EOH Events

EOH Departmental Calendar

Event
Thu 10/24/2019 11:00AM - 12:00PM
EOH Journal Club
Maternal vitamin C regulates reprogramming of DNA methylation and germline development EOH Journal Club
Maternal vitamin C regulates reprogramming of DNA methylation and germline development
Thu 10/24/2019 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Qi Wei

Paper: Maternal vitamin C regulates reprogramming of DNA methylation and germline development

Authors: Stephanie P. Ditroia, Michelle Percharde, Marie-Justine Guerquin, estelle Wall, evelyne Collignon, Kevin t. ebata, Kathryn Mesh, Swetha Mahesula, Michalis Agathocleous, Diana J. Laird, Gabriel Livera & Miguel Ramalho-Santos

Abstract: Development is often assumed to be hardwired in the genome, but several lines of evidence indicate that it is susceptible to environmental modulation with potential long-term consequences, including in mammals1,2. The embryonic germline is of particular interest because of the potential for intergenerational epigenetic effects. The mammalian germline undergoes extensive DNA demethylation3–7 that occurs in large part by passive dilution of methylation over successive cell divisions, accompanied by active DNA demethylation by TET enzymes3,8–10. TET activity has been shown to be modulated by nutrients and metabolites, such as vitamin C11–15. Here we show that maternal vitamin C is required for proper DNA demethylation and the development of female fetal germ cells in a mouse model. Maternal vitamin C deficiency does not affect overall embryonic development but leads to reduced numbers of germ cells, delayed meiosis and reduced fecundity in adult offspring. The transcriptome of germ cells from vitamin-C-deficient
 embryos is remarkably similar to that of embryos carrying a null mutation in Tet1. Vitamin C deficiency leads to an aberrant DNA methylation profile that includes incomplete demethylation of key regulators of meiosis and transposable elements. These findings reveal that deficiency in vitamin C during gestation partially recapitulates loss of TET1, and provide a potential intergenerational mechanism for adjusting fecundity to environmental conditions


4140 Public Health, Young Seminar Room
Thu 10/31/2019 11:00AM - 12:00PM
EOH Journal Club
Electronic cigarettes disrupt lung lipid homeostasis and innate immunity independent of nicotine EOH Journal Club
Electronic cigarettes disrupt lung lipid homeostasis and innate immunity independent of nicotine
Thu 10/31/2019 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Emily Nicholls

Paper: Electronic cigarettes disrupt lung lipid homeostasis and innate immunity independent of nicotine

Authors: Matthew C. Madison, … , David B. Corry, Farrah Kheradmand

Abstract: Electronic nicotine delivery systems (ENDS) or e-cigarettes have emerged as a popular recreational tool among adolescents and adults. Although the use of ENDS is often promoted as a safer alternative to conventional cigarettes, few comprehensive studies have assessed the long-term effects of vaporized nicotine and its associated solvents, propylene glycol (PG) and vegetable glycerin (VG). Here, we show that compared with smoke exposure, mice receiving ENDS vapor for 4 months failed to develop pulmonary inflammation or emphysema. However, ENDS exposure, independent of nicotine, altered lung lipid homeostasis in alveolar macrophages and epithelial cells. Comprehensive lipidomic and structural analyses of the lungs revealed aberrant phospholipids in alveolar macrophages and increased surfactant-associated phospholipids in the airway. In addition to ENDS-induced lipid deposition, chronic ENDS vapor exposure downregulated innate immunity against viral pathogens in resident macrophages. Moreover, independent of nicotine, ENDS-exposed mice infected with influenza demonstrated enhanced lung inflammation and tissue damage. Together, our findings reveal that chronic e-cigarette vapor aberrantly alters the physiology of lung epithelial cells and resident immune cells and promotes poor response to infectious challenge. Notably, alterations in lipid homeostasis and immune impairment are independent of nicotine, thereby warranting more extensive investigations of the vehicle solvents used in e-cigarettes.


