EOH Events

EOH Departmental Calendar

Event
Thu 2/20/2020 11:00AM - 12:00PM
EOH Journal Club
Mitochondrial oxidants, but not respiration, are sensitive to glucose in adipocytes EOH Journal Club
Mitochondrial oxidants, but not respiration, are sensitive to glucose in adipocytes
Thu 2/20/2020 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Heng Bai

Paper: Mitochondrial oxidants, but not respiration, are sensitive to
glucose in adipocytes

Authors: James R. Krycer, Sarah D. Elkington, Alexis Diaz-Vegas, Kristen C. Cooke, James G. Burchfield, Kelsey H. Fisher-Wellman, Gregory J. Cooney, Daniel J. Fazakerley, and David E. James

Abstract:
Insulin action in adipose tissue is crucial for whole-body glucose homeostasis, with insulin resistance being a major risk factor for metabolic diseases such as type 2 diabetes. Recent studies have proposed mitochondrial oxidants as a unifying driver of adipose insulin resistance, serving as a signal of nutrient excess. However, neither the substrates for nor sites of oxidant production are known. Because insulin stimulates glucose utilization, we hypothesized that glucose oxidation would fuel respiration, in turn generating mitochondrial oxidants. This would impair insulin action, limiting further glucose uptake in a negative feedback loop of “glucose-dependent” insulin resistance. Using primary rat adipocytes and cultured 3T3-L1 adipocytes, we observed that insulin increased respiration, but notably this occurred independently of glucose supply. In contrast, glucose was required for insulin to increase mitochondrial oxidants. Despite rising to similar levels as when treated with other agents that cause insulin resistance, glucose-dependent mitochondrial oxidants failed to cause insulin resistance. Subsequent studies revealed a temporal relationship whereby mitochondrial oxidants needed to increase before the insulin stimulus to induce insulin resistance. Together, these data reveal that (a) adipocyte respiration is principally fueled from nonglucose sources; (b) there is a disconnect between respiration and oxidative stress, whereby mitochondrial oxidant levels do not rise with increased respiration unless glucose is present; and (c) mitochondrial oxidative stress must precede the insulin stimulus to cause insulin


4140 Public Health, Young Seminar Room
Thu 2/27/2020 11:00AM - 12:00PM
EOH Journal Club
VISTA is a checkpoint regulator for naïve T cell quiescence and peripheral tolerance EOH Journal Club
VISTA is a checkpoint regulator for naïve T cell quiescence and peripheral tolerance
Thu 2/27/2020 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Qi Wei

Paper: VISTA is a checkpoint regulator for naïve T cell quiescence and peripheral tolerance

Authors: Mohamed A. ElTanbouly, Yanding Zhao, Elizabeth Nowak, Jiannan Li, Evelien Schaafsma, et Al.

Abstract:
Negative checkpoint regulators (NCRs) temper the T cell immune response to self-antigens and limit the development of autoimmunity. Unlike all other NCRs that are expressed on activated T lymphocytes, V-type immunoglobulin domain-containing suppressor of T cell activation (VISTA) is expressed on naïve T cells. We report an unexpected heterogeneity within the naïve T cell compartment in mice, where loss of VISTA disrupted the major quiescent naïve T cell subset and enhanced self-reactivity. Agonistic VISTA engagement increased T cell tolerance by promoting antigen-induced peripheral T cell deletion. Although a critical player in naïve T cell homeostasis, the ability of VISTA to restrain naïve T cell responses was lost under inflammatory conditions. VISTA is therefore a distinctive NCR of naïve T cells that is critical for steady-state maintenance of quiescence and peripheral tolerance.


