A5054998121- Pancreatic function and diabetes
- Diabetes and associated disorders
- Immune cells in cancer
- Metabolism, Diabetes, and Cancer
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Diabetes Management and Research
- Pancreatic and Hepatic Oncology Research
- Angiogenesis and VEGF in Cancer
- Pluripotent Stem Cells Research
- Pancreatitis Pathology and Treatment
- Genetics and Neurodevelopmental Disorders
- Hedgehog Signaling Pathway Studies
- Wnt/β-catenin signaling in development and cancer
- Epigenetics and DNA Methylation
- Phagocytosis and Immune Regulation
- Immune Cell Function and Interaction
- NF-κB Signaling Pathways
- Single-cell and spatial transcriptomics
- Dietary Effects on Health
- Cell Image Analysis Techniques
- IL-33, ST2, and ILC Pathways
- Caveolin-1 and cellular processes
- Ultrasound and Hyperthermia Applications
- Lymphatic System and Diseases
Tel Aviv University
2015-2024
University of California, San Francisco
2008-2015
Weizmann Institute of Science
2002-2013
Massachusetts General Hospital
2005
Harvard University
2005
Howard Hughes Medical Institute
2005
New York University
2005
Hebrew University of Jerusalem
2000
Dendritic cells (DCs) and macrophages are critical to innate adaptive immunity the intestinal bacterial microbiota. Here, we identify a myeloid-derived mucosal DC in mice, which populates entire lamina propria of small intestine. Lamina DCs were found depend on chemokine receptor CX3CR1 form transepithelial dendrites, enable directly sample luminal antigens. was also control clearance entero-invasive pathogens by DCs. Thus, CX3CR1-dependent processes, host interactions specialized with...
The mononuclear phagocyte (MP) system is a body-wide macrophage (MΦ) and dendritic cell (DC) network, which contributes to tissue homeostasis, inflammation, immune defense. in vivo origins of MPs remain poorly understood. Here, we use an adoptive precursor transfer strategy into MP-depleted mice establish the differentiation sequence from recently identified MΦ/DC-restricted bone marrow (BM) (MDP) via BM blood intermediates peripheral MΦs DCs. We show that MDPs are precursors monocytes....
Abstract Peripheral blood monocytes are a population of circulating mononuclear phagocytes that harbor potential to differentiate into macrophages and dendritic cells. As in humans, the mouse comprise two phenotypically distinct subsets Gr1highCX3CR1int Gr1lowCX3CR1high, respectively. The question remains whether these populations contribute differentially generation peripheral phagocytes. In this study, we track fate adoptively transferred, fractionated monocyte lung recipient mice. We show...
Alveolar macrophages are a unique type of mononuclear phagocytes that populate the external surface lung cavity. Early studies have suggested alveolar originate from tissue-resident, local precursors, whereas others reported their derivation blood-borne cells. However, role circulating monocytes as precursors was never directly tested. In this study, we show through combined use conditional cell ablation and adoptive transfer in vivo blood monocytes. Interestingly, process requires an...
Abstract The lamina propria that underlies and stabilizes the gut lining epithelium is densely populated with strategically located mononuclear phagocytes. Collectively, these macrophages dendritic cells (DC) are believed to be crucial for tissue homeostasis as well innate adaptive host defense. Lamina DC were recently shown gain direct access intestinal lumen by virtue of epithelium-penetrating dendrites. However, role structures in pathogen uptake remains under debate. In this study, we...
The developing pancreatic epithelium gives rise to all endocrine and exocrine cells of the mature organ. During organogenesis, epithelial receive essential signals from overlying mesenchyme. Previous studies, focusing on ex vivo tissue explants or complete knockout mice, have identified an important role for mesenchyme in regulating expansion progenitor early pancreas epithelium. However, due lack genetic tools directing expression specifically mesenchyme, potential roles this supporting...