4140 Public Health, Young Seminar Room
Fri 11/1/2019 1:00PM - 2:00PM
EOH Seminar Series
Environment/diet interaction in fatty liver diseases EOH Seminar Series
Environment/diet interaction in fatty liver diseases
Fri 11/1/2019 1:00PM - 2:00PM
A719 Public Health


A719 Public Health
Thu 11/7/2019 11:00AM - 12:00PM
EOH Journal Club
TREM2 Acts Downstream of CD33 in Modulating Microglial Pathology in Alzheimer’s Disease EOH Journal Club
TREM2 Acts Downstream of CD33 in Modulating Microglial Pathology in Alzheimer’s Disease
Thu 11/7/2019 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Yi Lu

Paper: TREM2 Acts Downstream of CD33 in Modulating Microglial Pathology in Alzheimer’s Disease

Authors: Ana Griciuc, Shaun Patel, Anthony N. Federico, ..., Joseph El Khoury, Marco Colonna, Rudolph E. Tanzi

Abstract: The microglial receptors CD33 and TREM2 have been associated with risk for Alzheimer’s disease (AD). Here, we investigated crosstalk between CD33 and TREM2. We showed that knockout of CD33 attenu-ated amyloid beta (Ab) pathology and improved cognition in 5xFAD mice, both of which were abro-gated by additional TREM2 knockout. Knocking out TREM2 in 5xFAD mice exacerbated Ab pathology and neurodegeneration but reduced Iba1+ cell numbers, all of which could not be rescued by addi-tional CD33 knockout. RNA-seq profiling of microglia revealed that genes related to phagocytosis and signaling (IL-6, IL-8, acute phase response) are upre-gulated in 5xFAD;CD33 and downregulated in 5xFAD;TREM2 mice. Differential gene expression in 5xFAD;CD33 microglia depended on the pres-ence of TREM2, suggesting TREM2 acts downstream of CD33. Crosstalk between CD33 and TREM2 in-cludes regulation of the IL-1b/IL-1RN axis and a gene set in the ‘‘receptor activity chemokine’’ cluster. Our results should facilitate AD therapeutics target-ing these receptors.


4140 Public Health, Young Seminar Room
Thu 11/14/2019 11:00AM - 12:00PM
EOH Journal Club
Effects of Perfluorooctanoic Acid on Metabolic Profiles in Brain and Liver EOH Journal Club
Effects of Perfluorooctanoic Acid on Metabolic Profiles in Brain and Liver
Thu 11/14/2019 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Jenna Kuhn

Paper: Effects of Perfluorooctanoic Acid on Metabolic Profiles in Brain and Liver of Mouse Revealed by a Highthroughput Targeted Metabolomics Approach

Authors: Nanyang Yu, Si Wei, Meiying Li, Jingping Yang, Kan Li, Ling Jin, Yuwei Xie, John P. Giesy, Xiaowei Zhang & Hongxia Yu

Abstract:
Perfluorooctanoic acid (PFOA), a perfluoroalkyl acid, can result in hepatotoxicity and neurobehavioral effects in animals. The metabolome, which serves as a connection among transcriptome, proteome and toxic effects, provides pathway-based insights into effects of PFOA. Since understanding of changes in the metabolic profile during hepatotoxicity and neurotoxicity were still incomplete, a high-throughput targeted metabolomics approach (278 metabolites) was used to investigate effects of exposure to PFOA for 28 d on brain and liver of male Balb/c mice. Results of multivariate statistical analysis indicated that PFOA caused alterations in metabolic pathways in exposed individuals. Pathway analysis suggested that PFOA affected metabolism of amino acids, lipids, carbohydrates and energetics. Ten and 18 metabolites were identified as potential unique biomarkers of exposure to PFOA in brain and liver, respectively. In brain, PFOA affected concentrations of neurotransmitters, including serotonin, dopamine, norepinephrine, and glutamate in brain, which provides novel insights into mechanisms of PFOA-induced neurobehavioral effects. In liver, profiles of lipids revealed involvement of β-oxidation and biosynthesis of saturated and unsaturated fatty acids in PFOA-induced hepatotoxicity, while alterations in metabolism of arachidonic acid suggesting potential of PFOA to cause inflammation response in liver. These results provide insight into the mechanism and biomarkers for PFOA-induced effects.