4140 Public Health, Young Seminar Room
Thu 3/5/2020 11:00AM - 12:00PM
EOH Journal Club
Impacts of climate change on future air quality and human health in China EOH Journal Club
Impacts of climate change on future air quality and human health in China
Thu 3/5/2020 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Emily Nicholls

Paper:     Impacts of climate change on future air quality and human health in China

Authors: Chaopeng Hong, Qiang Zhang, Yang Zhang, Steven J. Davis, Dan Tong, Yixuan Zheng, Zhu Liu, Dabo Guan,
Kebin He, and Hans Joachim Schellnhuber

Abstract:
In recent years, air pollution has caused more than 1 million deaths per year in China, making it a major focus of public health efforts. However, future climate change may exacerbate such human health impacts by increasing the frequency and duration of weather conditions that enhance air pollution exposure. Here, we use a combination of climate, air quality, and epidemiological models to assess future air pollution deaths in a changing climate under Representative Concentration Pathway 4.5 (RCP4.5). We find that, assuming pollution emissions and population are held constant at current levels, climate change would adversely affect future air quality for >85% of China’s population (∼55% of land area) by the middle of the century, and would increase by 3% and 4% the population-weighted average concentrations of fine particulate matter (PM2.5) and ozone, respectively. As a result, we estimate an additional 12,100 and 8,900 Chinese (95% confidence interval: 10,300 to 13,800 and 2,300 to 14,700, respectively) will die per year from PM2.5 and ozone exposure, respectively. The important underlying climate mechanisms are changes in extreme conditions such as atmospheric stagnation and heat waves (contributing 39% and 6%, respectively, to the increase in mortality). Additionally, greater vulnerability of China’s aging population will further increase the estimated deaths from PM2.5 and ozone in 2050 by factors of 1 and 3, respectively. Our results indicate that climate change and more intense extremes are likely to increase the risk of severe pollution events in China. Managing air quality in China in a changing climate will thus become more challenging.


4140 Public Health, Young Seminar Room
Fri 3/6/2020 1:00PM - 3:00PM
EOH Dissertation Defense
Travis Lear - Ubiquitin E3 Ligases in Lung Diseases EOH Dissertation Defense
Travis Lear - Ubiquitin E3 Ligases in Lung Diseases
Fri 3/6/2020 1:00PM - 3:00PM
1155 Public Health, Foster Conf. Rm. (former 1149)


1155 Public Health, Foster Conf. Rm. (former 1149)
Thu 3/19/2020 11:00AM - 12:00PM
EOH Journal Club
Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular EOH Journal Club
Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular
Thu 3/19/2020 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Yi Lu

Paper: Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease

Authors: Yingyue Zhou, Wilbur M. Song, Prabhakar S. Andhey, et Al.

Abstract:
Glia have been implicated in Alzheimer’s disease (AD) pathogenesis. Variants of the microglia receptor triggering receptor expressed on myeloid cells 2 (TREM2) increase AD risk, and activation of disease-associated microglia (DAM) is dependent on TREM2 in mouse models of AD. We surveyed gene-expression changes associated with AD pathology and TREM2 in 5XFAD mice and in human AD by single-nucleus RNA sequencing. We confirmed the presence of Trem2-dependent DAM and identified a previously undiscovered Serpina3n+C4b+ reactive oligodendrocyte population in mice. Interestingly, remarkably differential phenotypes were evident in human AD. Microglia signature was reminiscent of IRF8-driven reactive microglia in peripheral- nerve injury. Oligodendrocyte signatures suggested impaired axonal myelination and metabolic adaptation to neuronal degeneration. Astrocyte profiles indicated weakened metabolic coordination with neurons. Notably, the reactive phenotype of microglia was less evident in TREM2-R47H and TREM2-R62H carriers than in non-carriers,


4140 Public Health, Young Seminar Room
Thu 3/26/2020 11:00AM - 12:00PM
EOH Journal Club
Organophosphorus pesticide chlorpyrifos intake promotes obesity and insulin resistance through impac EOH Journal Club
Organophosphorus pesticide chlorpyrifos intake promotes obesity and insulin resistance through impac
Thu 3/26/2020 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Jenna Kuhn

Paper: Organophosphorus pesticide chlorpyrifos intake promotes obesity and insulin resistance through impacting gut and gut microbiota

