A5001857296- Diabetes and associated disorders
- Pancreatic function and diabetes
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Diabetes Management and Research
- Adipokines, Inflammation, and Metabolic Diseases
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Xenotransplantation and immune response
- Monoclonal and Polyclonal Antibodies Research
- CRISPR and Genetic Engineering
- CAR-T cell therapy research
- Inflammatory Biomarkers in Disease Prognosis
- Liver Disease Diagnosis and Treatment
- Immune cells in cancer
- Diabetes Treatment and Management
- Aldose Reductase and Taurine
- Pharmacology and Obesity Treatment
- Endoplasmic Reticulum Stress and Disease
- Cannabis and Cannabinoid Research
- Antimicrobial Peptides and Activities
- Genetic Syndromes and Imprinting
- Epigenetics and DNA Methylation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
University of Pittsburgh
2006-2023
Carnegie Mellon University
2017-2023
Allegheny Health Network
2015-2022
Allegheny-Singer Research Institute
2021-2022
Parks Victoria
2020
Allegheny General Hospital
2017-2019
Children's Hospital of Pittsburgh
2002-2014
Immungenetics (Germany)
2008-2011
University of Pittsburgh Medical Center
2011
Diabetes Australia
2005
The safety of dendritic cells to selectively suppress autoimmunity, especially in type 1 diabetes, has never been ascertained. We investigated the autologous cells, stabilized into an immunosuppressive state, established adult diabetic patients.A randomized, double-blind, phase I study was conducted. A total 10, otherwise generally healthy, insulin-requiring patients between 18 and 60 years age, without any other known or suspected health conditions, received unmanipulated engineered ex vivo...
Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that inhibits β cell function and promotes Fas-triggered apoptosis. IL-1β thought to act early in the initiation of autoimmune destruction pancreatic cells type I diabetes. impairment, part, by activating NF-κB transcription factor-dependent signaling pathways. We have examined whether could be protected from effects overexpressing an inhibitor activity, IκB, adenoviral gene transfer intact human islets culture. Infection with vector...
OBJECTIVE Macrophages play an important role in the pathogenesis of insulin resistance via production proinflammatory cytokines. Our goal is to decipher molecular linkage between cytokine and macrophages. RESEARCH DESIGN AND METHODS We determined profiles cultured macrophages identified interleukin (IL)-1β gene as a potential target FoxO1, key transcription factor that mediates action on expression. studied mechanism by which FoxO1 insulin-dependent regulation IL-1β expression correlated...
Excessive endogenous glucose production contributes to fasting hyperglycemia in diabetes. This effect stems from inept insulin suppression of hepatic gluconeogenesis. To understand the underlying mechanisms, we studied ability forkhead box O6 (FoxO6) mediate action on gluconeogenesis and its contribution metabolism.We characterized FoxO6 metabolism cultured hepatocytes rodent models dietary obesity, resistance, or insulin-deficient We determined genetically modified mice with gain- versus...
Abstract Phenotypically “immature” dendritic cells (DCs), defined by low cell surface CD40, CD80, and CD86 can elicit host immune suppression in allotransplantation autoimmunity. Herein, we report the most direct means of achieving phenotypic immaturity NOD bone marrow-derived DCs aiming at preventing diabetes syngeneic recipients. molecules were specifically down-regulated treating ex vivo with a mixture antisense oligonucleotides targeting primary transcripts. The incidence was...
The beta-cells in the pancreatic islets of Langerhans are targets autoreactive T-cells and destroyed type 1 diabetes. Macrophage-derived interleukin-1beta (IL-1beta) is important eliciting beta-cell dysfunction initiating damage response to microenvironmental changes within islets. In particular, IL-1beta can impair glucose-stimulated insulin production vitro sensitize them Fas (CD95)/FasL-triggered apoptosis. this report, we have examined ability block detrimental effects by genetically...
