Date and Time: Tuesday, November 6, 2018 12:00 at PM Eastern Time
Title: Targeting Phospholipase D4 Attenuates Kidney Fibrosis
The Molecular and Systems Biology Specialty Section Executive Committee invites you to join a webinar highlighting the research conducted by our 2018 Paper of the Year Award recipient, Dr. Priyanka Trivedi (Harvard Medical School) and 2018 Postdoctoral Fellow Research Award recipient, Dr. Samantha Faber (University of North Carolina, Chapel Hill).
Dr. Trivedi will present her paper titled, “Targeting Phospholipase D4 Attenuates Kidney Fibrosis” (DOI: 10.1681/ASN.2016111222), which was published in the Journal of the American Society of Nephrology in December 2017. She will discuss phospholipase D4 (PLD4), a single-pass transmembrane glycoprotein, which is among the most highly upregulated genes in kidneys with chronic progressive fibrosis.
Dr. Faber will discuss the development and characterization of a novel three-dimensional organotypic airway model. Studies focused on examining key signaling pathways within airway fibroblasts following trans-epithelial air pollutant exposure will also be discussed.
These two presentations will highlight the exceptional research being conducted by young investigators in the Molecular and Systems Biology Specialty Section.
The webinar will begin at 12:00 PM EST on Tuesday, November 6th, 2018 and is free to all attendees.
Date and Time: Monday, November 19, 2018 at 12:00 noon EST
Title: MSBSS Award Webinar Series: 2018 Graduate Student Awards
The Molecular and Systems Biology Specialty Section will be highlighting the research conducted by our 2018 Graduate Student Research Award recipients, Julia Tobacyk (1st place, University of Arkansas), Abhishek Venkatratnam (2nd place, University of North Carolina), and Prarthana Shankar (3rd place, Oregon State University). This webinar will be held on Monday, November 19, 2018 at 12:00 noon EST.
Registration is Required
These three presentations will highlight the exceptional research being conducted by MSBSS graduate students exploring the roles of miRNAs as biomarkers of renal injury, the hepatic transcriptomic response to trichloroethylene, and the role of long non-coding RNA is the regulation of transcription factor sox9b in the toxic response to TCDD. Individual talk abstracts are below.
Julia Tobacyk (University of Arkansas)
Title: Mouse Population-Based Evaluation of Urinary Protein and miRNA Biomarker Performance Associated with Cisplatin Renal Injury
Drug-induced nephrotoxicity plays a major role in the high incidence and prevalence of acute kidney injury (AKI) in in patients. A primary objective of research has been identifying early and reliable biomarkers for detecting AKI in the clinic. Traditional serum markers for assessing renal toxicity, such as creatinine (sCre) and blood urea nitrogen (BUN) are considered insensitive and unable to detect very early stages of kidney injury. However, urinary biomarkers have recently attracted attention as potential biomarkers for early AKI detection. The majority of biomarker discovery experiments have been performed using genetically homogenous rodent models which are limited in their ability to represent natural human variation, therefore may have limited clinical utility. In this study, genetically heterogeneous Diversity Outbred (DO) mice were used as a surrogate for human patients to investigate performance of urinary candidate biomarkers against classical serum biomarkers (BUN and sCre) for AKI. In this study, cisplatin was used as a prototypical kidney toxicant and female adult DO mice were exposed to cisplatin (5 mg/kg, i.p.) or vehicle and necropsied 72 h post-dose and 18 h following overnight urine collection (N=45/group). Interindividual variability in kidney toxicity was observed, with treated DO mice experiencing either no renal tubular cell necrosis (41%), minimal (grade 1, 39%), or mild (grade 2, 20%) necrosis. While there were significant increases in urinary biomarkers with grade 2 necrosis (B2-microglobulin, renin, KIM-1, IP-10, NGAL, osteopontin; miRNA (miR)-138, miR-218, miR685), performance was not better than BUN, which was also elevated with grade 2 necrosis. Despite promising receiver operator characteristic (AUROC) values, novel urinary miRNA and protein biomarker abundance in cisplatin-treated DO mice with grade 1 tubule necrosis was not different from controls or from cisplatin-treated DO mice with grade 0 necrosis. These studies demonstrate a novel approach for using a genetically diverse rodent population to assess sensitivity of candidate biomarkers, especially for proposed clinical applications and also highlight limitations in using AUROC values for biomarker qualification.
