Faculty Bibliography
Searched for:
person:alum01 or dabovb01 or mezzav01 or dbh274 or loomic01 or selvas05 or dewanz01
Total Results:
168
Bone marrow derived cells populate post-ablation scar tissue and couple to surrounding myocardium [Meeting Abstract]
Introduction: Post-ablation scarring is used as a method to uncouple and/or silence pro-arrhythmic circuits. It has been previously suggested that circulating bone marrow derived cells (BMDC) are capable of homing into myocardial infarction scars. It is possible that intercellular junctions form between myocytes and BMDCs and may contribute to ablation failure and recurrence of arrhythmias. Methods: We tested whether BMDCs populate an ablation scars and contribute to functional coupling between the scar and surrounding myocardium. Wild type C57BI/6 mice (n=17) underwent radiation-induced myeloablation and subsequent transplantation with bone marrow progenitors obtained from fetal Cx43 WT (bmcWT) or Cx43 deficient (bmcKO) mice. Results: All donor cells constitutively expressed mCherry protein. Right ventricular ablation was carried out thirty days post transplantation and hearts were studied 30 day post ablation. Cells expressing mCherry and vimentin were observed throughout the scar suggesting donor cells differentiated into a mesenchymal lineage. Coupling between the uninjured myocardium and the scar was assayed with optical mapping. Suction electrode was placed on uninjured myocardium next to the scar to deliver current pulses. Conclusions: Changes in membrane voltage were measured optically at three different sites: Uninjured myocardium, Scar and Remote area (see figure). These data demonstrate that BMDCs can couple to the surrounding myocardium and contribute to the electrophysiological properties of ablation scar tissue. Delivery of modified BMDCs could be used to modifythe post-ablation scar electrophysiological properties. (Figure Presented)
EMBASE:72283867
ISSN: 1556-3871
CID: 2150962
Sonic Hedgehog (shh) Signaling Regulates Myofibroblast Function During Alveolar Septum Formation In Postnatal Lung [Meeting Abstract]
ISI:000390749601588
ISSN: 1535-4970
CID: 2414542
Progress in biophysics & molecular biology. 2016:120(1-3):128-33.DOI: 10.1016/j.pbiomolbio.2015.12.006
A review of the literature on cardiac electrical activity between fibroblasts and myocytes
Myocardial injuries often lead to fibrotic deposition. This review presents evidence supporting the concept that fibroblasts in the heart electrically couple to myocytes.
PMCID:4808420
PMID: 26713556
ISSN: 1873-1732
CID: 1895142
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
Methylation profiling of locally advanced rectal cancer (LARC): Exploration of potential predictive markers for neoadjuvant chemoradiation (NACR). [Meeting Abstract]
ISI:000378109600591
ISSN: 1527-7755
CID: 2169652
Proceedings of the National Academy of Sciences of the United States of America (PNAS). 2015:112(45):14012-7.DOI: 10.1073/pnas.1507652112
Genetic analysis of the contribution of LTBP-3 to thoracic aneurysm in Marfan syndrome
Marfan syndrome (MFS) is an autosomal dominant disorder of connective tissue, caused by mutations of the microfibrillar protein fibrillin-1, that predisposes affected individuals to aortic aneurysm and rupture and is associated with increased TGFbeta signaling. TGFbeta is secreted from cells as a latent complex consisting of TGFbeta, the TGFbeta propeptide, and a molecule of latent TGFbeta binding protein (LTBP). Improper extracellular localization of the latent complex can alter active TGFbeta levels, and has been hypothesized as an explanation for enhanced TGFbeta signaling observed in MFS. We previously reported the absence of LTBP-3 in matrices lacking fibrillin-1, suggesting that perturbed TGFbeta signaling in MFS might be due to defective interaction of latent TGFbeta complexes containing LTBP-3 with mutant fibrillin-1 microfibrils. To test this hypothesis, we genetically suppressed Ltbp3 expression in a mouse model of progressively severe MFS. Here, we present evidence that MFS mice lacking LTBP-3 have improved survival, essentially no aneurysms, reduced disruption and fragmentation of medial elastic fibers, and decreased Smad2/3 and Erk1/2 activation in their aortas. These data suggest that, in MFS, improper localization of latent TGFbeta complexes composed of LTBP-3 and TGFbeta contributes to aortic disease progression.
