A5037847207- Pancreatic function and diabetes
- Diabetes and associated disorders
- Diabetes Management and Research
- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Pancreatitis Pathology and Treatment
- Pancreatic and Hepatic Oncology Research
- Celiac Disease Research and Management
- Mass Spectrometry Techniques and Applications
- Analytical Chemistry and Chromatography
- Immune Response and Inflammation
- AI in cancer detection
- Lung Cancer Treatments and Mutations
- CAR-T cell therapy research
- Chemokine receptors and signaling
- Viral Infections and Immunology Research
- Immune Cell Function and Interaction
- Advanced Proteomics Techniques and Applications
- T-cell and Retrovirus Studies
- RNA regulation and disease
- Cancer, Hypoxia, and Metabolism
- Lymphatic System and Diseases
- Chronic Lymphocytic Leukemia Research
University of Florida
2017-2025
Research Network (United States)
2020
Clinical Research of South Florida
2019
Breakthrough T1D
2016
Duke University
2007
Duke University Hospital
2007
Duke Medical Center
2007
University of South Florida
2002-2006
Moffitt Cancer Center
2003-2006
Tomsk Cancer Research Institute
1998
Purpose RRM1 encodes the regulatory subunit of ribonucleotide reductase and is a molecular target gemcitabine. Previous studies showed increased expression on continuous exposure cell lines to gemcitabine suggested improved survival for patients with low as opposed high tumoral when treated gemcitabine-containing chemotherapy. However, principal hypothesis that intratumoral levels gene are associated disease response has not been addressed. Patients Methods We constructed genetically...
Abstract Aims/hypothesis Earlier studies of pancreases from donors with type 1 diabetes demonstrated enteroviral capsid protein VP1 in beta cells. In the context a multidisciplinary approach undertaken by nPOD-Virus group, we assessed positivity pancreas and other tissues (spleen, duodenum pancreatic lymph nodes) 188 organ donors, including expressing autoantibody risk markers. We also investigated whether is linked to hyperexpression HLA class I (HLA-I) molecules islet Methods Organ donor...
Abstract Aims/hypothesis Previous pathology studies have associated enterovirus infections with type 1 diabetes by examining the capsid protein (VP1) in autopsy pancreases obtained near diagnosis. The Network for Pancreatic Organ Donors Diabetes (nPOD) has since from organ donors (with broad age and disease duration) disease-associated autoantibodies (AAbs), latter representing preclinical disease. Two accompanying manuscripts nPOD-Virus Group report primary data a coordinated analysis of...
Currently, a blood test for lung cancer does not exist. Serum biomarkers that could aid clinicians in making case management decisions would be enormously valuable. We used two proteomic platforms and literature search to select candidate serum markers the diagnosis of cancer.We initially assayed six proteins, four discovered by proteomics previously known associated, on training set sera from 100 patients (50 with new 50 age- sex-matched controls). Classification Regression Tree (CART)...
In type 1 diabetes (T1D), autoimmune destruction of pancreatic β cells leads to insulin deficiency and loss glycemic control. However, knowledge about human pancreas pathophysiology in T1D remains incomplete. To address this limitation, we established a tissue slice platform donor organs with without diabetes, facilitating the first live cell studies pathogenesis our knowledge. We show that slices from organ donors allow thorough assessment processes critical for disease development,...
Abstract Autoimmune β-cell destruction leads to type 1 diabetes, but the pathophysiological mechanisms remain unclear. To help address this void, we created an open-access online repository, unprecedented in its size, composed of large-scale electron microscopy images (‘nanotomy’) human pancreas tissue obtained from Network for Pancreatic Organ donors with Diabetes (nPOD; www.nanotomy.org ). Nanotomy allows analyses complete donor islets up macromolecular resolution. Anomalies found diabetes...
Concerns that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of disease 2019 (COVID-19), may cause new-onset diabetes persist in an evolving research landscape, and precise risk assessment is hampered by, at times, conflicting evidence. Here, leveraging comprehensive single-cell analyses vitro SARS-CoV-2-infected human pancreatic islets, we demonstrate productive strictly dependent on SARS-CoV-2 entry receptor ACE2 targets practically all...
Nuclear morphology is an indicator of cellular function and disease states, as changes in nuclear size, shape, texture often reflect underlying disease-related genetic, epigenetic, microenvironmental alterations. For diagnosis, segmentation performed 2D hematoxylin eosin (H&E)-stained tissue sections has long represented the gold standard. However, recent advances three-dimensional (3D) histology, which provide a more biologically accurate representation spatial heterogeneity human...
Type 2 diabetes mellitus (T2D) is a chronic age-related disorder characterized by hyperglycemia due to the failure of pancreatic beta cells compensate for increased insulin demand. Despite decades research, pathogenic mechanisms underlying T2D remain poorly defined. Here, we use imaging mass cytometry (IMC) with panel 34 antibodies simultaneously quantify markers exocrine, islet, and immune stromal components. We analyze over million from 16 pancreata obtained donors 13 age-similar...
