Cross-ORD Post-Doctoral. Fellowship Program Haluk Ozkaynak and Bruce Jones USEPA Office of Research and Development, National Exposure Research Laboratory, RTP, NC & The EPA's Office of Research and Development (ORD) is comprised of several different laboratories and centers whic share the common goal of providing research that can be applied to better protect the environment and human health Partnerships and collaboration between labs and centers serve as an effective mechanism for the exchange of ideas and the understanding of research perspectives between related scientific disciplines. In the summer of 2005, EPA- ORD initiated a new cross-ORD post-doctoral fellowship program, which is designed to promote greater collaboration between ORD's labs and centers. After a nation-wide search, the cross-ORD post-doctoral fellows were selected in both the human health and ecosystems research areas and assigned primary, secondary, and tertiary mentors based upon the interdisciplinary nature of their specific research focus. Each cross-ORD post-doctoral fellow developed a detailed research plan jointly with his or her mentors. These research plans outlined collaborative research projects to be conducted during the four year fellowship, along with the anticipated impact that each project would have on supporting the mission of the EPA. Research topics of the nine cross-ORD fellows include: 1) Computational systems biology modeling to predict toxicological mechanisms (Michael Breen), 2) Characterization of environmental exposures and associated health risks in aging populations (Doug Johns), 3) Applications of exposure analysis tools in environmental epidemiology (Mary Johnson), 4) Building realistic biologically based pharmacokinetic models for predicting susceptibility in aging populations (Janice Lee), 5), Molecular modeling of the interaction between environmental chemicals and targets for chemical toxicity (Melissa Pasquinelli), 6) Predictive ecological niche modeling in aquatic systems (Kristina McNyset), 7) Quantifying key drivers of change in the built environment and their interaction with changes in the natural environment (Johns Thomas), 8) Biotic responses to hydrologic alteration in suburban headwater streams and potential for storm water mitigation (Allison Roy), and 9) Effectiveness of best management practices in mitigating storm water runoff and water quality (Yu Zhang). In addition to providing excellent interdisciplinary scientific training for the post-doctoral fellows, it is anticipated that the findings of each of these projects will result in the publication of several peer-reviewed journal articles. EPA envisions that this program will foster further collaboration between the different ORD labs and centers, thereby leading to more focused research strategies and a better understanding of the relationships between environmental pollution, exposure, and human and ecological health. 4* Disclaimer: although this work was reviewed by EPA and approved for publication, it may not necessarily reflect official Agency policy. NCEA epascienceforum VtHif • tW Cfflrinxwmir • TWr Fuiuf* ------- Doug Johns1 Janice S. Lee1 Mentors: Bob Sonawane1, Jackie Moya1, Tom McCurdy2, Vernon Benignus3 'NCEA, Washington, DC; 2NERL 3NHEERL, Research Triangle Park, NC Agpng [initiative Environmental Exposures and Health Implications in Older Adults Mentors: Chris Corton1, Mike Devito1, Mike Tornero2 1NHEERL, 2NERL, Research Triangle Park, NC Building realistic biologically-based pharmacokinetic models for predicting susceptibility in aged populations Research Goal: Provide a more complete understanding of environmental exposures and the associated health risks in aging populations Research Goal: Improve pharmacokinetic models of the aged by incorporating genomic information on the differences in xenobiotic metabolism gene expression between young and old populations Projects • Organize a workshop to discuss the aging as a susceptible population in conducting risk assessments • Develop an Exposure Factors Handbook for the aging • Conduct a large scale review and analysis of age-related changes in phase I, phase II, and antioxidant enzyme activities • Develop a PBPK model to predict the kinetic behavior of specific neurotoxicants in older adults Anticipated Outcome This research will provide information that can be used by risk assessors to characterize age-related changes in exposures to environmental chemicals, and understand how the aging body responds to toxic stressors Hazard Identification * Exposure Assessment Risk Characterization Risk Assessment Paradigm Example of a physiologically based toxicokinetic model for an inhaled VOC. Projects • Generate gene expression profiles for xenobiotic metabolizing enzymes (XMEs) in the aging rat, mouse & human • Generate gene expression profiles in the aging rat, mouse & human after exposure to toluene & other chemicals to determine changes in XMEs • Incorporate genomic information in the construction