A5014466478- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- T-cell and B-cell Immunology
- Herpesvirus Infections and Treatments
- Hematopoietic Stem Cell Transplantation
- Toxoplasma gondii Research Studies
- Viral-associated cancers and disorders
- Immunotherapy and Immune Responses
- Cellular transport and secretion
- Glycosylation and Glycoproteins Research
- Calcium signaling and nucleotide metabolism
- HIV Research and Treatment
- CAR-T cell therapy research
- Vasculitis and related conditions
- Eosinophilic Disorders and Syndromes
- Tumors and Oncological Cases
- Indigenous Health, Education, and Rights
- Genetics and Neurodevelopmental Disorders
- Bartonella species infections research
- Metabolism, Diabetes, and Cancer
- Cancer and Skin Lesions
- Cancer Research and Treatments
- Cancer Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Biochemical and Structural Characterization
Medical College of Wisconsin
2011-2024
Smith Clinic
2021
Mayo Clinic
2019
Murdoch Children's Research Institute
2019
Harvard University
1992-2004
Yale University
1997
Howard Hughes Medical Institute
1997
Abstract Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, additional associations conditional false discovery rate approach. Many variants are also associated asthma six...
Synaptojanin 1 is an inositol 5‐phosphatase with a putative role in clathrin‐mediated endocytosis. Goal of this study was to provide new evidence for hypothesis. We show that synaptojanin concentrated at clathrin‐coated endocytic intermediates nerve terminals. Furthermore, we report synaptojanin‐170, alternatively spliced isoform 1, binds Eps15, clathrin coat‐associated protein. Binding mediated by the COOH‐terminal region synaptojanin‐170 which here be poorly conserved from rat humans, but...
A central issue for adoptive cellular immunotherapy is overcoming immunosuppressive signals to achieve tumor clearance. While γδ T cells are known be potent cytolytic effectors that can kill a variety of cancers, it not clear whether they inhibited by suppressive ligands expressed in microenvironments. Here, we have used powerful preclinical model where EBV infection drives the de novo generation human B cell lymphomas vivo, and autologous lymphocytes held check PD-1/CTLA-4–mediated...
An important paradigm in allogeneic hematopoietic cell transplantations (allo-HCTs) is the prevention of graft-versus-host disease (GVHD) while preserving graft-versus-leukemia (GVL) activity donor T cells. From an observational clinical study adult allo-HCT recipients, we identified a CD4 + /CD8 double-positive (DPT) population, not present starting grafts, whose presence was predictive ≥ grade 2 GVHD. Using established xenogeneic transplant model, reveal that DPT population develops from...
Angelman syndrome is a severe neurological disorder characterized by mental retardation, absent speech, ataxia, seizures, and hyperactivity. The gene affected in this UBE3A, the encoding E6-associated protein (E6AP) ubiquitin-protein ligase. Most patients have chromosomal deletions that remove entire maternal allele of UBE3A. However, small subset E6AP point mutations result single amino acid changes or short in-frame still allow translation full-length protein. By studying these E6AP, we...
GLUT1, the erythrocyte glucose transporter, and GLUT4, adipose/muscle were each expressed in NIH-3T3 cells by retrovirus-mediated gene transfer. In fibroblasts overexpressing basal as well insulin-stimulated deoxyglucose uptake was increased. Expression of GLUT4 without affect on either or hormone stimulated hexose uptake. Localization transporters indirect immunofluorescence revealed that, whereas GLUT1 found primarily cell surface, directed to vesicles a perinuclear distribution throughout...
The natural killer cell receptor NKG2D activates NK cells by engaging one of several ligands (NKG2DLs) belonging to either the MIC or ULBP families. Human cytomegalovirus (HCMV) UL16 and UL142 counteract this activation retaining NKG2DLs US18 US20 act via lysomal degradation but importance evasion for infection is unknown. Since are highly conserved in rhesus macaques, we characterized how NKG2DL interception (RhCMV) impacts vivo. Interestingly, RhCMV lacks homologs instead employs Rh159,...
Synaptotagmins, which have been found exclusively in neuroendocrine or exocrine tissues, implicated the regulation of secretory vesicle fusion with plasma membrane. The present paper describes a synaptotagmin isoform (synaptotagmin-5) exhibits 49% amino acid identity to synaptotagmin-1 and -2. Synaptotagmin-5 mRNA is expressed rat kidney, adipose tissue, lung, heart, as well at higher levels brain PC12 cells. Antiserum specific for synaptotagmin-5 recognizes protein about 50 kDa 6-fold more...
