A5089633537- Cell Adhesion Molecules Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cellular Mechanics and Interactions
- Immune cells in cancer
- Immune Response and Inflammation
- Protease and Inhibitor Mechanisms
- interferon and immune responses
- Zebrafish Biomedical Research Applications
- Pluripotent Stem Cells Research
- Calpain Protease Function and Regulation
- Signaling Pathways in Disease
- Ubiquitin and proteasome pathways
- Erythrocyte Function and Pathophysiology
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Platelet Disorders and Treatments
- 3D Printing in Biomedical Research
- Cellular transport and secretion
- Blood disorders and treatments
- Protein Kinase Regulation and GTPase Signaling
- T-cell and B-cell Immunology
- Phagocytosis and Immune Regulation
- Micro and Nano Robotics
- Neonatal Respiratory Health Research
- Cancer Research and Treatments
University of Wisconsin–Madison
2015-2025
University of Wisconsin Carbone Cancer Center
2023-2025
Ramathibodi Hospital
2020
Mahidol University
2020
University of Cape Coast
2020
Cyclin G2, together with cyclin G1 and I, defines a novel family expressed in terminally differentiated tissues including brain muscle. G2 expression is up-regulated as cells undergo cell cycle arrest or apoptosis response to inhibitory stimuli independent of p53 (Horne, M., Donaldson, K., Goolsby, G., Tran, D., Mulheisen, Hell, J. Wahl, A. (1997) <i>J. Biol. Chem.</i> 272, 12650–12661). We tested the hypothesis that may be negative regulator progression found ectopic induces formation...
The coordinated and dynamic regulation of adhesions is required for cell migration. We demonstrated previously that limited proteolysis talin1 by the calcium-dependent protease calpain 2 plays a critical role in adhesion disassembly fibroblasts (Franco, S. J., Rodgers, M. A., Perrin, B. Han, Bennin, D. Critchley, R., Huttenlocher, A. (2004) Nat. Cell Biol. 6, 977-983). However, little known about contribution other substrates to dynamics. now provide evidence 2-mediated focal kinase (FAK)...
Abstract Direct visualization and characterization of Cxcr2 signaling as a mediator systemic neutrophil reaction to local infection. Neutrophils are the first line defense against tissue damage rapidly mobilized sites bacterial However, signals that regulate recruitment not well defined. Here, using photolabel-enabled fate mapping in zebrafish larvae, we show localized otic infection with Pseudomonas aeruginosa induces activation mobilization neutrophils from CHT through signaling. We have...
Mammalian cDNA expression cloning was used to identify novel regulators of integrin-mediated cell-substratum adhesions. Using a focal adhesion morphology screen, we identified with homology receptor for activated protein kinase C (RACK1) that induced loss central adhesions and stress fibers in CHO-K1 cells. The C-terminal truncated form RACK1 had one the putative binding sites but lacked region proposed bind β integrin cytoplasmic domain tyrosine Src. To investigate role during cell...
The dynamic turnover of integrin-mediated adhesions is important for cell migration. Paxillin an adaptor protein that localizes to focal and has been implicated in motility. We previously reported calpain-mediated proteolysis talin1 adhesion kinase mediates disassembly motile cells. To determine whether paxillin regulates dynamics motility, we mapped the preferred calpain proteolytic site paxillin. cleavage between LD1 LD2 motifs generates a C-terminal fragment similar size alternative...
Abstract Neutrophilic inflammation is a hallmark of many monogenic autoinflammatory diseases; pathomechanisms that regulate extravasation damaging immune cells into surrounding tissues are poorly understood. Here we identified three unrelated boys with perinatal-onset neutrophilic cutaneous small vessel vasculitis and systemic inflammation. Two patients developed liver fibrosis in their first year life. Next-generation sequencing two de novo truncating variants the Src-family tyrosine...
ABSTRACT Neutrophil-directed motility is necessary for host defense, but its dysregulation can also cause collateral tissue damage. Actinopathies are monogenic disorders that affect the actin cytoskeleton and lead to immune dysregulation. Deficiency in ARPC1B, a component of Arp2/3 complex, results vascular neutrophilic inflammation; however, mechanism remains unclear. Here, we generated human induced pluripotent stem cell (iPSC)-derived neutrophils (denoted iNeutrophils) deficient ARPC1B...
T cell-APC contact initiates cell activation and is maintained by the integrin LFA-1. Talin1, an LFA-1 regulator, localizes to immune synapse (IS) with unknown roles in activation. In this study, we show that talin1-deficient cells have defects contact-dependent stopping proliferation. Although did not form stable interactions APCs, transient contacts were sufficient induce signaling. contrast prior models, polarized cells, but vinculin F-actin polarization at IS was impaired. These results...
Neutrophil migration is essential for inflammatory responses to kill pathogens; however, excessive neutrophilic inflammation also leads tissue injury and adverse effects. To discover novel therapeutic targets that modulate neutrophil migration, we performed a neutrophil-specific microRNA (miRNA) overexpression screen in zebrafish identified 8 miRNAs as potent suppressors of migration. Among those,
Human induced pluripotent stem cells (hiPSCs) can serve as a versatile and scalable source of neutrophils for biomedical research transfusion therapies. Here we describe rapid efficient serum- xenogen-free protocol neutrophil generation, which is based on direct hematoendothelial programming hiPSCs using ETV2-modified mRNA. Culture ETV2-induced progenitors in the presence GM-CSF, FGF2, UM171 led to continuous production generous amounts CD34+CD33+ myeloid could be harvested every 8–10 days...
