutionarily ancient and conserved innate immune system eliminate Drosophila perceived as unfit. We find Toll-related receptors (TRRs) cytokine Spätzle (Spz) lead NFκB-dependent...
The conserved E3 ubiquitin ligase component named SEL-10 in Caenorhabditis elegans and Fbw7 mammals targets substrates for ubiquitin-mediated degradation through a high-affinity binding site called Cdc4 phosphodegron (CPD). As many known of are oncoproteins, the identification new may offer insight into cancer biology as well aspects proteome regulation. Here, we evaluated whether presence an evolutionarily CPD would be feasible complement to proteomics-based approaches identifying potential...
Raf protein kinases act as Ras-GTP sensing components of the ERK signal transduction pathway in animal cells, influencing cell proliferation, differentiation, and survival. In humans, somatic germline mutations genes
Activation of a canonical EGFR-Ras-Raf-ERK cascade initiates patterning multipotent Vulval Precursor Cells (VPCs) C. elegans. We previously showed that this pathway includes negative-feedback component in which MPK-1/ERK activity targets the upstream kinase LIN-45/Raf for degradation by SEL-10/FBXW7 E3 ubiquitin ligase. This regulation requires Cdc4 phosphodegron (CPD) LIN-45 is conserved BRAF. Here, we identify and characterize minimal degron encompasses CPD sufficient SEL-10-mediated,...
The process of apoptosis in epithelia involves activation caspases, delamination cells, and degradation cellular components. Corpses debris are then rapidly cleared from the tissue by phagocytic blood cells. In studies Drosophila TNF, Eiger (Egr) cell death wing imaginal discs, epithelial primordia fly wings, we noticed that dying cells appeared to transiently accumulate egr3 mutant raising possibility their engulfment hemocytes was impaired. Further investigation revealed lymph glands...
Signaling by the kinase cascade composed of Raf, MEK, and ERK is critical for animal development often inappropriately activated in human malignancies. We sought to identify factors that control signaling mediated Caenorhabditis elegans Raf ortholog LIN-45. A genetic screen showed degradation LIN-45 required E3/E4 ubiquitin ligase UFD-2. Both UFD-2 its partner, ATP-dependent segregase CDC-48, were developmental regulation protein abundance. acted same pathway as E3 SCFSEL-10 decrease...
Abstract Raf protein kinases act as Ras-GTP sensing components of the ERK signal transduction pathway in animal cells, influencing cell proliferation, differentiation, and survival. In humans, somatic germline mutations genes BRAF RAF1 are associated with malignancies developmental disorders. Recent studies shed light on structure activated Raf, a heterotetramer consisting 14-3-3 dimers, raised possibility that C-terminal distal tail segment (DTS) regulates activation. We investigated role...
Fibroblast Growth Factors (FGFs) and their receptors (FGFRs) comprise a cell signaling module that can stimulate number of downstream pathways regulate animal development homeostatic functions. Among these is the Ras GTPase kinases Raf, MEK, ERK. In Caenorhabditis elegans, FGFR ortholog EGL-15 its intracellular adaptor SEM-5/GRB2 are required in sex myoblast (SM) for migration during development, hypodermis (Hyp7) fluid homeostasis. Cell-specific differences were suggested by phenotypes...
Numerous factors have been implicated in the cell-cell interactions that lead to elimination of cells via cell competition, a context-dependent process selection somatic tissues is based on comparisons cellular fitness. Here, we use series genetic tests Drosophila explore relative contribution pleiotropic cytokine tumor necrosis factor α (TNFα) Myc-mediated competition (also known as Myc supercompetition or competition). We find sole TNF, Eiger (Egr), its receptor Grindelwald (Grnd/TNF...
Abstract The process of apoptosis in epithelia involves activation caspases, delamination cells, and degradation cellular components. Corpses debris are then rapidly cleared from the tissue by phagocytic blood cells. In studies Drosophila TNF, Eiger (Egr) cell death wing imaginal discs, epithelial primordia fly wings, we noticed that dying cells persisted longer egr 3 mutant discs than wild type raising possibility their engulfment hemocytes was impaired. Further investigation revealed lymph...
Abstract Signaling by the kinase cascade comprised of Raf, MEK, and ERK is critical for animal development; moreover, its inappropriate activation commonly found in human malignancies. In a genetic screen factors that control signaling Caenorhabditis elegans Raf ortholog LIN-45, we it negatively regulated E3/E4 ubiquitin ligase UFD-2. Both UFD-2 partner, ATP-dependent unfoldase CDC-48, were required degradation LIN-45 protein. Our structure-function studies showed disruption domains mediate...
Abstract Numerous factors have been implicated in the cell-cell interactions that lead to elimination of cells via cell competition, a context-dependent process selection somatic tissues is based on comparisons cellular fitness. Here we use series genetic tests Drosophila explore relative contribution pleiotropic cytokine Tumor Necrosis Factor ⍺ (TNF⍺) Myc-mediated competition (also known as Myc super-competition or competition). We find sole TNF, Eiger (Egr), its receptor Grindelwald...