Child Health Institute of New Jersey

New Brunswick, NJ, United States

Child Health Institute of New Jersey

New Brunswick, NJ, United States
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Pang Z.P.,Child Health Institute of New Jersey | Han W.,Agency for Science, Technology and Research Singapore | Han W.,National University of Singapore
Bioscience Reports | Year: 2012

Energy homoeostasis, a co-ordinated balance of food intake and energy expenditure, is regulated by the CNS (central nervous system). The past decade has witnessed significant advances in our understanding of metabolic processes and brain circuitry which responds to a broad range of neural, nutrient and hormonal signals. Accumulating evidence demonstrates altered synaptic plasticity in the CNS in response to hormone signals. Moreover, emerging observations suggest that synaptic plasticity underlies all brain functions, including the physiological regulation of energy homoeostasis, and that impaired synaptic constellation and plasticity may lead to pathological development and conditions. Here, we summarize the current knowledge on the regulation of postsynaptic receptors such as AMPA (α-amino-3-hydroxy-5-methylisoxazole- 4-propionic acid), NMDA (N-methyl-D-aspartate) and GABA (γ-aminobutyric acid) receptors, and the presynaptic components by hormone signals. A detailed understanding of the neurobiological mechanisms by which hormones regulate energy homoeostasis may lead to novel strategies in treating metabolic disorders. © 2012 The Author(s).

Yi L.,Cancer Institute of New Jersey | Yi L.,Rutgers University | Lu C.,Child Health Institute of New Jersey | Hu W.,Cancer Institute of New Jersey | And 6 more authors.
Cancer Research | Year: 2012

The inactivation of p53 functions enhances the efficiency and decreases the latency of producing induced pluripotent stem cells (iPSC) in culture. The formation of iPSCs in culture starts with a rapid set of cell divisions followed by an epigenetic reprogramming of the DNA and chromatin. The mechanisms by which the p53 protein inhibits the formation of iPSCs are largely unknown. Using a temperature sensitive mutant of the p53 (Trp53) gene, we examined the impact of the temporal expression of wild type p53 in preventing stem cell induction from somatic cells.Wealso explored how different p53 mutant alleles affect the reprogramming process.Wefound that little or no p53 activity favors the entire process of somatic cell reprogramming. Reactivation of p53 at any time point during the reprogramming process not only interrupted the formation of iPSCs, but also induced newly formed stem cells to differentiate. Among p53-regulated genes, p21 (Cdkn1a), but not Puma (Bbc3) played a partial role in iPSCs formation probably by slowing cell division. Activation of p53 functions in iPSCs induced senescence and differentiation in stem cell populations. High rate of birth defects and increases in DNA methylation at the IGF2-H19 loci in female offspring of p53 knockout mice suggested that the absence of p53 may give rise to epigenetic instability in a stochastic fashion. Consistently, selected p53 missense mutations showed differential effects on the stem cell reprogramming efficiency in a c-Myc dependent manner. The absence of p53 activity and functions also contributed to an enhanced efficiency of iPSC production from cancer cells. The production of iPSCs in culture from normal and cancer cells, although different from each other in several ways, both responded to the inhibition of reprogramming by the p53 protein. Copyright © 2012 American Association for Cancer Research.

Wang Y.,Shanghai JiaoTong University | Chen X.,Shanghai JiaoTong University | Cao W.,Shanghai JiaoTong University | Shi Y.,Shanghai JiaoTong University | And 2 more authors.
Nature Immunology | Year: 2014

Mesenchymal stem cells (MSCs) are multipotent stromal cells that exist in many tissues and are capable of differentiating into several different cell types. Exogenously administered MSCs migrate to damaged tissue sites, where they participate in tissue repair. Their communication with the inflammatory microenvironment is an essential part of this process. In recent years, much has been learned about the cellular and molecular mechanisms of the interaction between MSCs and various participants in inflammation. Depending on their type and intensity, inflammatory stimuli confer on MSCs the ability to suppress the immune response in some cases or to enhance it in others. Here we review the current findings on the immunoregulatory plasticity of MSCs in disease pathogenesis and therapy. © 2014 Nature America, Inc. All rights reserved.