and improvement of a rodent & human PB-PK model for the aged Anticipated Outcomes • Identification of common and disparate changes in XMEs during aging between tissues and across species • Integration of XME gene expression behavior in PB-PK models of different life stages that help to predict toxicity in different subpopulations AlTHNMIWOKtAM Scanned image Affymetrix chip I0***] mm I -—•! IK | —EP ra rjrliwi lis] T m J- - ¦ fcs |1AW I ~CSr- Cluster analysis Pathway analysis (KEGG) ------- John Thomas1 / Mentors: Mike Slimak, Anne Grambsch1, Jim Wickham2' / Hale Thurston3: 1NCEA, Washington, DC; 2NERL, Research Triangle Park, NC; 3NRMRL, Cincinnati, OH Quantifying key drivers of change in the built environment and their interaction with changes in the natural environment Research Goals • Improve the treatment of socioeconomic factors in ecological analyses. • Quantify the value of environmental amenities in property markets. Projects • Socioeconomic Evaluation of Watershed Recovery • Valuation of Climate Sensitive Natural Amenities • Integrated Climate Land Use Scenarios Socioeconomic Evaluation of Watershed Recovery Basic Approach Cities and Villages • H^| mf - p 4 -PG Townships Watersheds • Aggregation of key demographic, public finance and construction activity data to a watershed level. • Cluster analysis to define the socioeconomic profiles of watersheds. Anticipated Outcomes • A decision support tool for evaluating stakeholder characteristics by watershed. Based on a methodology that can be replicated in any US state or region. Allison Roy1 Mentors: Bill Shuster1, Ken Fritz2, Tony Olsen3, David Walters2 1NRMRL, 2NERL. Cincinnati, OH; 3NHEERL, Corvallis, OR Biotic responses to hydrologic alteration in suburban headwater streams and potential for storm water mitigation Research Goal 1: Characterize the hydrological and ecological effects of urbanization on headwater streams Relating stormflow and base- flow hydrology, watershed urbanization, & stream biota. Anticipated Outcomes Stormwater best management practices (BMPs) distributed in residential watershed using a voluntary, economic auction. • Refine NERL protocol for sampling headwater streams • Identify indicators of disturb- ance for protecting water resources & ecosystem health • Provide baseline for restoring headwater streams Research Goal 2: Evaluate the potential for stream ecosystem restoration via stormwater management Photo: Clear Water Con- servancy http://www.urb anwaterqualitv. orq/rairiGardens /rqindexl .htm Anticipated Outcomes • Establish feasibility of stream restoration using an auction • Determine benefits of BMPs and potential for ecosystem recovery Photo: Urban Resources & Borderland Alliance Network http://www.urbanwaterquality.org/RainGardens/rqindex1.htm ------- Michael Breen1 Mentors: Rory Conolly1, Haluk Ozkaynak2 1NCCT, 2NERL, Research Triangle Park, NC Computational Systems Biology Modeling to Predict Toxicological Mechanisms jTDXtCClLDBY Melissa Pasquinelli1 Mentors: Jim Rabinowitz1, Susan Laws2, Mike Tornero3 1NCCT, 2NHERL, 3NERL, Research Triangle Park, NC Molecular Modeling as a Tool for Assessing Chemical Toxicity Research Goal; Develop and apply mechanistic mathematical models to predict the biological effects of environmental chemical exposures Projects • Develop a mechanistic mathematical model of intratesticular and intraovarian metabolic network that mediates steroid synthesis to describe dose-response for endocrine disruptors • Develop visualization and analysis tools to compare computational systems biology model predictions of protein concentrations with western blot data Anticipated Outcomes • Improve our understanding of the dynamic dose-response behavior at the molecular level for risk assessments with endocrine disruptors • identity and link new molecular biomarkers that are indicative of the ultimate adverse effects from endocrine disruptors Mathematical Modeling of Steroidogenesis in Fish Gonads Rate-limiting reaction Conceptual model of the intratesticular steroidogenic pathway in fish for the conversion of cholesterol (CHOL) to the secreted steroid hormones ketotestosterone (KT), testosterone (T), and estradiol (E2). The first reaction rate (v1) with the P450scc enzyme is the rate limiting step. Research Goal; Develop and apply molecular modeling tools in order to facilitate the assessment of mechanisms for chemical toxicity Projects • Use the macromoiecular target-toxicant paradigm to develop a computational His23i approach for the evaluation of potential toxicological effects of environmental chemicals, and then utilize this approach study potential endocrine disrupting chemicals (EDCs) Qln60 v daidzein • Use molecular modeling to decipher the mechanism of metabolism and other toxicologically relevant processes Anticipated Outcomes • Improve the predictive ability of screen tools for chemical toxicity by integrating molecular modeling with complementary '(Ihi60 17p-estradiol experimental and computational approaches, which