A5004435983- Erythrocyte Function and Pathophysiology
- Blood properties and coagulation
- Ion channel regulation and function
- Cellular Mechanics and Interactions
- DNA Repair Mechanisms
- Herpesvirus Infections and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Poxvirus research and outbreaks
- CRISPR and Genetic Engineering
- Cytomegalovirus and herpesvirus research
- Virus-based gene therapy research
- Carcinogens and Genotoxicity Assessment
- Bacteriophages and microbial interactions
- Glycosylation and Glycoproteins Research
- Genomics and Chromatin Dynamics
- Chemical and Physical Studies
- 3D Printing in Biomedical Research
- DNA and Nucleic Acid Chemistry
- Genetic factors in colorectal cancer
- Immune Cell Function and Interaction
- Blood groups and transfusion
- Neurogenesis and neuroplasticity mechanisms
- Gender, Feminism, and Media
- Genetic Syndromes and Imprinting
- Microfluidic and Bio-sensing Technologies
University of California, Irvine
2020-2025
University of Leeds
2018-2024
UC Irvine Health
2021
Cornell University
1990-2000
Cancer Research UK
1999-2000
University of Cambridge
1997
The Honourable Society of Lincoln's Inn
1996
Harvard University
1996
Children's Research Hospital
1996
The University of Texas MD Anderson Cancer Center
1989
Keratinocytes, the predominant cell type of epidermis, migrate to reinstate epithelial barrier during wound healing. Mechanical cues are known regulate keratinocyte re-epithelialization and healing; however, underlying molecular transducers biophysical mechanisms remain elusive. Here, we show through molecular, cellular, organismal studies that mechanically activated ion channel PIEZO1 regulates migration Epidermal-specific Piezo1 knockout mice exhibited faster closure while gain-of-function...
IL-2 potentiates both growth and cytotoxic function of T lymphocytes NK cells. Resting peripheral blood cells can respond directly to rIL-2, without requirement for accessory or cofactors, enhanced cytotoxicity be measured within a few hours after exposure this lymphokine. In study, we describe an activation antigen, Leu-23, that is rapidly induced phosphorylated stimulation subset low buoyant density lymphocytes. Previously, it has been uncertain whether all only are responsive IL-2. Since...
The mechanosensitive Piezo1 channel has important roles in vascular physiology and disease. Yoda1 is a small-molecule agonist, but the pharmacology of these channels otherwise limited.Yoda1 analogues were generated by synthetic chemistry. Intracellular Ca2+ Tl+ measurements made HEK 293 or CHO cell lines overexpressing subunits HUVECs, which natively express Piezo1. Isometric tension recordings from rings mouse thoracic aorta.Modification pyrazine ring yielded an analogue, lacked agonist...
Piezo1 is a mechanosensitive cation channel with widespread physiological importance; however, its role in the heart poorly understood. Cardiac fibroblasts help preserve myocardial integrity and play key regulating repair remodeling following stress or injury. Here we investigated expression function cultured human mouse cardiac fibroblasts. RT-PCR experiments confirmed that mRNA expressed at levels similar to those endothelial cells. The results of Fura-2 intracellular Ca2+ assay validated...
Piezo1 forms mechanically activated nonselective cation channels that contribute to endothelial response fluid flow. Here we reveal an important role in the control of capillary density. Conditional cell–specific deletion adult mice depressed physical performance. Muscle microvascular cell apoptosis and rarefaction were evident sufficient account for effect on There was selective upregulation thrombospondin-2 (TSP2), inducer apoptosis, with no TSP1, a related player muscle physiology. TSP2...
The collective migration of keratinocytes during wound healing requires both the generation and transmission mechanical forces for individual cellular locomotion coordination movement across cells. Leader cells along edge transmit biochemical cues to ensuing follower cells, ensuring their coordinated direction multiple Despite observed importance in leader cell formation controlling directionality migration, underlying biophysical mechanisms remain elusive. mechanically-activated ion channel...