Dendritic cells (DC) classically promote immune responses but can be manipulated to induce antigen-specific hyporesponsiveness in vitro. The expression of costimulatory molecules (CD40, CD86, CD80) at the DC cell surface correlates with their capacity or suppress responses. Expression these is associated NF-kB-dependent transcription genes. tolerogenicity has been impaired genes as well NF-kB translocation nucleus. In this report, we demonstrate that double-stranded oligodeoxyribonucleotides...
Background A peptide able to transduce cardiac tissue specifically, delivering cargoes the heart, would be of significant therapeutic potential for delivery small molecules, proteins and nucleic acids. In order identify peptide(s) heart tissue, biopanning was performed in cell culture vivo with a M13 phage display library. Methods Results cardiomyoblast line, H9C2, incubated 12 amino acid Internalized recovered, amplified then subjected total three rounds where infectious isolated from...
The performance of an in situ-forming injectable membrane designed to retain antibody molecules vivo is described. system entails aqueous mixture peptide amphiphiles (referred as"EAK16-II" and "EAKH6") intermediate proteins (anti-H6 protein A/G) through which therapeutic IgG are colocalized oriented. Scanning electron micrographs show localized on the EAK16-II/EAKH6 membrane. were captured via specific interactions remained biologically active vitro. Upon administration into mice...
This study was aimed at ascertaining the efficacy of antisense oligonucleotide-formulated microspheres to prevent type 1 diabetes and reverse new-onset disease.Microspheres carrying oligonucleotides CD40, CD80, CD86 were delivered into NOD mice. Glycemia monitored determine disease prevention reversal. In recipients that remained and/or became free, spleen lymph node T-cells enriched prevalence Foxp3(+) putative regulatory (Treg cells). Splenocytes from diabetes-free microsphere-treated...
Dendritic cells can facilitate allograft survival and prevent autoimmunity via direct indirect cell-mediated mechanisms. Recent studies demonstrate that immunoregulatory dendritic (iDCs) confer immune hyporesponsiveness in part through CD4(+) CD25(+) T regulatory (Tregs). Herein, we provide evidence to support the hypothesis derived from NOD mice engineered ex vivo exhibit suppressed expression of CD40, CD80, CD86 costimulatory molecules motivate an increase prevalence T-cells interleukin...
Cellular therapies with CD4+ T regulatory cells (Tregs) hold promise of efficacious treatment for the variety autoimmune and allergic diseases as well post-transplant complications. Nevertheless, current manufacturing Tregs a cellular medicinal product varies between different laboratories, which in turn hampers precise comparisons results studies performed. While number clinical trials testing is already substantial, it seems to be crucial provide some standardised characteristics Treg...
Abnormalities of dendritic cells (DCs) have been identified in type 1 diabetic patients and nonobese (NOD) mice that are associated with augmented nuclear transcription factor (NF)-κB activity. An imbalance favors development the immunogenic DCs may predispose to disease, restoration balance by administration deficient NF-κB activity prevent diabetes. propagated from NOD mouse bone marrow treated NF-κB–specific oligodeoxyribonucleotide (ODN) vitro (NF-κB ODN DC) were assessed for efficacy...
Summary While much is known about tolerogenic dendritic cell effects on forkhead box protein 3 (FoxP3)+ regulatory T cells, virtually nothing their another arm of immunoregulation that mediated by a subpopulation immunosuppressive B cells. These cells suppress rheumatoid arthritis, lupus and inflammatory bowel disease in mice, functional defects have been reported human lupus. We show co-stimulation-impaired prevent reverse type 1 diabetes mellitus induce the proliferation vitro. also...
Cellular therapies with tolerogenic antigen-presenting cells (tolAPC) show great promise for the treatment of autoimmune diseases and prevention destructive immune responses after transplantation. The methodologies generating tolAPC vary greatly between different laboratories, making it difficult to compare data from studies; thus constituting a major hurdle development standardised therapeutic products. Here we describe an initiative by members field generate minimum information model...