Faculty Bibliography
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114
Implementation of tissue clearing, fluorescence labeling, and imaging via lightsheet as a cross-core collaborative service [Meeting Abstract]
Recent developments in tissue clearing methods have provided investigators with an invaluable tool for visualizing and mapping three dimensional macromolecular structures and processes. By implementing a routine protocol, based on the passive clarity technique (PACT) method, for tissue clearing, the Research Histopathology Core at NYU Langone Medical Center seeks to provide investigators with a reliable, customizable service in conjunction with the immunohistochemistry (IHC) and Microscopy Cores in order to produce results in the most efficient way possible for both the investigators and the cores. The PACT method of clearing allows visualization of endogenous fluorescence and immunofluorescence labeling performed by the Core, or both. Stabilization through transparent hydrogel cross-linking, followed by delipidation in an sodium dodecyl sulfate buffer, results in a clear tissue sample that remains structurally sound with proteins, nucleic acids, and any associated labels in place. The clearing buffer can also be modified to allow simultaneous decalcification of bone specimens. Final clearing is achieved in a refractive index matching solution (RIMS buffer) which also serves as the microscopy medium. Cleared and labeled tissue can then be imaged on the Microscopy Core's Zeiss lightsheet microscope, allowing multichannel fluorescence from a range of angles and Z-stacking. The lightsheet microscope excites and detects only one thin optical section of the specimen at a time, making three dimensional imaging exceptionally light efficient. By honing proficiency in tissue clearing via the PACT method and working in close collaboration with neighboring core labs, the Histopathology Core can increase its breadth of expertise while relieving investigators of the time and cost intensive burden of protocol development and training.
EMBASE:613792615
ISSN: 0147-8885
CID: 2396962
Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF
PMCID:4755714
PMID: 26367794
ISSN: 1476-4687
CID: 1779142
American journal of respiratory cell & molecular biology. 2015:52(1):1-13.DOI: 10.1165/rcmb.2014-0132TR
Sonic Hedgehog Signaling in the Lung - from Development to Disease
Over the past two decades, the secreted protein sonic hedgehog (SHH) has emerged as a critical morphogen during embryonic lung development, regulating the interaction between epithelial and mesenchymal cell populations in both the airway and alveolar compartments. There is increasing evidence that the SHH pathway is active in adult lung diseases such as pulmonary fibrosis, asthma, chronic obstructive pulmonary disease (COPD) and lung cancer, which raises two questions: (1) what role does SHH signaling play in these diseases? (2) Is it a primary driver of the disease, or a response (perhaps beneficial) to the primary disturbance? In this review we aim to fill the gap between the well-studied period of embryonic lung development and the adult diseased lung by reviewing the HH pathway during the postnatal period, and in adult uninjured and injured lungs. We elucidate the similarities and differences in the epithelial-mesenchymal interplay during the fibrosis response to injury in lung compared to other organs, and present a critical appraisal of tools and agents available to evaluate HH signaling.
PMCID:4370254
PMID: 25068457
ISSN: 1044-1549
CID: 1089832
Expression Of Sonic Hedgehog Pathway Genes Is Different During Alveolarization And Maturation Phase In Postnatal Lung Development [Meeting Abstract]
ISI:000377582807337
ISSN: 1535-4970
CID: 2162152
Genetic Suppression of Inflammation Blocks the Tumor-Promoting Effects of TGF-beta in Gastric Tissue
The contributions of TGF-beta signaling to cancer are complex but involve the inflammatory microenvironment as well as cancer cells themselves. In mice encoding a TGF-beta mutant that precludes its binding to the latent TGF-beta binding protein (Tgfb1-/C33S), we observed multiorgan inflammation and an elevated incidence of various types of gastrointestinal solid tumors due to impaired conversion of latent to active TGF-beta1. By genetically eliminating activators of latent TGF-beta, we further lowered the amount of TGF-beta, which enhanced tumor frequency and multiorgan inflammation. This model system was used to further investigate the relative contribution of TGF-beta1 to lymphocyte-mediated inflammation in gastrointestinal tumorigenesis. Toward this end, we generated Tgfb1-/C33S;Rag2-/- mice that lacked adaptive immune function, which eliminated tumor production. Analysis of tissue from Tgfb1-/C33S mice indicated decreased levels of P-Smad3 compared to wild type animals, whereas tissue from Tgfb1-/C33S;Rag2-/- mice had normal P-Smad3 levels. Inhibiting the inflammatory response normalized levels of IL-1beta and IL-6 and reduced tumor cell proliferation. Additionally, Tgfb1-/C33S;Rag2-/- mice exhibited reduced paracrine signaling in the epithelia, mediated by hepatocyte growth factor produced by gastric stroma. Together, our results indicate that many of the responses of the gastric tissue associated with decreased TGF-beta1 may be directly or indirectly affected by inflammatory processes, which accompany loss of TGF-beta1, rather than a direct effect of loss of the cytokine.