Herpesviruses have evolved numerous immune evasion strategies to facilitate establishment of lifelong persistent infections. Many herpesviruses encode gene products devoted preventing viral antigen presentation as a means escaping detection by cytotoxic T lymphocytes. The human herpesvirus-7 (HHV-7) U21 product, for example, is an immunoevasin that binds class I major histocompatibility complex molecules and redirects them the lysosomal compartment. Virus infection can also induce...
NBSGW mice are highly immunodeficient and carry a hypomorphic mutation in the c-kit gene, providing host environment that supports robust human hematopoietic expansion without pre-conditioning. These thus provide model to investigate engraftment absence of conditioning-associated damage. We compared transplantation CD34+ HSPCs purified from three different sources: umbilical cord blood, adult bone marrow G-CSF mobilized peripheral blood. blood were significantly more efficient (as function...
ABSTRACT All members of the herpesvirus family persist in their host throughout life. In doing so, herpesviruses exploit a surprising number different strategies to evade immune system. Human 7 (HHV-7) is relatively recently discovered member family, and little known about how it escapes detection. Here we show that HHV-7 infection results premature degradation major histocompatibility complex class I molecules. We identify characterize protein from HHV-7, U21, binds diverts properly folded...
Abstract Acute graft-versus-host disease (GVHD) is a frequent complication of hematopoietic transplantation, yet patient risk stratification remains difficult, and prognostic biomarkers to guide early clinical interventions are lacking. We developed an approach evaluate the potential human T cells from grafts produce GVHD. Nonconditioned NBSGW mice transplanted with titrated doses bone marrow GVHD that was characterized by widespread lymphocyte infiltration organ pathology. Interestingly,...
Herpesviruses have evolved numerous strategies to evade detection by the immune system. Notably, most of herpesviruses interfere with viral antigen presentation cytotoxic T lymphocytes (CTLs) removing class I major histocompatibility complex (MHC) molecules from infected cell surface. Clearly, since an extensive array mechanisms remove MHC surface, this strategy serves them well. However, often serve as inhibitory ligands for NK cells, so downregulation all should leave open attack. Some...
Like all members of the herpesvirus family, human herpesvirus‐7 has evolved mechanisms to evade immune detection. The gene product U21 encodes an immunoevasin that binds class I major histocompatibility complex molecules and diverts them a lysosomal compartment. Here we show cytoplasmic tail U21, although sufficient sequester heterologous membrane protein (CD4 chimera), no effect on U21's ability redirect lysosomes. Instead, ER‐lumenal domain is These observations demonstrate novel viral...
The U21 gene product from human herpesvirus 7 binds to and redirects class I major histocompatibility complex (MHC) molecules a lysosomal compartment. molecular mechanism by which reroutes MHC lysosomes is not known. Here, we have reconstituted the interaction between purified soluble molecules, suggesting that does require additional cellular proteins interact with molecules. Our results demonstrate U21, itself predicted contain an I-like protein fold, interacts tightly as tetramer, in 4:2...
Human herpesviruses-6 and -7 infect essentially 100% of the world's population before age 5 then remain latent or persistent in their host throughout life. As such, these viruses are among most pervasive stealthy all viruses.
The U21 open reading frame from human herpesvirus-7 encodes a membrane protein that associates with and redirects class I MHC molecules to the lysosomal compartment. mechanism by which accomplishes this trafficking excursion is unknown. Here we have examined contribution of localization, glycosylation, domain structure, absence substrate on ability traffic lysosomes. Our results suggest existence cellular necessary for U21-mediated rerouting molecules.
Many caribou populations are declining across the Circumpolar North, presenting challenges for many Indigenous Peoples who have deep and enduring relationships with this animal. In Labrador, Canada, herds recently experienced population declines, including George River herd, which has dropped by 99% from its peak, leading to enactment of a total hunting ban in 2013 issued Government Newfoundland Labrador. The decline subsequent affected various aspects Inuit well-being. Using Inuit-led...
Invariant natural killer T (iNKT) cells are a conserved population of innate lymphocytes that interact with key antigen-presenting to modulate adaptive T-cell responses in ways can either promote protective immunity, or limit pathological immune activation. Understanding the immunological networks engaged by iNKT mediate these opposing functions is pre-requisite effectively using for therapeutic applications. Using human umbilical cord blood xenotransplantation model, we show here...
Herpes viruses are known for infecting epithelial cells and manifesting as vesicles. However, herpes can also infect stromal cells. While established in the ocular setting, cutaneous (deep herpes) is previously unreported may evade clinical microscopic detection. We searched skin biopsies with disease. Clinical information was retrieved via electronic medical records pathology system. Hematoxylin eosin slides, immunohistochemical staining, polymerase chain reaction detection of viral DNA...