Authors: Yiran Liang, Jing Zhan, Donghui Liu, Mai Luo, Jiajun Han, Xueke Liu, Chang Liu, Zheng Cheng, Zhiqiang Zhou, and Peng Wang

Abstract:
Background
Disruption of the gut microbiota homeostasis may induce low-grade inflammation leading to obesity-associated diseases. A major protective mechanism is to use the multi-layered mucus structures to keep a safe distance between gut epithelial cells and microbiota. To investigate whether pesticides would induce insulin resistance/obesity through interfering with mucus-bacterial interactions, we conducted a study to determine how long-term exposure to chlorpyrifos affected C57Bl/6 and CD-1 (ICR) mice fed high- or normal-fat diets. To further investigate the effects of chlorpyrifos-altered microbiota, antibiotic treatment and microbiota transplantation experiments were conducted.

Results
The results showed that chlorpyrifos caused broken integrity of the gut barrier, leading to increased lipopolysaccharide entry into the body and finally low-grade inflammation, while genetic background and diet pattern have limited influence on the chlorpyrifos-induced results. Moreover, the mice given chlorpyrifos-altered microbiota had gained more fat and lower insulin sensitivity.

Conclusions
Our results suggest that widespread use of pesticides may contribute to the worldwide epidemic of inflammation-related diseases.


4140 Public Health, Young Seminar Room
Thu 4/2/2020 11:00AM - 12:00PM
EOH Journal Club
M2 polarization of macrophages facilitates arsenic-induced cell transformation of lung epithelial ce EOH Journal Club
M2 polarization of macrophages facilitates arsenic-induced cell transformation of lung epithelial ce
Thu 4/2/2020 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Grace Ge

Paper: M2 polarization of macrophages facilitates arsenic-induced cell transformation of lung epithelial cells

Authors:  Jiajun Cui, Wenhua Xu, Jian Chen, Hui Li, Lu Dai, Jacqueline A. Frank,Shaojun Peng, Siying Wang, Gang Chen

Abstract: The alterations in microenvironment upon chronic arsenic exposure may
contribute to arsenic-induced lung carcinogenesis. Immune cells, such as
macrophages, play an important role in mediating the microenvironment in the lungs.
Macrophages carry out their functions after activation. There are two activation status
for macrophages: classical (M1) or alternative (M2); the latter is associated with
tumorigenesis. Our previous work showed that long-term arsenic exposure induces
transformation of lung epithelial cells. However, the crosstalk between epithelial cells
and macrophages upon arsenic exposure has not been investigated. In this study,
using a co-culture system in which human lung epithelial cells are cultured with
macrophages, we determined that long-term arsenic exposure polarizes macrophages
towards M2 status through ROS generation. Co-culture with epithelial cells further
enhanced the polarization of macrophages as well as transformation of epithelial cells,
while blocking macrophage M2 polarization decreased the transformation. In addition,
macrophage M2 polarization decreased autophagy activity, which may account for
increased cell transformation of epithelial cells with co-culture of macrophages.


4140 Public Health, Young Seminar Room
Thu 4/9/2020 11:00AM - 12:00PM
EOH Journal Club
Pseudomonas aeruginosa utilizes host polyunsaturated phosphatidylethanolamines to trigger theft-ferr EOH Journal Club
Pseudomonas aeruginosa utilizes host polyunsaturated phosphatidylethanolamines to trigger theft-ferr
Thu 4/9/2020 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Rushikesh Deshpande

Paper: Pseudomonas aeruginosa utilizes host polyunsaturated phosphatidylethanolamines to trigger theft-ferroptosis in bronchial epithelium