PMCID:4158836
PMID: 24590056
ISSN: 0008-5472
CID: 831432
Allergic Contact Dermatitis to Gamma-Irradiated WEBCOL Alcohol Prep Pads
We report a case of allergic contact dermatitis to WEBCOL((R)) alcohol prep pads in a healthy 17-year-old girl who showed no reaction to the individual components of the prep pads upon provocative use testing. Although several case reports have described allergic contact dermatitis to isopropyl alcohol, there have been no reports of allergic contact dermatitis to alcohol prep pads sterilized with gamma irradiation, a common sterilization technique capable of producing volatile products in this type of alcohol prep pad.
PMID: 22471753
ISSN: 0736-8046
CID: 665962
Wnt activation in nail epithelium couples nail growth to digit regeneration
The tips of mammalian digits can regenerate after amputation, like those of amphibians. It is unknown why this capacity is limited to the area associated with the nail. Here we show that nail stem cells (NSCs) reside in the proximal nail matrix and that the mechanisms governing NSC differentiation are coupled directly with their ability to orchestrate digit regeneration. Early nail progenitors undergo Wnt-dependent differentiation into the nail. After amputation, this Wnt activation is required for nail regeneration and also for attracting nerves that promote mesenchymal blastema growth, leading to the regeneration of the digit. Amputations proximal to the Wnt-active nail progenitors result in failure to regenerate the nail or digit. Nevertheless, beta-catenin stabilization in the NSC region induced their regeneration. These results establish a link between NSC differentiation and digit regeneration, and suggest that NSCs may have the potential to contribute to the development of novel treatments for amputees.
PMCID:3936678
PMID: 23760480
ISSN: 0028-0836
CID: 426072
American journal of respiratory cell & molecular biology. 2013:48(6):703-10.DOI: 10.1165/rcmb.2012-0347OC
Hedgehog Signaling in Neonatal and Adult Lung
Sonic Hedgehog (Shh) signals from epithelium to mesenchyme during embryonic lung development, but the roles of Hedgehog (Hh) signaling in postnatal lung development and adult lung are not known. Using Gli1nlacZ reporter mice to identify cells with active Hh signaling, we found that Gli1nlacZ-positive mesenchymal cells are densely and diffusely present up to 2 weeks after birth and decline in number thereafter. In adult mice, Gli1nlacZ-positive cells are present around large airways and vessels and are sparse in alveolar septa. Hh-stimulated cells are mostly fibroblasts; only 10% of Gli1nlacZ-positive cells are smooth muscle cells, and most smooth muscle cells do not have activation of Hh signaling. After bleomycin injury there are abundant Gli1nlacZ-positive mesenchymal cells in fibrotic lesions and increased numbers of Gli1nlacZ-positive cells in preserved alveolar septa. Inhibition of Hh signaling with an antibody against all Hedgehog isoforms does not reduce bleomycin-induced fibrosis, but adenovirus-mediated over-expression of Shh increases collagen production in this model. Inhibition of Hh signaling during early postnatal lung development causes airspace enlargement without diminished alveolar septation. Reduction of Hh signaling in the later stages of postnatal lung development may be required for normal thinning and maturation of alveolar septa.
PMCID:3727871
PMID: 23371063
ISSN: 1044-1549
CID: 353072
Method for tracking core-contributed publications
Accurately tracking core-contributed publications is an important and often difficult task. Many core laboratories are supported by programmatic grants (such as Cancer Center Support Grant and Clinical Translational Science Awards) or generate data with instruments funded through S10, Major Research Instrumentation, or other granting mechanisms. Core laboratories provide their research communities with state-of-the-art instrumentation and expertise, elevating research. It is crucial to demonstrate the specific projects that have benefited from core services and expertise. We discuss here the method we developed for tracking core contributed publications.
PMCID:3468145
PMID: 23204927
ISSN: 1524-0215
CID: 197472
Regulation of cranial morphogenesis and cell fate at the neural crest-mesoderm boundary by engrailed 1
The characterization of mesenchymal progenitors is central to understanding development, postnatal pathology and evolutionary adaptability. The precise identity of the mesenchymal precursors that generate the coronal suture, an important structural boundary in mammalian skull development, remains unclear. We show in mouse that coronal suture progenitors originate from hedgehog-responsive cephalic paraxial mesoderm (Mes) cells, which migrate rapidly to a supraorbital domain and establish a unidirectional lineage boundary with neural crest (NeuC) mesenchyme. Lineage tracing reveals clonal and stereotypical expansion of supraorbital mesenchymal cells to form the coronal suture between E11.0 and E13.5. We identify engrailed 1 (En1) as a necessary regulator of cell movement and NeuC/Mes lineage boundary positioning during coronal suture formation. In addition, we provide genetic evidence that En1 functions upstream of fibroblast growth factor receptor 2 (Fgfr2) in regulating early calvarial osteogenic differentiation, and postulate that it plays an additional role in precluding premature osteogenic conversion of the sutural mesenchyme.
PMCID:3294437
PMID: 22395741
ISSN: 0950-1991
CID: 159856
