Environmental Biomarkers Core

Goal

The overall goal of the Environmental Biomarkers Core (EBC) is to provide bioanalytical services in support of ChicAgo Center for Health and EnvironmenT (CACHET) members conducting environmental health research at the University of Chicago (UofC) and University of Illinois at Chicago (UIC). By providing the necessary experimental expertise to assess a wide range of environmental biomarkers, the EBC directly contributes to CACHET’s mission to mitigate environmental health inequities within our communities. Toward that end, the EBC consists of two complimentary Sub-Cores: 1) a mass spectrometry-based Environmental Exposures Sub-Core that is P30-specific in services and resources available to members, and 2) a Biomarkers of Exposure Effects and Susceptibility Sub-Core that leverages existing institutional resources at UofC and UIC and streamlines services to members. The P30-specific Environmental Exposures Sub-Core at UIC will use mass spectrometry to assess toxic chemicals, heavy metals and metalloids, herbicides, pesticides, perfluoroalkyl substances, steroids and DNA oxidation products, among others, in both biological and environmental samples. New assays for environmental compounds will be developed and validated as needed by CACHET investigators. The Biomarkers of Exposure Effects and Susceptibility Sub-Core will leverage established institutional strengths in microbiome sequencing, metabolomics, proteomics, genomics, epigenomics and transcriptomics on the two campuses. Further, bioinformatics support for all CACHET PI-initiated research projects and Facility Core activities will be provided from established institutional cores at both partner institutions. For all of these services, CACHET members will enjoy priority access and subsidized rates for environmental health research projects provided by Center resources and leveraging institutional cost-sharing of intellectual expertise, management platforms and heavy investments in high-end instrumentation. These combined resources help address the EBC mission to provide qualitative and quantitative data regarding biomarkers of exposure, disease and therapeutic responses as well as levels of environmental contaminants in human subjects, model systems and environmental samples at subsidized rates and with priority access to Center members.

Specific Aims

Aim 1. Determine levels of heavy metals and metalloids (e.g., As, Pb, Hg, Se) in biological and environmental samples collected by CACHET members; support sample processing, storage, ICP-MS analysis and data reporting for EHS research.

Aim 2. Develop LC-MS/MS-based mass spectrometry assays for quantitative determination of small molecules and metabolites of environmental toxins, pesticides, PFAS, etc.

Aim 3. Assess microbiota and microbial population dynamics in environmental (water and air) samples collected by CACHET members; support sample processing, storage, DNA sequencing and data analysis for research conducted by NIEHS-funded CACHET investigators.

Aim 4. Provide microbial profiling (16S and metagenomics) and microbial metabolite assessment and associated bioinformatics services to CACHET members investigating environmental effects on the human microbiome (in stool and saliva) and its metabolites (in stool and blood) as well as influence of the host microbiome on environmental health effects.

Aim 5. Provide host genomic, epigenomic, transcriptomic and associated bioinformatics services to CACHET members for studies evaluating genetic susceptibility to environmental contaminants, toxicogenomics and gene–environment interactions.

Research Strategy

Overview

The Environmental Biomarkers Core (EBC) of the ChicAgo Center for Health and EnvironmenT (CACHET) is a newly reorganized Facility Core assembled to enable transition to a fully-funded environmental health sciences (EHS) Core Center. During the initial funding cycle, the Biomarkers Core had two components to address the needs of CACHET members: a Mass Spectrometry Core at the University of Illinois at Chicago (UIC) for measurement of analytes in environmental and biological samples, and a Microbiome Core at the University of Chicago (UofC) for bodily and environmental microbial monitoring. Due to a reduced budget (60% level), most of our resources during the first 3 years were directed to: 1) establishing a state-of-the-art ICP-MS platform in a dedicated suite at UIC, leveraging CACHET funds with an NSF instrument grant and institutional resources; 2) establish selected chemical-based liquid chromatography with tandem mass spectrometry (LC-MS/MS) assays for Center members’ needs, and 3) provide unique access to expansive microbiome facilities at Argonne National Labs (UofC) under the direction of Jack Gilbert, PhD. In preparation for expanded services in the next funding cycle, CACHET surveyed and interviewed its members to identify essential bioanalytical services that would further support their EHS research. While the Mass Spectrometry (MS) and Microbiome Sub-Cores provides valuable services to several CACHET members, many unmet needs were identified that include expanded metabolomics for targeted and untargeted molecules, DNA/RNA-omics for exposure research that includes larger epidemiology studies, novel technologies and robust bioinformatics services. To meet these needs, CACHET reorganized the former Biomarkers Core into the EBC, with two sub-cores: 1) an MS-based Environmental Exposures (EE) Sub-Core that is P30-specific in services and resources available to Center members, and 2) a Biomarkers of Exposure Effects and Susceptibility (BEES) Sub-Core that leverages existing institutional resources at UofC and UIC and streamlines services to members. Together, the new EBC will:

  • Provide CACHET members access to analytical support that enables determination of exposures to environmental toxins in biologic and environmental samples as well as biomarkers that identify physiological consequences of and susceptibility to such exposures;
  • Develop new analytical methods and acquire new instrumentation to support evolving EHS research;
  • Offer expertise in design and interpretation of analytical measurements for Center members;
  • Provide methodologic training for CACHET Junior Investigators; and
  • Provide streamlined services, priority access and subsidized fee structures for Center members.

By combining unique resources located at each institution into a single core, CACHET members will gain seamless access to instrumentation and expertise within the EBC regardless of campus affiliation. In addition, CACHET members receive prioritized service and a subsidized fee structure for all EE Sub-Core assays and a co-pay model for environmental research projects for the BEES Sub-Core. Importantly, the selective combination of resources within EBC allows CACHET investigators to obtain analytical measurements locally and in a timely fashion rather than shipping samples and materials out-of-state for analysis, as was the practice prior to the establishment of CACHET. As a result, research productivity dependent on measurement of metals, pesticides, and many other environmental toxins as well as shifts in microbial populations and their metabolic signatures has been dramatically enhanced and is expected to increase with expansion of services to further augment NIEHS-funded research at UofC and UIC. The EBC will continue to develop new assays and analytical procedures to support research efforts within CACHET, which include development and validation of new methods for detection and quantitative analysis of specific compounds/emerging chemicals in environmental or human/animal samples or measurement of new and emerging biomarkers of exposure (e.g., targeted/untargeted metabolites) and effects (e.g., short-chain fatty acids, bile acids) in biomedical specimens.

Organization and Leadership

 

 

Richard D. Minshall, PhD, is Professor of Pharmacology and Anesthesiology in the College of Medicine at UIC, with a research focus on pulmonary disease and molecular mechanisms of lung injury. Dr. Minshall currently serves as Co-Leader of the CACHET Biomarkers Core, implementing services within the RRC Mass Spectrometry Core (RRC-MSC). At UIC, he previously served as Director of the RRC and as Associate Director of Shared Resources for the University of Illinois Cancer Center. He is the current Co-Director of Team Science for the UIC Center for Clinical and Translational Sciences. His efforts have been instrumental in reorganizing and rejuvenating core service facilities critical to basic, translational and clinical research activities at UIC. As the RRC Director, he was instrumental in upgrading the RRC-MSC as well as other core facilities for NMR, flow cytometry, imaging, genomics, gene editing, single cell proteomics, transcriptomic profiling, biobanking and bioinformatics, which are all important for CACHET investigators. In addition to serving the UIC research community, Dr. Minshall plays a central role in the Chicago Biomedical Consortium (CBC), a collaborative agreement between UIC, UofC and Northwestern University that provides access for all investigators to shared resources at each institution at internal rates. As a UIC leader and representative to the CBC open access executive advisory panel that directs acquisition of new shared instrumentation not otherwise available in Chicago, he has enabled development of quantitative assays for analysis of a wide variety of biomarkers such as isoprostanes, DNA oxidation products and sulfatides in clinical specimens, and environmental pollutants, e.g BPA, heavy metals. Dr. Minshall’s primary role as EBC Co-Leader is to provide direction, advice and “lead blocking” that enables CACHET members to access relevant key Facility Cores at UIC and UofC and to help coordinate access and P30-subsidized copay mechanisms that reduce costs to PIs for facility/service fees while providing high-quality prioritized access to critical instrumentation and expertise.

