A5050919306- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Pancreatic function and diabetes
- Immunotherapy and Immune Responses
- Diabetes and associated disorders
- Monoclonal and Polyclonal Antibodies Research
- Diabetes Management and Research
- Cannabis and Cannabinoid Research
- Diabetes Treatment and Management
- Metabolism, Diabetes, and Cancer
- Virus-based gene therapy research
- Diet and metabolism studies
- RNA Interference and Gene Delivery
- Reproductive System and Pregnancy
- Diet, Metabolism, and Disease
- Genetics and Neurodevelopmental Disorders
- Immune Response and Inflammation
- T-cell and Retrovirus Studies
- CAR-T cell therapy research
- vaccines and immunoinformatics approaches
- Chronic Myeloid Leukemia Treatments
- Cell Adhesion Molecules Research
- Viral Infectious Diseases and Gene Expression in Insects
- Animal Genetics and Reproduction
- NF-κB Signaling Pathways
Columbia University
1994-2019
Columbia University Irving Medical Center
2007-2019
Institute of Genetics and Biophysics
1998-2015
University of Oxford
2013
University of Naples Federico II
2011
National Research Council
2009
Universitat Autònoma de Barcelona
1996
Instituto di Biofisica
1996
Ludwig Cancer Research
1988-1989
T cells from an HLA-DR11/DR12 responder were stimulated in mixed lymphocyte culture with carrying the DR1 antigen. After priming, proliferated response to both DR1-positive-stimulating and a peptide derived polymorphic region of HLA-DR beta 1*0101 chain presented by responder's antigen-presenting (APC). The dominant epitope recognized primed corresponded residue 21-42 was HLA-DR12 peptide-reactive express cell receptor V 3. results demonstrate that allopeptides processing presentation donor...
Diabetes results from an absolute or relative reduction in pancreatic beta cell mass (BCM) leading to insufficient insulin secretion and hyperglycemia. Measurement of secretory capacity is currently used as a surrogate measure BCM. However, serum concentrations provide imprecise index BCM, no reliable noninvasive BCM available. Type 2 vesicular monoamine transporters (VMAT2) are expressed human islet cells, well tissues the CNS. [11C]Dihydrotetrabenazine ([11C]DTBZ) binds specifically VMAT2...
Type 2 vesicular monoamine transporter (VMAT2), found in the brain, is also expressed by β-cells of pancreas association with insulin. Preclinical experiments suggested that <sup>11</sup>C-dihydrotetrabenazine PET–measured VMAT2 binding might serve as a biomarker β-cell mass. We evaluated feasibility PET quantification pancreatic healthy subjects and patients long-standing type 1 diabetes. <b>Methods:</b><sup>11</sup>C-Dihydrotetrabenazine was performed on 6 9 controls. potential...
RJ 2.2.5 is a human B cell line that has lost the capacity to express MHC class II genes. The II-positive phenotype restored in somatic hybrids between and mouse spleen cells. By karyotype molecular studies of an informative family we have now shown reexpression gene products, as well maintenance phenotype, correlates with presence chromosome 16. Thus, existence on this newly found locus, designated by us aIr-1, determines trans-acting activator function for expression, established. Possible...
We describe a negative feedback autocrine regulatory circuit for glucose-stimulated insulin secretion in purified human islets vitro. Using chronoamperometry and vitro measurements, evidence is provided that dopamine (DA), which loaded into insulin-containing secretory granules by vesicular monoamine transporter type 2 β-cells, released response to glucose stimulation. DA then acts as regulator of via its action on D2R, are also expressed β-cells. found antagonism receptors participating...
Abstract The purpose of our study was to identify transcripts specific for tissue-restricted, membrane-associated proteins in human islets that, turn, might serve as markers healthy or diseased islet cell masses. Using oligonucleotide chips, we obtained gene expression profiles comparison with the exocrine pancreas, liver, and kidney tissue. As periislet presence type 1 interferon is associated development diabetes, profile treated ex vivo interferon-α2β (IFNα2β) also determined. A set genes...