Adult neovascularization relies on the recruitment of monocytes to target organ or tumor and functioning therein as a paracrine accessory. The exact origins recruited mechanisms underlying their plasticity remain unclear. Using VEGF-based transgenic system in which genetically tagged are conditionally summoned liver part VEGF-initiated angiogenic program, we show that these cells derived from abundant pool circulating Ly6Chi monocytes. Remarkably, however, upon arrival at VEGF-induced organ,...
The heterogeneity of pancreatic ductal adenocarcinoma (PDAC) suggests that successful treatment might rely on simultaneous targeting multiple genes, which can be achieved by RNA interference-based therapeutic strategies. Here we show a potent combination microRNA and siRNA delivered an efficient nanocarrier to PDAC tumors. Using proteomic-microRNA profiles survival data patients from TCGA, found novel signature for prolonged survival. Accordingly, used microRNA-mimic increase miR-34a...
β-Cells rely on the islet microenvironment for their functionality and mass. Pericytes, along with endothelial cells, make up dense capillary network. However, although role of cells in supporting β-cell homeostasis has been vastly investigated, pericytes remains largely unknown. Here, we focus contribution to function. To this end, used a transgenic mouse system that allows diphtheria toxin-based depletion pericytes. Our results indicate islets depleted have reduced insulin content...
Abstract In vitro models of the pancreas can aid in developing therapies for pancreatic diseases. Nonetheless, most tissue engineering is limited to insulin‐secreting β‐cells or adenocarcinoma models. Combining all essential components, including exocrine, endocrine, and blood vasculature, crucial recapitulate native organization. this study, extrusion‐based 3D bioprinting create constructs containing both endocrine exocrine compartments exploited. Mouse pluripotent stem cell‐derived...
Abstract Vascular endothelial growth factor (VEGF) is one of the key factors regulating tumor angiogenesis and thus it primary targets for antiangiogenic therapy. The long‐term effects VEGF include induction proliferation migration cells, tube formation maintenance immature capillaries. early vasodilation increased permeability. We hypothesize that responses to can serve develop a quantitative measure activity VEGF, therefore may be applicable monitoring efficacy systemic suppression...
Although Hedgehog (Hh) signaling regulates cell differentiation during pancreas organogenesis, the consequences of pathway up-regulation in adult β-cells vivo have not been investigated. Here, we elevate Hh by expressing an active version GLI2 transcription factor, a mediator pathway, that are also devoid primary cilia, critical regulator activity. We show increased leads to impaired β-cell function and insulin secretion, resulting glucose intolerance transgenic mice. This phenotype was...
Islet transplantation has proven to be a successful strategy restore normoglycemia in patients with type 1 diabetes (T1D). However, the dearth of cadaveric islets available for hampers widespread application this treatment option. Although human embryonic stem cells and induced pluripotent are capable generating insulin-producing vitro when provided appropriate inductive cues, insulin-expressing that develop behave more like immature β-cells minimal sensitivity glucose stimulation. Here, we...
Abstract β-Cells depend on the islet basement membrane (BM). While some BM components are produced by endothelial cells (ECs), source of others remains unknown. Pancreatic pericytes directly support β-cells through mostly unidentified secreted factors. Thus, we hypothesized that regulate production components. Here, show produce multiple mouse pancreatic and interstitial matrices. Several pericyte-produced ECM were previously implicated in β-cell physiology, including collagen IV, laminins,...
Polymorphism in TCF7L2, a component of the canonical Wnt signaling pathway, has strong association with β-cell dysfunction and type 2 diabetes through mechanism that yet to be defined. β-Cells rely on cells their microenvironment, including pericytes, for proper function. Here, we show Tcf7l2 activity pancreatic pericytes is required Transgenic mice which was selectively inactivated exhibited impaired glucose tolerance due compromised function glucose-stimulated insulin secretion....
ABSTRACT Generating comprehensive image maps, while preserving spatial three-dimensional (3D) context, is essential in order to locate and assess quantitatively specific cellular features cell-cell interactions during organ development. Despite recent advances 3D imaging approaches, our current knowledge of the organization distinct cell types embryonic pancreatic tissue still largely based on two-dimensional histological sections. Here, we present a light-sheet fluorescence microscopy...