Abhishek Venkatratnam (University of North Carolina)
Title: Collaborative Cross (CC) Mouse Population-Based Dose-Response Analysis of Liver Transcriptomic Responses to Trichloroethylene (TCE) at the Level of Genes and Pathways
Studies of gene expression are common in toxicology and provide important clues to mechanistic understanding of adverse effects of chemicals. At the same time, gene expression is heavily influenced by the genetic background of an individual, and the genotype-expression relationships may mediate inter-individual variability in toxic effects of chemicals. To date, few studies have dissected the dose- and genetic background-dependent effects of chemicals on the transcriptome. In this study, we tested the hypothesis that the genetically-diverse CC mouse population will enable characterization of genetic background-dose-expression relationships in response to the model liver toxicant TCE. Mice from 50 CC strains were exposed to single oral dose of TCE and tissues were collected. Livers were evaluated for both the level of trichloroacetic acid (TCA), a major TCE metabolite, and gene expression using RNA sequencing. Peroxisome- and fatty acid metabolism-related pathways were among the most dose-dependent enriched gene sets across the population. However, regression modeling revealed that nearly half of the TCE-induced liver transcriptomic effects were strain-dependent, with abundant evidence of strain/dose interaction, including in the peroxisomal signaling-associated pathways. Most of these effects on the transcriptome were similar whether TCE dose, or liver levels of TCA, were used in the regression. Interestingly, median pathway transcriptomics-based points of departure were similar to the apical points of departure for non-cancer and cancer effects used by the US EPA in deriving toxicity values from chronic rodent studies. Mapping of expression-genotype-dose relationships revealed significant associations; however, TCE effects in liver appear to be highly polygenic traits that are challenging to map with precision. This study demonstrates that the value of the population-based model lies in dose-response and mechanistic evaluations, but cautions that genetic mapping may be difficult because of the complexity in gene-exposure-dose relationships.
Prarthana Shankar (Oregon State University)
Title: The Role of a Novel Long Non-Coding RNA in the Regulation of Sox9b and Its Contribution to TCDD-Induced Toxicity Endpoints
In zebrafish, sox9b has been determined to be one of the most-reduced transcripts upon activation of the aryl hydrocarbon receptor (AHR) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We identified a novel long noncoding RNA named sox9b long intergenic non-coding RNA (slincR) located adjacent to sox9b, and previously demonstrated that slincR expression increases in an AHR2-dependent manner in response to multiple strong AHR ligands. SlincR is required for proper expression of sox9b and its known downstream targets, and reduced slincR expression significantly affects some aspect(s) of neuromuscular and/or sensory system development. In the current study, we performed capture hybridization analysis of RNA targets (CHART) RT-qPCR to determine if slincR binds to the sox9b promoter, and found that slincR is enriched at the 5’ untranslated region (UTR) of the sox9b locus in 48hpf DMSO and TCDD-exposed zebrafish. To understand slincR’s role in the TCDD-induced toxicity pathway, we performed RNA sequencing and clustered gene ontology enrichment analysis on 48hpf control and slincR morphants exposed to 0.1% DMSO or 1ng/mL TCDD. We identified significant enrichment in processes related to skeletal and cartilage development unique to TCDD-exposed control morphants, and angiogenesis and vasculature development unique to TCDD-exposed slincR morphants. To further investigate slincR‘s role in TCDD-induced toxicity phenotypes, we evaluated the cartilage of TCDD-exposed 72hpf zebrafish, and found a significant difference in the structure of the craniofacial cartilage in slincR morphants compared to control morphants. Additionally, a blood hemorrhage screen showed that TCDD-exposed slincR morphants at 48hpf had a lower proportion of hemorrhaging compared to TCDD-exposed control morphants. We also mined unpublished RNA-sequencing data from 16 PAHs, and found 6 PAHs caused a significant increase in both cyp1a and slincR expression, of which 3 are from the EPA’s priority PAH list. Collectively, our results suggest that slincR regulates sox9b expression by binding to the 5’UTR of the sox9b locus, regulates cartilage development, contributes significantly to TCDD-induced blood hemorrhaging, and is upregulated by multiple environmentally relevant PAHs. This study was supported by the SRP Grant P42 ES016465, NIEHS Core Center Grant P30 ES000210, and NIEHS Training Grant T32 ES007060.