4140 Public Health, Young Seminar Room
Fri 11/15/2019 1:00PM - 2:00PM
EOH Seminar Series
Public access to environ health data in Pennsylvania: What are the gaps? What is readily available? EOH Seminar Series
Public access to environ health data in Pennsylvania: What are the gaps? What is readily available?
Fri 11/15/2019 1:00PM - 2:00PM
A719 Public Health


A719 Public Health
Thu 11/21/2019 11:00AM - 12:00PM
EOH Journal Club
Association of Environmental Toxins With Amyotrophic Lateral Sclerosis EOH Journal Club
Association of Environmental Toxins With Amyotrophic Lateral Sclerosis
Thu 11/21/2019 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Fan Wu

Paper: Association of Environmental Toxins With Amyotrophic Lateral Sclerosis

Authors: Feng-Chiao Su,PhD; Stephen A. Goutman,MD; Sergey Chernyak,PhD; Bhramar Mukherjee,PhD; Brian C. Callaghan,MD; Stuart Batterman,PhD; Eva L. Feldman,MD,PhD

Abstract:
IMPORTANCE
Persistent environmental pollutants may represent a modifiable risk factor involved in the gene-time-environment hypothesis in amyotrophic lateral sclerosis (ALS).

OBJECTIVE
To evaluate the association of occupational exposures and environmental toxins on the odds of developing ALS in Michigan.

DESIGN, SETTING, AND PARTICIPANTS
Case-control study conducted between 2011 and 2014
at a tertiary referral center for ALS. Cases were patients diagnosed as having definitive,
probable, probable with laboratory support, or possible ALS by revised El Escorial criteria;
controls were excluded if they were diagnosed as having ALS or another neurodegenerative
condition or if they had a family history of ALS in a first- or second-degree blood relative.
Participants completed a survey assessing occupational and residential exposures. Blood
concentrations of 122 persistent environmental pollutants, including organochlorine
pesticides (OCPs), polychlorinated biphenyls (PCBs), and brominated flame retardants
(BFRs), were measured using gas chromatography–mass spectrometry. Multivariable models
with self-reported occupational exposures in various exposure time windows and
environmental toxin blood concentrations were separately fit by logistic regression models.
Concordance between the survey data and pollutant measurements was assessed using the
nonparametric Kendall τ correlation coefficient.

MAIN OUTCOMES AND MEASURES
Occupational and residential exposures to environmental toxins, and blood concentrations of 122 persistent environmental pollutants, including OCPs,
PCBs, and BFRs.

RESULTS
Participants included 156 cases (mean [SD] age, 60.5 [11.1] years; 61.5%male) and 128 controls (mean [SD] age, 60.4 [9.4] years; 57.8%male); among them, 101 cases and 110 controls had complete demographic and pollutant data. Survey data revealed that reported
pesticide exposure in the cumulative exposure windows was significantly associated with ALS
(odds ratio [OR] = 5.09; 95%CI, 1.85-13.99; P = .002). Military service was also associated
with ALS in 2 time windows (exposure ever happened in entire occupational history:
OR = 2.31; 95%CI, 1.02-5.25; P = .046; exposure ever happened 10-30 years ago: OR = 2.18;
95%CI, 1.01-4.73; P = .049). A multivariable model of measured persistent environmental
pollutants in the blood, representing cumulative occupational and residential exposure,
showed increased odds of ALS for 2 OCPs (pentachlorobenzene: OR = 2.57; 95%CI, 1.31-5.02;
P = .006; and cis-chlordane: OR = 6.51; 95%CI, 2.05-20.73; P = .002) and 1 PCB (PCB 151:
OR = 1.66; 95%CI, 1.03-2.67; P = .04. There was modest concordance between survey data
and the measurements of persistent environmental pollutants in blood; significant Kendall τ
correlation coefficients ranged from −0.18 (Dacthal and “use pesticides to treat home or
yard”) to 0.24 (trans-nonachlor and “store lawn care products in garage”).

CONCLUSIONS AND RELEVANCE
In this study, persistent environmental pollutants measured in blood were significantly associated with ALS and may represent modifiable ALS disease risk
factors.