Human islet β-cells exploit an autocrine dopamine (DA)-mediated inhibitory circuit to regulate insulin secretion. β-Cells also express the DA active transporter and large neutral amino acid heterodimer enabling them import circulating or its biosynthetic precursor, L-3,4-dihydroxyphenylalanine (L-DOPA). The capacity L-DOPA from extracellular space possibly indicates that may be endocrine signal as well. In humans, a mixed meal stimulus is accompanied by contemporary serum excursions of...
We hypothesized that DA and L-DOPA derived from nutritional tyrosine the resultant observed postprandial plasma excursions of might affect glucose tolerance via their ability to be taken-up by beta cells inhibit glucose-stimulated β-cell insulin secretion. To investigate a possible circuit between meal-stimulated 3,4-dihydroxy-L-phenylalanine (L-DOPA) dopamine (DA) production in GI tract pancreatic β-cells, we: 1) mapped mucosal expression hydroxylase (TH) aromatic amino acid decarboxylase...
Constitutive expression of major histocompatibility complex class II genes is acquired very early in B-cell ontogeny and maintained up to the blast stage. Terminal differentiation plasma cells is, however, accompanied by a loss gene expression. In B this system under control several loci encoding transacting factors with activator function, one which, aIr-1 product, operates across species barriers. report human shown be extinguished somatic cell hybrids between II-positive line Raji mouse...
The common pathology underlying both type 1 and 2 diabetes (T1DM T2DM) is insufficient β‐cell mass (BCM) to meet metabolic demands. An important impediment the more rapid evaluation of interventions for T1DM T2DM lack biomarkers pancreatic BCM. A reliable means monitoring and/or function β‐cells would enable progression as well pharmacologic other interventions. Recently, we identified a biomarker BCM that quantifiable by positron emission tomography (PET). PET an imaging technique which...
Background. Because the hepatic portal system may not be optimal site for islet transplantation, several extrahepatic sites have been studied. Here, we examine an intramuscular transplantation site, bioengineered to better support neovascularization, engraftment, and survival, demonstrate that at this novel grafted beta cell mass quantitated in a real-time noninvasive manner by positron emission tomography (PET) imaging. Methods. Streptozotocin-induced rats were pretreated intramuscularly...
The vesicular monoamine transporter, type 2 (VMAT2) is expressed by insulin producing β cells and was evaluated as a biomarker of cell mass (BCM) positron emission tomography (PET) with [(18)F]fluoropropyl-dihydrotetrabenazine ([(18)F]FP-(+)-DTBZ).We the feasibility longitudinal pancreatic PET VMAT2 quantification in pancreas two studies healthy controls patients 1 or diabetes. binding potential (BPND) estimated voxelwise using reference tissue method cross-sectional study, followed...
To investigate the role of indirect pathway recognition in human allograft rejection, we have mapped dominant T cell determinant HLA-DRβ1*0101 molecule presented by DRβ1*1101 antigen. A synthetic peptide (pp 22–35) corresponding to sequence was used for testing frequency ofin vivoactivated cells graft and periphery. DRβ1*1101-positive patients carrying a heart mismatched HLA-DR1 antigen showed no reactivity pp 22–35 during quiescence. However, interleukin-2-responsive cells, which were...
In this study we investigated the molecular mechanisms responsible for extinction of constitutive MHC class II gene expression human B cells on somatic cell hybridization with murine plasmocytoma cells. We found that event is due to trans-acting suppressor functions mouse origin pre-existing in and acting at transcriptional level. Transcription entire family genes suppressed, including as DO beta which a distinct regulation had been previously demonstrated. Suppression appears specific...
Abstract Despite different embryological origins, islet β-cells and neurons share the expression of many genes display multiple functional similarities. One shared gene product, vesicular monoamine transporter type 2 (VMAT2, also known as SLC18A2), is highly expressed in human relative to other cells endocrine exocrine pancreas. Recent reports suggest that dopamine an important paracrine and/or autocrine regulator insulin release by β-cells. Given role VMAT2 economy monoamines such dopamine,...
Using cDNA arrays, we characterized patterns of gene expression in populations human dendritic cells (DCs) produced for clinical use. Culture and maturation induction myeloid adherent under serum‐free conditions yielded DCs with phenotypes similar to those described serum‐based systems. Analysis treated tumour necrosis factor alpha, soluble CD40L trimer or interferon gamma, however, showed specific each examined. Our studies document the several transcripts that have not hitherto been and/or...