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Michigan State University Superfund Research Program
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MSU Superfund Research Program Newsletter

The MSU Superfund Research Program is pleased to send you the sixth edition of our electronic newsletter. Please take a moment to read over our recent activities.  

For more information on the MSU Superfund Research Program, please visit: http://iit.msu.edu/superfund2013/index.html.

In This Newsletter:

MSU Superfund Meets with External Advisory Committee

The MSU Superfund Program held a meeting on May 17-18, 2017 on the campus of MSU to meet with its External Advisory Committee. Each project and core presented recent progress over the two day meeting. The meeting culminated with a closed session of the External Advisory Committee to review the presentations and their review of the program will lead to recommendations for the future direction of the program. 

Research Spotlight

John LaPres, Ph.D., Michigan State University
Dr. Timothy Zacharewski, Ph.D., MSU
Dr. John LaPres, professor in the Department of Biochemistry and Molecular Biology at MSU, is the PI of Project 2 of the MSU Superfund: An Integrated Experimental and Computational Approach to Understand the Effects of Population Variability on the Shape of the Dose-Response Curve.
 
Traditional toxicology relies on single cell lines or inbred mouse models to assess the toxicity of any given compound.  Environmental exposures, however, occur across many different cell types and in genetically diverse populations.  This heterogeneity can drive differing responses dependent on many confounding factors, such as age, sex, concurrent exposures, genetic background, the cell-type and tissue exposed, and any potential underlying medical conditions.  Thus, extrapolating basic toxicology data derived from classical biological models to assess potential risk associated with environmental exposures in a diverse human population is difficult. For non-cancer causing chemicals, this risk assessment has been performed using a non-linear (i.e. threshold) model. The National Research Council (NRC) recently proposed that the dose response relationships (DRRs) for non-cancer causing chemicals would be more accurately assessed using a linear model if the genetic diversity of a population was taken into consideration. Given the potential implications of the NRC’s hypothesis for risk-management, as well as, the current limited supporting data, the goal of Project 2 of the MSU Superfund is focused on addressing the shape of the low-dose region of a population-level non-cancer DRR.

Dr. LaPres and his research group is using a mixture of in vivo and in vitro based models to assess the impact of population-level genetic diversity on the DRRs associated with the environmental toxicant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD is a persistent environmental contaminant that mediates its toxicity by activating the aryl hydrocarbon receptor (AHR).  The AHR is a ligand activated transcription factor that is linked to the toxicity of many toxicants found in Superfund sites. Specific endpoints associated with TCDD exposures of interest to the LaPres lab include immune suppression, gene expression changes, hormone synthesis in earl-pregnancy, and altered pregnancy success. By focusing on AHR-mediated toxicity, the LaPres laboratory hopes to generate the data necessary to aid risk-management in accurately determining safe exposure limits of TCDD and other planar aromatic hydrocarbons.  Additionally, the LaPres lab hopes to expand our understanding of the relationship between TCDD exposure, AHR activation, and cell signaling dysfunction.

In previous studies using human primary cells isolated from 52 unique donors, Dr. LaPres and his graduate student, Peter Dornbos, were able to show that the DRR for TCDD-induced B cell inhibition was most accurately modelled using non-linear equations, suggesting that a large amount of genetic diversity does not drive the DRR towards linearity.  To address the limitations in the human B cell model, the laboratory is now taking advantage of the powerful genetics inherent in the collaborative cross (CC) panel of mice strains.  By assessing the response of numerous CC mouse strains, the LaPres laboratory will be able to model the genetic diversity in the human population.  More importantly, by leveraging the genetic tools available for CC strains, they will be able to identify genetic modifiers of AHR signaling that potentially drive individual susceptibility to TCDD-mediated toxicity.  The ultimate goal of the project is to provide risk assessors the necessary data to inform their decisions on safe exposure limits, identify genetic variants that may influence susceptibility to TCDD exposures, and to identify novel genes, proteins, and signaling pathways that influence AHR biology.

MSU Superfund Graduate Student Wins Prestigious Fitch H. Beach Award


Maggie R. Williams, MSU graduate student working with Dr. Syed Hashsham  (Project 4) was the first place recipient of the Fitch H. Beach Award, the most prestigious award in the College of Engineering at Michigan State University. She presented her work 'Role of MicroRNAs in Host-Gut Microbiota Communication Following Dioxin Exposure.' The Fitch H. Beach Awards are based on a review of students' academic and professional records and on an oral presentation of their research. Nominees receive a stipend, certificate, and a medal to be worn at graduation.

MSU SRP Presents at May 2017 CAG Meeting 


Dr. Norbert Kaminski, Project 1, and Dr. Brian Teppen, Project 6, gave presentations at the May 2017 Saginaw-Tittabawassee Rivers Contamination Community Advisory Group Meeting in Freeland, MI. Dr. Kaminski presented, "Overview of MSU's National Institute of Environmental Health Sciences (NIEHS) SRP Project and the MSU Center" and Dr. Teppen presented, "Collaborative research efforts on activated carbon and its potential use for remediation of dioxin-like compounds."

The Saginaw-Tittabawassee Rivers Contamination Community Advisory Group (CAG) is composed of a broad cross-section of representatives from Bay, Midland and Saginaw counties. It serves as a focal point by which the residents of this community can exchange information concerning contamination issues affecting their community with EPA, state regulatory agencies of Michigan, potential parties responsible for contamination and other federal agencies involved in site cleanup. The CAG meets bimonthly and the MSU-SRP actively attends these meeting and has served as a resource to address questions on issues of environmental contamination.  At the May meeting, there were many new CAG members present and Dr. Kaminski gave an overview of our SRP program, followed by a presentation by Dr. Teppen on the potential role that activated carbon could play in remediation efforts.  The new members were enthusiastic to learn about our Superfund program and asked many insightful questions. The representative from Dow Chemical Company also discussed their efforts in the exploration of activated carbon for remediation, which was also well received.