4140 Public Health, Young Seminar Room
Thu 12/5/2019 11:00AM - 12:00PM
EOH Journal Club
Protein Arginine Methyltransferase 4 (PRMT4) mediates lymphopenia in experimental sepsis EOH Journal Club
Protein Arginine Methyltransferase 4 (PRMT4) mediates lymphopenia in experimental sepsis
Thu 12/5/2019 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Rushikesh Deshpande

Paper: Protein Arginine Methyltransferase 4 (PRMT4) mediates lymphopenia in experimental sepsis

Authors: Yandong Lai, Xiuying Li, Tiao Li, Yan Chen, Chen Long, Toru Nyunoya, Kong Chen,Georgios D. Kitsios,Seyed Mehdi Nouraie,Yingze Zhang, Bryan J. McVerry, Janet S. Lee,Rama K. Mallampalli, and Chunbin Zou

Abstract:
Onehallmark of sepsis is a reduced number of lymphocytes, termed lymphopenia,that occurs from decreased lymphocyte proliferation or increased cell death contributing to immune suppression. Histone modification enzymes regulate immunity by epigenetically modulating chromatin architecture, however, the role of these enzymes in lymphopenia remains elusive. In this study, we identified that a chromatin modulator Protein Arginine N-methyltransferase 4/Coactivator-Associated Arginine Methyltransferase 1 (PRMT4/ CARM1) that is elevated systemically inseptic patients and experimental sepsis, and is crucialfor inducing T-lymphocyte apoptosis.An E3 ubiquitin ligase SCFFBXO9 docks on PRMT4 via a phosphodegron to ubiquitinate the protein at K228 for ubiquitin proteasomal degradation.  High PRMT4 expression resulted from reduced levels of SCFFBXO9 that led to increased lymphocyte cell death after Escherichia coliorlipopolysaccharide(LPS) exposure. Ectopic expression of PRMT4 protein caused substantially mphocytedeathvia caspase 3 mediated cell death signaling, and knockout of PRMT4 abolished LPS mediated lymphocyte cell death. PRMT4 inhibition with a small molecule compound attenuated lymphocyte death in complementary models of sepsis. These findings demonstrate a previously uncharacterized role of a key chromatin modulator in lymphocytesurvival that may shed light on devising unique therapeutic modalities to lessen severity of septic immunosuppression.


4140 Public Health, Young Seminar Room

Recent Events

EOH Journal Club

EOH Journal Club Seminar

Thursday 1/14 11:00AM - 12:00PM

339 Bridgeside Point

Teresa Anguiano will present on the article - "Intravital Imaging Reveals Ghost Fibers as Architectural Units Guiding Myogenic Progenitors during Regeneration"

 

 

 

 

 

 

 

 

 

EOH Journal Club Seminar - Spring 2016 Date: Thursday January 14, 2016 Time: 11am - 12pm Presenter: Teresa Anguiano Paper: Intravital Imaging Reveals Ghost Fibers as Architectural Units Guiding Myogenic Progenitors during Regeneration Authors: Micah T. Webster, Uri Manor, Jennifer Lippincott-Schwartz, Chen-Ming Fan Abstract: How resident stem cells and their immediate progenitors rebuild tissues of pre-injury organization and size for proportional regeneration is not well understood. Using 3D, time-lapse intravital imaging for direct visualization of the muscle regeneration process in live mice, we report that extracellular matrix remnants from injured skeletal muscle fibers, ‘‘ghost fibers,’’ govern muscle stem/progenitor cell behaviors during proportional regeneration. Stem cells were immobile and quiescent without injury whereas their activated progenitors migrated and divided after injury. Unexpectedly, divisions and migration were primarily bi-directionally oriented along the ghost fiber longitudinal axis, allowing for spreading of progenitors throughout ghost fibers. Re-orienting ghost fibers impacted myogenic progenitors’ migratory paths and division planes, causing disorganization of regenerated muscle fibers. We conclude that ghost fibers are autonomous, architectural units necessary for proportional regeneration after tissue injury. This finding reinforces the need to fabricate bioengineered matrices that mimic living tissue matrices for tissue regeneration therapy.

Last Updated On Monday, March 21, 2016 by GSPH Webmaster
Created On Monday, March 21, 2016

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