will then be used to categorize and prioritize chemicals for further testing • Improve systems biology models by integrating quantities that are calculated with molecular modeling methods, such t the rates of metabolism of pyrethroid chemicals The pictures to the above right show calculated poses of the Estrogen Receptor with its natural ligand, 17b-estradiol, and two weak environmental estrogenic compounds, daidzein and morin. The hydrogen bonds formed between the chemical and the protein receptor (indicated by gray dotted lines) differ for each chemical and hence impact its binding properties. ------- Kristina McNyset1 / Mentors: Bruce Jones2, Tony Olsen1, Henry Walker3, James Wickham4, Brian Hill5, Henry Lee1, Lester Yuan10 1NHEERL, Corvailis, OR; 2NERL, Las Vegas, NV; 3NHEERL, Narragansett, Rl; 4NERL, Research Triangle Park, NC; 5NHEERL, Duluth, MN; 6NHEERL, Newport, OR; 7NCEA, Washington, DC Predictive ecological niche modeling in aquatic systems Research Goal: Develop spatially explicit models of biotic conditions in aquatic systems Projects • Determine best methods for predictive modeling of species distributions in stream systems • Integrate point-sampled and landscape-level data in predictive ecological niche modeling analyses in freshwater systems • Develop ecological data sets for use in spatially explicit modeling in estuarine systems Anticipated Outcomes A set of modeling tools, datasets, and models that will increase our understanding of biotic conditions in aquatic systems Predicted Distribution of the nuisance diatom species Didvmosphenia geminata (Lvngbve) M. Schmidt This is the 10 best-model subset from a GARP (Genetic Algorithm for Rule-set Prediction) model run of 200 models. The color gradient from pinkto dark red indicates increasing model agreement between best-subset models. The green circles are the training data used the build the models taken from the USGS NAWQA project, the yellow squares are the testing data taken from the EPA WEMAP project. Overall omission was 110% at a threshold of 5 models. ------- Epidemiology Mary Johnson1 Mentors: Lucas Neas1, Haluk Ozkaynak2 1NHEERL 2NERL, Research Triangle Park, NC Applications of exposure analysis tools in environmental epidemiology a monitoring locations for DCHS Anticipated Outcomes • Improve connections between traditional exposure assessment and epidemiological paradigms Environmental Health Perspectives, March 2006 cover photo: www.ehponline.org El Paso Children's Health Study participant performing spirometry Generate new ideas and methodologies to improve scientific understanding of health effects related to near-roadway exposures to traffic-related air pollutants. Research Goals Develop and refine exposure analysis tools for assessing traffic-related air pollutants and apply these tools in epidemiologic studies of human health. Projects • Evaluate existing metrics for estimating personal exposures to traffic-related pollution using health and exposure assessment data from the El Paso Children's Health Study, the Detroit Children's Health Study (DCHS), and Mechanistic Indicators of Childhood Asthma (MICA) study, and exposure data from the Detroit Exposure Aerosol Research Study (DEARS). Traffic near 12 Mile Road in Detroit: www.core.org.cn • Develop advanced exposure assessment techniques based on indoor/outdoor/personal measurements, housing characteristics, time-activity data, and dietary patterns (DEARS, MICA), as well as GIS-based variables and household characteristics (DCHS), • Apply and compare advanced exposure metrics using health outcome data from DCHS and biological data from MICA. Air monitoring at Detroit area schools for DCHS ------- Yu Zhang Mentors: William Shuster1, Hale Thurston1, Matthew Heberling2, Kenneth Fritz2 1NRMRL, Cincinnati, OH; 2NERL, Cincinnati, OH Effectiveness of best management practices in mitigating storm Research Goals • Determine the processes controlling the differences in runoff response characteristics of catchments. • Separate transient stream flow features due to rainfall variability from the inherent difference in catchment physiology. • Develop process-based modeling framework for projecting the hydrologic impacts of best management practices (BMPs) and the associated uncertainties Projects n I Climate variability Runoff Model w i v • Examine climate variability of rainfall BMP and establish the response characteristics of neighboring catchments independent of rainfall • Incorporate BMPs in modeling frameworks and determine the accuracy in the model predictions by comparing the model results with observed stream flow data • Characterize uncertainties in the projected impacts of BMPs by incorporating climate variability Anticipated Outcomes • Physically based modeling framework for projecting the impacts of BMPs with readily available GIS data as input Guidelines for decision making concerning the BMPs given uncertainties stemming from the variability and trends of climate Impacts of BMPs? ------- |