Kaminski Receives George H. Scott Memorial Award from The Toxicology Forum
 

Dr. Norbert Kaminski (Project 1) was awarded the George H. Scott Memorial Award at the 43rd Annual Summer Meeting of The Toxicology Forum, held July 10-12, 2017 in Annapolis, Maryland. Dr. Kaminski gave the George Scott Award Lecture at the meeting on, "Role of the Aryl Hydrocarbon Receptor in Human Stem Cell to B Cell Lineage Commitment."

George H. Scott, a Procter & Gamble scientist who gained worldwide respect for his tireless efforts and contributions in the fields of human and environmental toxicology is remembered through an annual award established by The Toxicology Forum in 1983. His unfailing support of the Forum in its early days played a major role in its success. The award is given to those who have demonstrated an outstanding role in developing and applying the science of toxicology, and honors the memory of George Scott.
 
The Toxciology Forum had this to say about Dr. Kaminski:

Dr. Norbert Kaminski is an established, highly respected academic leader in toxicology. His research, primarily involving immunotoxicology, is highly cited. He has trained and mentored many pre and post-doctoral students in toxicology and pharmacology. He also has provided exemplary service and leadership to the discipline of toxicology. These contributions support his well-deserved reputation as a scientist, educator, mentor, and leader.

Article Spotlight
 

MSU Superfund researchers have published a research article titled, "Isothermal assay targeting class 1 integrase gene for environmental surveillance of antibiotic resistance markers," in the Journal of Environmental Management. 

This publication was a product of our “Citizen’s Science” project, which was a survey of natural microbial populations within the Tittabawassee and Saginaw river watershed for microbial degradation activity of dioxin and dioxin-like compounds, and also for microbial populations developing antibiotic resistance, another growing environmental health issue. This water shed that runs through four local Michigan communities (Midland, Freeland, Saginaw and Bay City) is contaminated with pollutants, particularly dioxins. The project involved building capacity from volunteers from this community to conduct research, as well as transfer of technology developed by our SRP investigators; specifically providing the community with access to a hand-held DNA analysis device, termed Gene-Z. Routine complexities in molecular diagnostics, such as sample processing, were circumvented using the Gene-Z that can be used by relatively untrained personnel.  Four community members are co-authors on this paper as well as a visiting summer student.

View the abstract

Recent Publications


Boyd SA, Sallach JB, Zhang Y, Crawford R, Li H, Johnston CT, Teppen BJ, and Kaminski, NE. (2017) Sequestration of TCDD by activated carbon eliminates bioavailability and the suppression of immune function in mice. Environ Toxicol Chemistry. (In press)

Phadnis-Moghe AS, Kaminski NE. (2017) Immunotoxicity Testing using Human Primary Leukocytes: An Adjunct Approach for the Evaluation of Human Risk. Curr Opin Toxicol. (In press)

Fader KA, Nault R, Zhang C, Kumagai K, Harkema JR, Zacharewski TR. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-elicited effects on bile acid homeostasis: Alterations in biosynthesis, enterohepatic circulation, and microbial metabolism. Sci Rep. 2017 Jul 19;7(1):5921. PubMed PMID: 28725001.

Samhan FA, Stedtfeld TM, Waseem H, Williams MR, Stedtfeld RD, Hashsham SA. On-filter direct amplification of Legionella pneumophila for rapid assessment of its abundance and viability. Water Res. 2017 Sep 15;121:162-170. PubMed PMID: 28527390.

Stedtfeld RD, Stedtfeld TM, Waseem H, Fitschen-Brown M, Guo X, Chai B, Williams MR, Shook T, Logan A, Graham A, Chae JC, Sul WJ, VanHouten J, Cole JR, Zylstra GJ, Tiedje JM, Upham BL, Hashsham SA. Isothermal assay targeting class 1 integrase gene for environmental surveillance of antibiotic resistance markers. J Environ Manage. 2017 Aug 1;198(Pt 1):213-220. PubMed PMID: 28460328.

Waseem H, Williams MR, Stedtfeld T, Chai B, Stedtfeld RD, Cole JR, Tiedje JM, Hashsham SA. Virulence factor activity relationships (VFARs): a bioinformatics perspective. Environ Sci Process Impacts. 2017 Mar 22;19(3):247-260. PubMed PMID: 28261716.

Fader KA, Nault R, Kirby MP, Markous G, Matthews J, Zacharewski TR. Convergence of hepcidin deficiency, systemic iron overloading, heme accumulation, and REV-ERBα/β activation in aryl hydrocarbon receptor-elicited hepatotoxicity. Toxicol Appl Pharmacol. 2017 Apr 15;321:1-17. PubMed PMID: 28213091.

Kovalova N, Nault R, Crawford R, Zacharewski TR, Kaminski NE. Comparative analysis of TCDD-induced AhR-mediated gene expression in human, mouse and rat primary B cells. Toxicol Appl Pharmacol. 2017 Feb 1;316:95-106. PubMed PMID: 27913140.

Ahmad F, Stedtfeld RD, Waseem H, Williams MR, Cupples AM, Tiedje JM, Hashsham SA. Most probable number - loop mediated isothermal amplification (MPN-LAMP) for quantifying waterborne pathogens in <25min. J Microbiol Methods. 2017 Jan;132:27-33. PubMed PMID: 27856278.
Copyright © *|2017|* *|Michigan State University Superfund Research Program|*, All rights reserved.

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