Neutrophil recruitment to tissue damage is essential for host defense but can also impede repair. The cues that differentially regulate neutrophil responses and infection remain unclear. Here, we report the paracrine factor myeloid-derived growth (MYDGF) induced by regulates motility damaged, not infected, tissues in zebrafish larvae. Depletion of MYDGF impairs wound healing, this phenotype rescued depleting neutrophils. Live imaging photoconversion reveal impaired reverse migration...
Neutrophils are rapidly recruited to sites of infection and critical for pathogen clearance. Therapeutic use primary neutrophils has been limited, as they have a short lifespan not amenable genetic manipulation. Human induced pluripotent stem cells (iPSCs) can provide robust source infusion genetically tractable. However, current work indicated that dampened intracellular signaling limits iPSC-derived neutrophil (iNeutrophil) cellular activation antimicrobial response. Here, we show protein...
Neutrophils are critical for host defense against fungi. However, the short life span and lack of genetic tractability primary human neutrophils has limited in vitro analysis neutrophil-fungal interactions. Human induced pluripotent stem cell (iPSC)-derived (iNeutrophils) provide a genetically tractable system to study responses neutrophils. Here, we show that deletion transcription factor GATA1 from iPSCs results iNeutrophils with improved antifungal activity Aspergillus fumigatus....
Abstract Leukocytes forge paths through interstitial spaces by exerting forces to overcome confining mechanical pressures provided surrounding cells. While such cues regulate leukocyte motility, engineering an in vitro system that models the deformable cellular environment encountered vivo has been challenging. Here, microchannels are constructed with a liquid‐liquid interface exerts similar cells tissues, and thus, is cell‐generated forces. Consequently, balance between migratory...
Cell polarization is necessary for directed migration and leukocyte recruitment to inflamed tissues. Recent progress has been made in defining the molecular mechanisms that regulate chemoattractant-induced cell polarity during chemotaxis, including contribution of phosphoinositide 3-kinase (PI3K)-dependent phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P(3)] synthesis at leading edge. However, less known about composition rear how uropod functions motility. Here, we demonstrate...
Epidermal hyperproliferation and inflammation are hallmarks of the human condition psoriasis. Here, we report that a zebrafish line with mutation in cargo adaptor protein Clint1 exhibits psoriasis-like phenotypes including epithelial leukocyte infiltration. is an ENTH domain-containing binds SNARE proteins functions vesicle trafficking; however, its vivo function animal models has not been reported to date. The clint1 mutants exhibit chronic characterized by increased Interleukin 1β...
Abstract Introduction Rheumatoid arthritis is an autoimmune characterized by joint destruction. Anti-citrullinated protein antibodies are pathologic in rheumatoid arthritis, but the role of citrullinated proteins themselves much less clear. Citrullination conversion arginine residues a to citrulline. In inflamed there increased citrullination. Several including collagen type II, fibrinogen, and fibronectin. Fibronectin thought mediate adhesion joint-invading synovial fibroblasts cartilage...
Neutrophils are primary phagocytes of the innate immune system that generate reactive oxygen species (ROS) and mediate host defense. Deficient phagocyte NADPH oxidase (PHOX) function leads to chronic granulomatous disease (CGD) is characterized by invasive infections, including those generally non-pathogenic fungus Aspergillus nidulans The role neutrophil ROS in this specific host-pathogen interaction remains unclear. Here, we exploit optical transparency zebrafish image effects on fungal...
Growth factor stimulation induces the formation of dynamic actin structures known as dorsal ruffles. Mammalian actin-binding protein-1 (mAbp1) is an protein that has been implicated in regulating clathrin-mediated endocytosis; however, a role for mAbp1 dynamics growth factor-induced actin-based not defined. Here we show localizes to ruffles and necessary platelet-derived (PDGF)-mediated ruffle formation. Despite their structural similarity, find cortactin have nonredundant functions...
Pombe Cdc15 homology (PCH) family members have emerged as important regulators of membrane-cytoskeletal interactions. Here we show that PSTPIP1, a PCH member expressed in hematopoietic cells, regulates the motility neutrophil-like cells and is novel component leukocyte uropod where it colocalizes with other components, such type I PIPKIgamma. Furthermore, PSTPIP1 association regulator endocytosis, dynamin 2, expression impairs transferrin uptake endocytosis. We also localizes at rear...
Factor for adipocyte differentiation 24 (fad24) is a novel gene that has been implicated in and DNA replication. In screen zebrafish mutants have an abnormal tissue distribution of neutrophils, we identified insertional allele fad24, fad24hi1019. Homozygous fad24hi1019 larvae exhibit muscle degeneration accompanied by leukocyte infiltration. Muscle was extensive included apoptosis disorganized, poorly striated fibers. Blocking using pan-caspase inhibitors resulted decreased neutrophil...