The human XPG endonuclease cuts on the 3' side of a DNA lesion during nucleotide excision repair. Mutations in can lead to disorders xeroderma pigmentosum (XP) and Cockayne syndrome. shares sequence similarities two regions with family structure-specific nucleases exonucleases. To begin defining its catalytic mechanism, we changed highly conserved residues determined effects activity isolated XPG, function open complex formation dual incision reconstituted purified proteins, ability restore...
Vaccinia virus mutants ts2 and ts25, members of the same complementation group, exhibit a temperature-dependent arrest at stage viral DNA replication. The lesions responsible for mutant phenotypes have been localized to far left region HindIII B genomic fragment by marker rescue studies. Hybrid selection analyses established that fragments positive represented first open reading frame encoded 30-kilodalton protein. gene is expressed early after infection as rightwardly transcribed...
Mechanical forces and tissue mechanics influence the morphology of developing brain, but underlying molecular mechanisms have been elusive. Here, we examine role mechanotransduction in brain development by focusing on Piezo1, a mechanically activated ion channel. We find that Piezo1 deletion results thinner neuroepithelial layer, disrupts pseudostratification, reduces neurogenesis E10.5 mouse embryos. Proliferation differentiation knockout (KO) neural stem cells (NSCs) isolated from embryos...
PIEZO1 is a subunit of mechanically-activated, nonselective cation channels. Gain-of-function mutations are associated with dehydrated hereditary stomatocytosis (DHS), type anaemia, due to abnormal red blood cell function. Here, we hypothesised additional effects on the heart. Consistent this hypothesis, mice engineered contain M2241R mutation in mimic DHS had increased cardiac mass and interventricular septum thickness at 8-12 weeks age, without altered contractility. Myocyte size was...
Mismatch repair proteins act during double-strand break (DSBR) to correct mismatches in heteroduplex DNA, suppress recombination between divergent sequences, and promote removal of nonhomologous DNA at DSB ends. We investigated yeast Msh2p association with intermediates vivo using chromatin immunoprecipitation. During DSBR involving ends, localized strongly recipient donor sequences. Localization required Msh3p was greatly reduced rad50Δ strains. Minimal localization observed fully...
The Leu-19 (NKH-1) antigen is expressed on human peripheral blood NK cells and a subset of cytotoxic T lymphocytes that kill "NK-sensitive" tumor cell targets without major histocompatibility complex restriction. In the present study, we demonstrate also most interleukin 2 (IL 2) dependent lines clones have been maintained in long term culture. an antigen-specific, class I directed lymphocyte line was approximately 200,000 to 220,000 dalton protein, similar protein natural killer KG1a,...
The vaccinia virus D5 gene encodes a 90-kDa protein that is transiently expressed at early times after infection. Temperature-sensitive mutants with lesions in the exhibit fast-stop DNA- phenotype and are also impaired homologous recombination. Here we report overexpression of within context infection its purification to apparent homogeneity. purified has an intrinsic nucleoside triphosphatase activity which independent of, not stimulated by, any common nucleic acid cofactors. All eight...
We have identified a gene encoded by vaccinia virus which is essential for DNA replication. The gene, located in the HindIII D fragment of viral genome, transcribed early after infection into two transcripts 3.0 and 3.7 kilobases share 3' terminus. lesions three temperature-sensitive replication mutants with defects this been localized marker rescue progressively smaller fragments. determined hybrid selection that encodes an 82-kilodalton protein. An antibody has prepared against polypeptide...
Monoclonal antibody (mAb) anti-L25 identifies an antigen on the surface of human lymphocytes. This mAb immunoprecipitated three distinct polypeptides Mr 150,000, 85,000, and 75,000 from Nonidet P-40 lysates radioiodinated The were found under both nonreducing reducing conditions. An additional polypeptide 130,000 was detected in immuno-precipitates when cells lysed with CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate). Epitope localization experiments indicated that 150,000...
The mechanically-activated ion channel PIEZO1 is critical to numerous physiological processes, and activated by diverse mechanical cues. gated membrane tension has been found be mobile in the plasma membrane. We employed single particle tracking (SPT) of endogenous, tdTomato-tagged using Total Internal Reflection Fluorescence Microscopy live cells. Application SPT unveiled a surprising heterogeneity diffusing subpopulations, which we labeled "mobile" "immobile". sorted these trajectories...