A5090075416- Genetics, Aging, and Longevity in Model Organisms
- Circadian rhythm and melatonin
- Endoplasmic Reticulum Stress and Disease
- CRISPR and Genetic Engineering
- Genomics, phytochemicals, and oxidative stress
- Lipid Membrane Structure and Behavior
- Neuroendocrine regulation and behavior
- Tryptophan and brain disorders
- Biochemical and Molecular Research
- Gut microbiota and health
- Insect symbiosis and bacterial influences
- Sexual function and dysfunction studies
- Urinary Bladder and Prostate Research
- Pelvic floor disorders treatments
- Spectroscopy and Quantum Chemical Studies
- Polymer Surface Interaction Studies
- Glycosylation and Glycoproteins Research
- Genital Health and Disease
- Photosynthetic Processes and Mechanisms
- Sexuality, Behavior, and Technology
- Prostate Cancer Diagnosis and Treatment
- Aging and Gerontology Research
- Selenium in Biological Systems
- Anorectal Disease Treatments and Outcomes
- Medicinal Plants and Neuroprotection
Harvard University
2002-2025
Boston Children's Hospital
2019-2025
Massachusetts Institute of Technology
2010-2023
Boston University
2023
Columbia University Irving Medical Center
2017-2018
James A. Haley Veterans' Hospital
2011
Florida College
2011
University of South Florida
2011
Cleveland Clinic Florida
2009-2010
Howard Hughes Medical Institute
2009
A genetic screen for Caenorhabditis elegans mutants with enhanced susceptibility to killing by Pseudomonas aeruginosa led the identification of two genes required pathogen resistance: sek-1 , which encodes a mitogen-activated protein (MAP) kinase kinase, and nsy-1 MAP kinase. RNA interference assays biochemical analysis established that p38 ortholog, pmk-1 functions as downstream defense. These data suggest this signaling cassette represents an ancient feature innate immune responses in...
The PMK-1 p38 mitogen-activated protein kinase pathway and the DAF-2–DAF-16 insulin signaling control Caenorhabditis elegans intestinal innate immunity. pmk-1 loss-of-function mutants have enhanced sensitivity to pathogens, while daf-2 resistance pathogens that requires upregulation of DAF-16 transcription factor. We used genetic analysis show pathogen also PMK-1. However, genome-wide microarray indicated there was essentially no overlap between genes positively regulated by DAF-16,...
Endosomal trafficking protein TBC ‐2 modulates stress resistance and lifespan through DAF ‐16‐dependent independent mechanisms ,
The nematode Caenorhabditis elegans responds to pathogenic bacteria with conserved innate immune responses and pathogen avoidance behaviors. We investigated natural variation in C. resistance infection. With the use of quantitative genetic analysis, we determined that susceptibility difference between laboratory wild-type strain N2 wild isolate CB4856 is caused by a polymorphism npr-1 gene, which encodes homolog mammalian neuropeptide Y receptor. show mechanism NPR-1-mediated through...
The p38 mitogen-activated protein kinase pathway regulates innate immune responses in evolutionarily diverse species. We have previously shown that the Caenorhabditis elegans kinase, PMK-1, functions an response mediates resistance to a variety of microbial pathogens. Here, we show tir-1, gene encoding highly conserved Toll/IL-1 (TIR) domain protein, is also required for C. RNA interference inactivation tir-1 resulted enhanced susceptibility killing by pathogens and correspondingly...
The antibiotic fosfomycin inhibits bacterial cell wall biosynthesis by inactivation of UDP-GlcNAc enolpyruvyl tranferase (MurA). Prior work has established that Cys115 Escherichia coli and Enterobacter cloacae MurA is the active site nucleophile alkylated implicated this residue in formation a covalent phospholactyl-enzyme adduct derived from substrate, phosphoenolpyruvate (PEP). On basis sequencing information putative homolog Mycobacterium tuberculosis, we generated C115D mutant E. was...
The p38 and JNK classes of mitogen-activated protein kinases (MAPKs) have evolutionarily conserved roles in the control cellular responses to microbial abiotic stresses. mechanisms by which crosstalk between distinct c-Jun N-terminal kinase (JNK) MAPK pathways occurs with resultant integration signaling information been difficult establish, particularly context whole organism physiology. In Caenorhabditis elegans a PMK-1 pathway is required for resistance bacterial infection, KGB-1 JNK-like...
Innate immunity in Caenorhabditis elegans requires a conserved PMK-1 p38 mitogen-activated protein kinase (MAPK) pathway that regulates the basal and pathogen-induced expression of immune effectors. The mechanisms by which MAPK transcriptional activation C. response have not been identified. Furthermore, mammalian systems genetic analysis physiological targets has limited. Here, we show ATF-7, member cyclic AMP–responsive element binding (CREB)/activating transcription factor (ATF) family...
The decline in immune function with aging, known as immunosenescence, has been implicated evolutionarily diverse species, but the underlying molecular mechanisms are not understood. During aging Caenorhabditis elegans, intestinal tissue deterioration and increased proliferation of bacteria observed, how innate immunity changes during C. elegans defined. Here we show that exhibits susceptibility to bacterial infection age, establish is associated a activity conserved PMK-1 p38...
A polycrystalline phospholipid monolayer self-assembled at the surface of an air microbubble in aqueous solution represents a novel material structure: essence, solid shell wax with micrometer-scale dimensions and thickness only single molecule. Micropipet manipulation these microparticles revealed dependence mechanical properties lipid shells, specifically, yield shear viscosity, on composition, grain microstructure, thermal processing material, particular cooling rate shells from melt....
Innate immunity is an ancient defense system used by both vertebrates and invertebrates. Previously characterized innate immune responses in plants animals are triggered detection of pathogens using specific receptors, which typically use a leucine-rich repeat (LRR) domain to bind molecular patterns associated with infection. The nematode Caenorhabditis elegans uses pathways conserved vertebrates; however, the mechanism C. detects unknown. We screened all LRR-containing transmembrane...
The nematode Caenorhabditis elegans has emerged as a genetically tractable animal host in which to study evolutionarily conserved mechanisms of innate immune signaling. We previously showed that the PMK-1 p38 mitogen-activated protein kinase (MAPK) pathway regulates immunity C. through phosphorylation CREB/ATF bZIP transcription factor, ATF-7. Here, we have undertaken genomic analysis transcriptional response infection by Pseudomonas aeruginosa, combining genome-wide expression RNA-seq with...
Animal behavior is directed by the integration of sensory information from internal states and environment. Neuroendocrine regulation diverse behaviors Caenorhabditis elegans under control DAF-7/TGF-β ligand that secreted neurons. Here, we show C. males exhibit an altered, male-specific expression pattern daf-7 in ASJ neuron pair with onset reproductive maturity, which functions to promote mate-searching behavior. Molecular genetic analysis switch-like reveals a hierarchy among multiple...
Phospholipid monolayers at the water−air interface have been used extensively as models approximating one-half of biological bilayer membrane and are particular interest stabilizers microbubbles emulsions. Interfacial tension is an important measure adsorption monolayer formation, but for macroscopic interfaces, equilibrium conditions difficult if not impossible to reach, especially over wide range temperatures necessary study homologous series lipids such phosphatidylcholines (C12−C18). By...