Abstract The culture of live pancreatic tissue slices is a powerful tool for the interrogation physiology and pathology in an vitro setting that retains near-intact cytoarchitecture. However, current conditions human (HPSs) have only been tested short-term applications, which are not permissive long-term, longitudinal study endocrine regeneration. Using system designed to mimic physiological oxygenation pancreas, we demonstrate high viability preserved exocrine function HPS at least 10 days...
Type 1 diabetes (T1D) is a progressive autoimmune condition that culminates in the loss of insulin-producing beta cells. Pancreatic histopathology provides essential insights into disease initiation and progression yet an integrated perspective situ pathogenic processes lacking due to limited sample availability, dispersed nature anatomical lesions, often restricted analytical dimensionality. Here, we combined multiplexed immunostaining, high-magnification whole-slide imaging, digital...
Summary Recent 3D analyses reported abundant, small beta-cell-rich endocrine objects (EOs) in the human pancreas. Here, we assessed morphological parameters of >262,000 EOs pancreas sections from 220 donors with or without type 1 diabetes (T1D), ranging age and disease duration. We observe many insulin (Ins)+/glucagon (Gluc)-EOs diabetes. Their relative contribution to total area is greatest early life (0-2y) but reduces thereafter. Strikingly, show virtual absence Ins+Gluc- individuals...
Abstract Cell type-specific regulatory programs that drive type 1 diabetes (T1D) in the pancreas are poorly understood. Here we performed single nucleus multiomics and spatial transcriptomics up to 32 non-diabetic (ND), autoantibody-positive (AAB+), T1D donors. Genomic profiles from 853,005 cells mapped 12 pancreatic cell types, including multiple exocrine sub-types. Beta, acinar, other related cellular niches, had altered abundance gene activity progression, distinct pathways AAB+ compared...
The natural history and pathogenesis of type 1 diabetes, particularly during the autoantibody-positive stages preceding clinical onset, are not well understood, in part, due to limited availability human pancreatic samples. Here, we studied 88 organ donors, including 28 single 10 multiple by imaging mass cytometry. Approximately 10,000 islets 16 million single-cells were spatially analyzed using 79 antibodies revealing both β-cell states islet-immune interface. We identified IAPP loss from...
Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in individuals with diabetes. Individuals type 1 diabetes have two- to fourfold higher risk CVD comparison the general population, driven by an earlier onset increased lifetime incidence events mortality. Similarly, 2 confers threefold risk, usually alongside metabolic syndrome, obesity, hypertension. Despite advancements methods for achieving glycemic control, burden remains disproportionately high The mechanisms...
Large granular lymphocyte (LGL) leukemia is a lymphoproliferative disease often associated with autoimmune disorders such as rheumatoid arthritis. High levels of soluble Fas ligand have been implicated in development chronic neutropenia. However, comprehensive analysis constitutive chemokine and lymphokine production LGL has not previously reported. Here, we utilized RNase protection assays enzyme-linked immunosorbent (ELISAs) to address this question. RANTES, IL-8, MIP-1alpha, MIP-1beta,...
Large granular lymphocyte (LGL) leukemia is a lymphoproliferative disorder often associated with rheumatoid arthritis. The etiology of LGL not known. In order to better understand the pathogenesis leukemia, we analyzed differential gene expression using microarray technology. We found that approximately 80 genes were up-regulated and 12 down-regulated when compared normal peripheral blood mononuclear cells (PBMC). present study, interested in group involved cytotoxic function. function...
Within the human pancreas, exocrine and endocrine cells control secretion of digestive enzymes production hormones to maintain metabolic homeostasis, respectively. While vast majority type 1 diabetes research efforts have focused on function autoimmunity, recent studies identified a series unique features (e.g., reduced weight volume, increased density leukocytes) within pancreas in this disease, but mechanisms underlying these aberrancies are unknown. Therefore, we histologically assessed...
Abstract Aims Misclassification of diabetes is common due to an overlap in the clinical features type 1 and 2 diabetes. Combined diagnostic models incorporating biomarker information have recently been developed that can aid classification, but they not validated using pancreatic pathology. We evaluated a model against histologically defined Methods classified cases from Network for Pancreatic Organ donors with Diabetes (nPOD) biobank as ( n = 111) or non‐type 42) histopathology. Type was by...
Abstract The Network for Pancreatic Organ donors with Diabetes (nPOD) is the largest biorepository of human pancreata and associated immune organs from type 1 diabetes (T1D), maturity-onset young (MODY), cystic fibrosis-related (CFRD), 2 (T2D), gestational diabetes, islet autoantibody positivity (AAb+), without diabetes. nPOD recovers, processes, analyzes, distributes high-quality biospecimens, collected using optimized standard operating procedures, de-identified data/metadata to...