MSBSS Webinar: Accepted! Tips On How to Get Into a Top Graduate Program
Wednesday, October 17, 2018 11:30 am
Webinar: Postdoctoral Fellow and Paper of the Year Award Recipients
Thursday, February 1, 2018 from Noon to 1:00 pm Eastern Time
Dr. Lacher will discuss how the interactions between the master regulatory of the transcriptional response to oxidative stress, NRF2, and the genome regulate gene expression to mediate redox homeostasis, metabolism, and proteostasis. She will also discuss the influence of single nucleotide polymorphisms (SNPs) o n NRF2-ARE binding and thus disease risk and how the experimental methods that she has developed can be applied to understand the broader relationship b etween SNPs and transcription factor binding. Dr. Bam will present his paper titled, “Dysregulated Immune System Networks in War Veterans with PTSD is an Outcome of Altered miRNA Expression and DNA Methylation,” which was published in Scientific Reports. He will discuss the identification of differences in DNA methylation and miRNA profiles associated with immune system biology in peripheral leukocytes in post-traumatic stress disorder (PTSD) patients and the rol e of epigenetic mechanisms in PTSD. These two presentations will highlight the exceptional research being conducted by young investigators in the molecular and systems biology specialty section.
Webinar: Accepted! - Preparing a Successful Graduate School Admissions Package
This webinar is a timely offering for students who are preparing graduate school applications and for mentors who are assisting students with this important career step.
Friday, November 10, 2017 12:00 pm
Eastern Standard Time (New York, GMT-05:00)
Sponsored by: Molecular and Systems Biology Specialty Section, Education Committee, Undergraduate Education Subcommittee, and Career Resources and Development Committee
The biomedical sciences offer a broad range of exciting and engaging prospects to pursue graduate training in cutting-edge research science. However, taking part in these opportunities requires a well-refined and impactful graduate school admissions application package. This interactive webinar will include short presentations on key aspects of the graduate school application from graduate program directors and admission committee members at leading graduate institutions. Then presenters will answer attendee questions in a live discussion.
Dr. Aaron Bowman, Associate Professor in Pediatrics, Neurology, and Biochemistry, and Director of the Training Program in Environmental Toxicology, at Vanderbilt Universitywill provide an overview of the graduate admissions process and perspectives on how admissions committees review applications, invite applicants for interviews, and make decisions on admissions offers. He will also discuss the role of GRE scores and grades.
Predicting Admission to the Ivory Towers: Grades, Scores, and Other Flowers: Overview of the Admissions Process—Aaron Bowman, Vanderbilt University [slides]
Dr. Dana Dolinoy, Associate Chair of Nutritional Sciences and Associate Professor of Environmental Health Sciences & Nutritional Sciences at the University of Michigan School of Public Health, will discuss how to select the best degree program for you and how to craft an impactful research statement.
Selecting the Best Degree Program For You and Crafting an Impactful Research Statement—Dana Dolinoy, University of Michigan [slides]
Dr. Lauren Aleksunes, Associate Professor and Director of the Joint Graduate Program in Toxicology at Rutgers University, will provide insight on how to write a meaningful personal statement that can help your application stand out.
Personal Statements: Where to Start and What to Include—Lauren Aleksunes, Rutgers University [slides]
MSBSS Webinar: 2017 Graduate Student Award Webinar
The first Annual MSBSS Graduate Student Award recipient webinar
Friday, November 17th at 12:00 Eastern time.
This webinar will highlight cutting-edge molecular and systems biology research that is currently being conducted by the recipients of the 2017 Molecular and Systems Biology Specialty Section's Graduate Student Research Award. The presentations will cover the molecular mechanisms of chemoresistance in non-small cell lung carcinoma, the role of non-coding RNAs in aryl hydrocarbon receptor-mediated exposure effects, and the use of CRISPR-Cas9 gene editing to identify genes associated with susceptibility to toxic exposures. These fields of research have broad implications across toxicology and would be of broad interest in SOT. Further, given the timely nature of the research that will be presented relative to the state of molecular biology as a whole, these presentations will also be of interest to audiences outside of the Society and will be a good opportunity to highlight the high-quality impactful research being conducted in the field of toxicology.
Recording Not Available