Authors: Haider H. Dar, … , Hülya Bayır, Valerian E. Kagan

Abstract:
Ferroptosis is a death program executed via selective oxidation of arachidonic acid–
phosphatidylethanolamines (AA-PE) by 15-lipoxygenases. In mammalian cells and tissues,
ferroptosis has been pathogenically associated with brain, kidney, and liver injury/diseases.
We discovered that a prokaryotic bacterium, Pseudomonas aeruginosa, that does not
contain AA-PE can express lipoxygenase (pLoxA), oxidize host AA-PE to 15-hydroperoxy-
AA-PE (15-HOO-AA-PE), and trigger ferroptosis in human bronchial epithelial cells.
Induction of ferroptosis by clinical P. aeruginosa isolates from patients with persistent lower
respiratory tract infections was dependent on the level and enzymatic activity of pLoxA.
Redox phospholipidomics revealed elevated levels of oxidized AA-PE in airway tissues
from patients with cystic fibrosis (CF) but not with emphysema or CF without P. aeruginosa.
We believe that the evolutionarily conserved mechanism of pLoxA-driven ferroptosis may
represent a potential therapeutic target against P. aeruginosa–associated diseases such as
CF and persistent lower respiratory tract infections.


4140 Public Health, Young Seminar Room
Thu 4/16/2020 11:00AM - 12:00PM
EOH Journal Club
Rap1 regulates hematopoietic stem cell survival and affects oncogenesis and response to chemotherapy EOH Journal Club
Rap1 regulates hematopoietic stem cell survival and affects oncogenesis and response to chemotherapy
Thu 4/16/2020 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Pattra Chun-On

Paper: Rap1 regulates hematopoietic stem cell survival and affects oncogenesis and response to chemotherapy

Authors:  Ekta Khattar, Kyaw Ze Ya Maung, Chen Li Chew, et Al.

Abstract: Increased levels and non-telomeric roles have been reported for shelterin proteins, including RAP1 in cancers. Herein using Rap1 null mice, we provide the genetic evidence that mammalian Rap1 plays a major role in hematopoietic stem cell survival, oncogenesis and response
to chemotherapy. Strikingly, this function of RAP1 is independent of its association with the
telomere or with its known partner TRF2. We show that RAP1 interacts with many members
of the DNA damage response (DDR) pathway. RAP1 depleted cells show reduced interaction
between XRCC4/DNA Ligase IV and DNA-PK, and are impaired in DNA Ligase IV recruitment
to damaged chromatin for efficient repair. Consistent with its role in DNA damage repair, RAP1 loss decreases double-strand break repair via NHEJ in vivo, and consequently reduces B cell class switch recombination. Finally, we discover that RAP1 levels are predictive of the success of chemotherapy in breast and colon cancer.


4140 Public Health, Young Seminar Room

Recent Events

EOH Journal Club

Muscle-generated BDNF is a sexually dimorphic myokine that controls metabolic flexibility

Thursday 10/17 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Heng Bai

Paper: Muscle-generated BDNF is a sexually dimorphic myokine that controls metabolic flexibility

Authors: Xiuying Yang, Daniel Brobst, Wing Suen Chan, Margaret Chui Ling Tse,  Oana Herlea-Pana, Palak Ahuja, Et. Al.

Abstract: The ability of skeletal muscle to switch between lipid and glucose oxidation for ATP production during metabolic stress is pivotal for maintaining systemic energy homeostasis, and dysregulation of this metabolic flexibility is a dominant cause of several metabolic disorders. However, the molecular mechanism that governs fuel selection in muscle is not well understood. Here, we report that brain-derived neurotrophic factor (BDNF) is a fasting-induced myokine that controls metabolic reprograming through the AMPK/CREB/PGC-1 pathway in female mice. Female mice with a muscle-specific deficiency in BDNF (MBKO mice) were unable to switch the predominant fuel source from carbohydrates to fatty acids during fasting, which reduced ATP production in muscle. Fasting-induced muscle atrophy was also compromised in female MBKO mice, likely a result of autophagy inhibition. These mutant mice displayed myofiber necrosis, weaker muscle strength, reduced locomotion, and muscle-specific insulin resistance. Together, our results show that muscle-derived BDNF facilitates metabolic adaption during nutrient scarcity in a gender-specific manner and that insufficient BDNF production in skeletal muscle promotes the development of metabolic myopathies and insulin resistance

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Last Updated On Friday, September 20, 2019 by Orbell, Adam W
Created On Friday, September 20, 2019

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