Chen Y.,UMDNJ Robert Wood Johnson Medical School | Chen Y.,Washington University in St. Louis | Rabson A.B.,Child Health Institute of New Jersey | Gorski D.H.,Barbara Ann Karmanos Cancer Institute
Cardiovascular Research | Year: 2010

Aims Tumours secrete proangiogenic factors to induce the ingrowth of blood vessels, the end targets of which are vascular endothelial cells (ECs). The MEOX2 homeoprotein inhibits nuclear factor-κB (NF-κB) signalling and EC activation in response to serum and proangiogenic factors. We hypothesize that MEOX2 interacts with components of this pathway in vascular ECs to modulate NF-κB activity and EC activation and that these interactions depend upon specific domains within the MEOX2 protein. Methods and results To test our hypothesis, we transduced ECs with MEOX2 expression constructs. MEOX2 protein localized to the nuclear fraction, as did IκBβ and p65. By co-immunoprecipitation, MEOX2 bound to both p65 and IκBβ. Immunofluorescence demonstrated that MEOX2 colocalizes in the nucleus with both p65 and IκBβ and that this colocalization requires the MEOX2 homeodomain and N-terminal domain. Finally, promoter assays revealed that MEOX2 expression has a biphasic effect on NF-κB-dependent promoters. At low levels, MEOX2 stimulates NF-κB activity, whereas at high levels, it represses, effects that also depend upon the homeodomain and the N-terminal domain. Conclusion Our results represent the first report of an interaction between a homeobox protein and IκBβ and suggest that MEOX2 modulates the activity of the RelA complex through direct interaction with its components. These observations implicate MEOX2 as a potentially important regulatory gene inhibiting not only the angiogenic response of ECs to proangiogenic factors, but also their response to chronic inflammatory stimulation that normally activates NF-κB, suggesting MEOX2 as a possible molecular target for the therapy of angiogenesis-dependent diseases such as cancer. © 2010 The Author.

Chen X.,CAS Shanghai Institutes for Biological Sciences | Gan Y.,CAS Shanghai Institutes for Biological Sciences | Li W.,CAS Shanghai Institutes for Biological Sciences | Su J.,CAS Shanghai Institutes for Biological Sciences | And 7 more authors.
Cell death & disease | Year: 2014

Mesenchymal stem cells (MSCs) are believed to exert their regenerative effects through differentiation and modulation of inflammatory responses. However, the relationship between the severity of inflammation and stem cell-mediated tissue repair has not been formally investigated. In this study, we applied different concentrations of dexamethasone (Dex) to anti-CD3-activated splenocyte cultured with or without MSCs. As expected, Dex exhibited a classical dose-dependent inhibition of T-cell proliferation. Surprisingly, although MSCs also blocked T-cell proliferation, the presence of Dex unexpectedly showed a dose-dependent reversion of T-cell proliferation. This effect of Dex was found to be exerted through interfering STAT1 phosphorylation-prompted expression of inducible nitric oxide synthase (iNOS). Interestingly, inflammation-induced chemokines in MSCs was unaffected. To test the role of inflammation severity in stem cell-mediated tissue repair, we employed mice with carbon tetrachloride-induced advanced liver fibrosis and found that although MSCs alone were effective, concurrent administration of Dex abrogated the therapeutic effects of MSCs on fibrin deposition, serum levels of bilirubin, albumin, and aminotransferases, as well as T-lymphocyte infiltration, especially IFN-γ(+)CD4(+) and IL-17A(+)CD4(+)T cells. Likewise, iNOS(-/-) MSCs, which produce chemokines but not nitric oxide under inflammatory conditions, are ineffective in treating advanced liver fibrosis. Therefore, inflammation has a critical role in MSC-mediated tissue repair. In addition, concomitant application of MSCs with steroids should be avoided.

Osada M.,City College of New York | Singh V.J.,City College of New York | Wu K.,City College of New York | Sant'Angelo D.B.,Child Health Institute of New Jersey | Pezzano M.,City College of New York
PLoS ONE | Year: 2013

Thymic microenvironments are essential for the proper development and selection of T cells critical for a functional and self-tolerant adaptive immune response. While significant turnover occurs, it is unclear whether populations of adult stem cells contribute to the maintenance of postnatal thymic epithelial microenvironments. Here, the slow cycling characteristic of stem cells and their property of label-retention were used to identify a K5-expressing thymic stromal cell population capable of generating clonal cell lines that retain the capacity to differentiate into a number of mesenchymal lineages including adipocytes, chondrocytes and osteoblasts suggesting a mesenchymal stem cell-like phenotype. Using cell surface analysis both culture expanded LRCs and clonal thymic mesenchymal cell lines were found to express Sca1, PDGFRα, PDGFRβ,CD29, CD44, CD49F, and CD90 similar to MSCs. Sorted GFP-expressing stroma, that give rise to TMSC lines, contribute to thymic architecture when reaggregated with fetal stroma and transplanted under the kidney capsule of nude mice. Together these results show that the postnatal thymus contains a population of mesenchymal stem cells that can be maintained in culture and suggests they may contribute to the maintenance of functional thymic microenvironments. Copyright: © 2013 Osada et al.

