A5037187560- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Ubiquitin and proteasome pathways
- IL-33, ST2, and ILC Pathways
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer-related Molecular Pathways
- Gut microbiota and health
- Microtubule and mitosis dynamics
- CRISPR and Genetic Engineering
- Wnt/β-catenin signaling in development and cancer
- RNA Interference and Gene Delivery
- Enzyme Catalysis and Immobilization
- Forensic and Genetic Research
- Clostridium difficile and Clostridium perfringens research
- Autophagy in Disease and Therapy
- Cancer-related gene regulation
- RNA and protein synthesis mechanisms
- Hematopoietic Stem Cell Transplantation
- Viral Infectious Diseases and Gene Expression in Insects
- Immune Response and Inflammation
- Protein Degradation and Inhibitors
- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
Washington University in St. Louis
2022-2025
St. Jude Children's Research Hospital
2009-2024
University of Basel
2018-2023
Conventional dendritic cells (cDC) are antigen-presenting comprising cDC1 and cDC2, responsible for priming naive CD8
Ubiquitination by HECT E3 enzymes regulates myriad processes, including tumor suppression, transcription, protein trafficking, and degradation. E3s use a two-step mechanism to ligate ubiquitin target proteins. The first step is guided interactions between the catalytic domain E2∼ubiquitin intermediate, which promote formation of transient, thioester-bonded HECT∼ubiquitin intermediate. Here we report that second ligation mediated distinct architecture established both its covalently linked...
Significance The anaphase-promoting complex/cyclosome (APC) is a multisubunit RING E3 ubiquitin (Ub) ligase that regulates mitosis, meiosis, and numerous facets of neurobiology by targeting key regulatory proteins for Ub-mediated degradation. Despite great importance, it remains unclear how APC, or most the other 600 E3s in humans, targets Ub to lysines disordered substrates. Here, we report structural molecular basis substrate ubiquitination APC its partner E2, UBCH10. UBCH10 recruited...
Plasmacytoid dendritic cells (pDCs) have been shown to play an important role during immune responses, ranging from initial viral control through the production of type I interferons antigen presentation. However, recent studies uncovered unexpected heterogeneity among pDCs. We identified a previously uncharacterized subset, referred as pDC-like cells, that not only resembles pDCs but also shares conventional DC (cDC) features. show this subset is circulating precursor distinct common...
The gut microbiota and tumor-associated macrophages (TAMs) affect tumor responses to anti–programmed cell death protein 1 (PD-1) immune checkpoint blockade. Reprogramming TAM by either blocking or deleting the macrophage receptor triggering on myeloid cells 2 (TREM2) attenuates growth, lack of functional TREM2 enhances elimination anti–PD-1. Here, we found that anti–PD-1 treatment combined with deficiency in mice induces proinflammatory programs intestinal a concomitant expansion...
Recent studies have characterized various mouse antigen-presenting cells (APCs) expressing the lymphoid-lineage transcription factor RORγt (Retinoid-related orphan receptor gamma t), which exhibit distinct phenotypic features and are implicated in induction of peripheral regulatory T (Tregs) immune tolerance to microbiota self-antigens. These APCs encompass Janus Thetis cell subsets, some express AutoImmune REgulator (AIRE). + MHCII type 3 innate lymphoid (ILC3) also been instruction...
The soluble flavoprotein oleate hydratase (OhyA) hydrates the 9-cis double bond of unsaturated fatty acids. OhyA substrates are embedded in membrane bilayers; must remove acid from bilayer and enclose it active site. Here, we show that positively charged helix-turn-helix motif carboxy terminus (CTD) is responsible for interacting with negatively phosphatidylglycerol (PG) bilayer. Super-resolution microscopy Staphylococcus aureus cells expressing green fluorescent protein fused to or CTD...
Group 2 innate lymphoid cells (ILC2) are counterparts of T helper (Th2) that maintain tissue homeostasis and respond to injuries through rapid interleukin (IL)-5 IL-13 secretion. ILC2s depend on availability arginine branched-chain amino acids for sustaining cellular fitness, proliferation, cytokine secretion in both steady state upon activation. However, the contribution acid transporters ILC2 functions is not known. Here, we found selectively express Slc7a8 , encoding a transporter large...
Here, we explore the relationship between dietary fibers, colonic epithelium major histocompatibility complex class II (MHC-II) expression, and immune cell interactions in regulating susceptibility to Clostridioides difficile infection (CDI). We find that a low-fiber diet increases MHC-II expression epithelium, which, turn, worsens CDI by promoting development of pathogenic CD4+ intraepithelial lymphocytes (IELs). The influence fibers on is mediated its metabolic product, acetate, receptor,...
Members of the Wnt family lipoglycoproteins initiate signaling by binding to Frizzled (Fz) receptors, and signal is then relayed Disheveled (Dvl). The Dvl PDZ domain known interact directly with a peptide derived from KTXXXW motif Fz7, which conserved in all Fz subtypes. We found that an extended region spanning on both its N-terminal C-terminal sides dramatically influences affinity peptides Fz7 for PDZ. An alanine scanning study identified specific residues external are important...
Abstract Testis-restricted melanoma antigen (MAGE) proteins are frequently hijacked in cancer and play a critical role tumorigenesis. MAGEs assemble with E3 ubiquitin ligases function as substrate adaptors that direct the ubiquitination of novel targets, including key tumor suppressors. However, how recognize their targets is unknown has impeded development MAGE-directed therapeutics. Here, we report structural basis for recognition by MAGE ligases. Biochemical analysis degron motif...
Microglia are thought to originate exclusively from primitive macrophage progenitors in the yolk sac (YS) and persist throughout life without much contribution definitive hematopoiesis. Here, using lineage tracing, pharmacological manipulation, RNA-sequencing, we elucidated presence characteristics of monocyte-derived macrophages (MDMs) brain parenchyma at baseline during microglia repopulation, defined core transcriptional signatures brain-engrafted MDMs. Lineage tracing mouse models...
Punchihewa C, Ferreira AM, Cassell R, Rodrigues P, Fujii N. (2009) Protein Sci 18:994–1002. Due to a typographical error, the affiliation for Robert in above-titled article was not published correctly. All affiliations are presented here as they should have appeared.
Abstract Myeloid cell types including conventional dendritic cells (cDCs) and macrophages are key responders to innate stimuli at epithelial barriers. They equipped with receptors sense danger signals pathogens, becoming the first line of immune defense thereby maintaining homeostasis. The expression selected transcription factors was shown be essential for development these myeloid subsets Batf3, Notch2, Irf4, Irf8 among others. We performed single-cell RNA analysis across eight different...
Lentiviral (LV) vector-based gene therapy is gaining popularity for treating a wide range of diseases. Various LV vectors are being developed transducing cells in cellular at St. Jude. Some produced using stable 293T packaging cell lines, which includes gag-pol-rev-tat and virus-glycoprotein. Transactivating factor (transactivator transcription [Tat]) regulatory protein that drastically increases the efficiency lentiviral transcription. Residual analysis Tat critical vector quality safety....