PMCID:4653215
PMID: 26494287
ISSN: 1091-6490
CID: 1810602
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
Latent TGF-beta-binding proteins
The LTBPs (or latent transforming growth factor beta binding proteins) are important components of the extracellular matrix (ECM) that interact with fibrillin microfibrils and have a number of different roles in microfibril biology. There are four LTBPs isoforms in the human genome (LTBP-1, -2, -3, and -4), all of which appear to associate with fibrillin and the biology of each isoform is reviewed here. The LTBPs were first identified as forming latent complexes with TGFbeta by covalently binding the TGFbeta propeptide (LAP) via disulfide bonds in the endoplasmic reticulum. LAP in turn is cleaved from the mature TGFbeta precursor in the trans-golgi network but LAP and TGFbeta remain strongly bound through non-covalent interactions. LAP, TGFbeta, and LTBP together form the large latent complex (LLC). LTBPs were originally thought to primarily play a role in maintaining TGFbeta latency and targeting the latent growth factor to the extracellular matrix (ECM), but it has also been shown that LTBP-1 participates in TGFbeta activation by integrins and may also regulate activation by proteases and other factors. LTBP-3 appears to have a role in skeletal formation including tooth development. As well as having important functions in TGFbeta regulation, TGFbeta-independent activities have recently been identified for LTBP-2 and LTBP-4 in stabilizing microfibril bundles and regulating elastic fiber assembly.
PMCID:4844006
PMID: 25960419
ISSN: 1569-1802
CID: 1803052
American journal of physiology. Heart & circulatory physiology. 2015:309(4):H553-4.DOI: 10.1152/ajpheart.00511.2015
New insights into the complex effects of KChIP2 on calcium transients
PMCID:4537948
PMID: 26163446
ISSN: 1522-1539
CID: 1668582
Latent transforming growth factor binding protein 4 regulates transforming growth factor beta receptor stability
Mutations in the gene for the latent transforming growth factor beta binding protein 4 (LTBP4) cause autosomal recessive cutis laxa type 1C. To understand the molecular disease mechanisms of this disease, we investigated the impact of LTBP4 loss on transforming growth factor beta (TGFbeta) signaling. Despite elevated extracellular TGFbeta activity, downstream signaling molecules of the TGFbeta pathway, including pSMAD2 and pERK, were down-regulated in LTBP4 mutant human dermal fibroblasts. In addition, TGFbeta receptors 1 and 2 (TGFBR1 and TGFBR2) were reduced at the protein but not at the ribonucleic acid level. Treatment with exogenous TGFbeta1 led to an initially rapid increase in SMAD2 phosphorylation followed by a sustained depression of phosphorylation and receptor abundance. In mutant cells TGFBR1 was co-localized with lysosomes. Treatment with a TGFBR1 kinase inhibitor, endocytosis inhibitors or a lysosome inhibitor, normalized the levels of TGFBR1 and TGFBR2. Co-immunoprecipitation demonstrated a molecular interaction between LTBP4 and TGFBR2. Knockdown of LTBP4 reduced TGFbeta receptor abundance and signaling in normal cells and supplementation of recombinant LTBP4 enhanced these measures in mutant cells. In a mouse model of Ltbp4 deficiency, reduced TGFbeta signaling and receptor levels were normalized upon TGFBR1 kinase inhibitor treatment. Our results show that LTBP4 interacts with TGFBR2 and stabilizes TGFbeta receptors by preventing their endocytosis and lysosomal degradation in a ligand-dependent and receptor kinase activity-dependent manner. These findings identify LTBP4 as a key molecule required for the stability of the TGFbeta receptor complex, and a new mechanism by which the extracellular matrix regulates cytokine receptor signaling.
PMCID:4476448
PMID: 25882708
ISSN: 1460-2083
CID: 1640232