Anderson S.,Rutgers University | Brooks S.S.,Child Health Institute of New Jersey
Advances in Neonatal Care | Year: 2015

Background: Advanced prenatal screening and diagnostic testing have increased the number of newborns born with a confirmed diagnosis. Not all infants, however, are born with a known diagnosis. In fact, for some conditions, physical findings evolve over time and diagnosis can be further delayed because of premature birth. Purpose: This article shares a case report of a dysmorphic preterm infant admitted to the intensive care nursery for routine care. The emergence of physical findings as the baby matured during the first weeks of life and the stepwise, diagnostic approach used to confirm a rare genetic condition, cardiofaciocutaneous (CFC) syndrome, is provided. Case Findings/Results: Key physical differences apparent at birth prompted screening for several genetic syndromes and a number of inborn errors of metabolism. As the phenotype emerged, a type of RASopathy entered the differential, the most likely of which was CFC syndrome. Implications for Practice: Although CFC syndrome is rare, the combined incidence rate of RASopathies is greater, and as such, providers should be familiar with such conditions. Classic features may not be apparent in preterm infants so providers must remain astute to physical changes and communicate them with genetic consultants. Implications for Research: Gaining a better understanding of how providers can best support parents through the lengthy, diagnostic odyssey of genetic testing is important. In addition, ongoing research is needed to try to identify a genotype-phenotype correlation for CFC syndrome to guide patient surveillance and provide prognostic information to parents. Copyright © 2015 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.

Lynch L.,Harvard University | Michelet X.,Harvard University | Zhang S.,Rutgers Robert Wood Johnson Medical School | Brennan P.J.,Harvard University | And 12 more authors.
Nature Immunology | Year: 2015

Invariant natural killer T cells (iNKT cells) are lipid-sensing innate T cells that are restricted by the antigen-presenting molecule CD1d and express the transcription factor PLZF. iNKT cells accumulate in adipose tissue, where they are anti-inflammatory, but the factors that contribute to their anti-inflammatory nature, as well as their targets in adipose tissue, are unknown. Here we found that iNKT cells in adipose tissue had a unique transcriptional program and produced interleukin 2 (IL-2) and IL-10. Unlike other iNKT cells, they lacked PLZF but expressed the transcription factor E4BP4, which controlled their IL-10 production. The adipose iNKT cells were a tissue-resident population that induced an anti-inflammatory phenotype in macrophages and, through the production of IL-2, controlled the number, proliferation and suppressor function of regulatory T cells (T reg cells) in adipose tissue. Thus, iNKT cells in adipose tissue are unique regulators of immunological homeostasis in this tissue. © 2015 Nature America, Inc.

Noonan K.,Rider University | Corman H.,Rider University | Schwartz-Soicher O.,Columbia University | Reichman N.E.,Child Health Institute of New Jersey
Maternal and Child Health Journal | Year: 2013

The broad goal of contemporary prenatal care is to promote the health of the mother, child, and family through the pregnancy, delivery, and the child's development. Although the vast majority of mothers giving birth in developed countries receive prenatal care, past research has not found compelling evidence that early or adequate prenatal care has favorable effects on birth outcomes. It is possible that prenatal care confers health benefits to the child that do not become apparent until after the perinatal period. Using data from a national urban birth cohort study in the US, we estimate the effects of prenatal care on four markers of child health at age 5 - maternal-reported health status, asthma diagnosis, overweight, and height. Prenatal care, defined a number of different ways, does not appear to have any effect on the outcomes examined. The findings are robust and suggest that routine health care encounters during the prenatal period could potentially be used more effectively to enhance children's health trajectories. However, future research is needed to explore the effects of prenatal care on additional child health and developmental outcomes as well as the effects of preconceptional and maternal lifetime healthcare on child health. © 2012 Springer Science+Business Media, LLC.

Citri A.,Stanford University | Pang Z.P.,Stanford University | Pang Z.P.,Child Health Institute of New Jersey | Sudhof T.C.,Stanford University | And 3 more authors.
Nature Protocols | Year: 2012

A major challenge in neuronal stem cell biology lies in characterization of lineage-specific reprogrammed human neuronal cells, a process that necessitates the use of an assay sensitive to the single-cell level. Ssingle-cell gene profiling can provide definitive evidence regarding the conversion of one cell type into another at a high level of resolution. The protocol we describe uses Fluidigm Biomark dynamic arrays for high-throughput expression profiling from single neuronal cells, assaying up to 96 independent samples with up to 96 quantitative PCRpcr (qPCRpcr) probes (equivalent to 9,216 reactions) in a single experiment, which can be completed within 2-3 d. protocol enables simple and cost-effective profiling of several hundred transcripts from a single cell, and it could have numerous utilities. © 2012 Nature America, Inc. All rights reserved.

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