Eric G. Pamer, MD, is Director of the DFI and Microbiome Center and Professor of Medicine and Microbiology at UofC. He is a renowned physician–scientist who specializes in immune defense against infections associated with cancer treatment, with a research focus on the microbiome’s impact on infection resistance. Dr. Pamer was previously the Chief of Infectious Disease at Memorial Sloan Kettering in NYC, Director of the Lucille Castori Center for Microbes, Inflammation and Cancer and Professor at Weil Cornell Medical University. He is a member of the NIH-NIAID Board of Scientific Counselors and the Bill and Melinda Gates Foundation’s Global Health Scientific Advisory Committee. His multidisciplinary expertise encompasses microbial genomics, transcriptomics and metabolomics in relation to health and immunity. At DFI, Dr. Pamer’s research team promotes wellness through groundbreaking science on the immune system, genetics, the microbiome and their shared environments. UofC has provided significant research resources and infra-structure support (e.g. physical infrastructure, major instrumentation, multiple faculty recruitment slots), which benefit the newly streamlined EBC to support CACHET’s mission. Dr. Pamer’s role as Co-Leader of the EBC entails providing direction, oversight and operational guidance to core services pertaining to analyses of micro-biome, microbial metabolites and other -omics-related assays, enabling CACHET members at UofC and UIC to timely and seamless access while ensuring quality and prioritization to meet evolving CACHET needs.

Approach

The EBC will provide a suite of measurements to CACHET investigators by combining unique resources available at UIC (ICP-MS, LC-MS/MS, MALDI-TOF etc.) and UofC (microbiome, metabolomics, GC-MS) with DNA and RNA sequencing and bioinformatics at each site. Making these resources equally available to CACHET members on both campuses will continue to increase collaborations and output. Importantly, providing stream-lined, prioritized and subsidized access to existing resources will enhance the productivity of CACHET researchers. EBC will provide services in five areas: 1) LC-MS and GC-MS of biomarkers and environmental toxins; 2) ICP-MS metal analysis; 3) microbiome and metabolomics; 4) DNA/RNA -omics; and 5) bioinformatics.

Environmental Exposures (EE) Sub-Core

The EE Sub-Core is a P30-specific unit that partners with the UIC RRC-MSC to leverage its equipment and expertise, providing CACHET members with identification and quantitative measurements of analytes in biological and environmental samples. The RRC-MSC/EE Sub-Core, equipped with eight modern mass spectrometers available to CACHET members, recently re-located to renovated space in the Center for Structural Biology Building, adjacent to the UIC- School of Public Health (SPH). This unit of the EBC is located centrally within the Illinois Medical District and is easily accessible. The facility and labs have a secure card-reader entrance affording 24-hour availability and adjacent parking to all staff and users. Investigators who are frequent users from off-campus locations (e.g., UofC PIs) are given special identification cards for laboratory access. Experienced users may arrange to start experiments before the staff leaves and continue after hours. Data are archived in an informatics center maintained by the RRC and may be retrieved remotely for processing.

Leadership

 

Stephanie Cologna, PhD, will serve as Academic Leader for the EE Sub-Core. Dr. Cologna is an Associate Professor of Chemistry in the College of Liberal Arts and Sciences at UIC and Academic Director of the RRC-MSC. She is an expert in MS and is fully engaged in providing expert advisory support to Core Director Hui Chen in the design of new MS assays, trouble-shooting problematic assays, and interfacing with Dr. Minshall and other CACHET and campus members on MS, instrumentation, personnel needs and, importantly, rigor and reproducibility. Dr. Cologna received her PhD in analytical chemistry, specifically mass spectrometry from Texas A&M University, with postdoctoral training at the NIH working on proteomics of rare genetic disorders. Dr. Cologna will ensure that the P30-specific EE Sub-Core and affiliated institutional MS core facilities at UIC and UofC are an educational resource for CACHET investigators, postdoctoral fellows and staff. Dr. Cologna has a training record in MS techniques and established the annual Chicago Mass Spectrometry Day to provide MS education to regional scientists. For CACHET, Dr. Cologna works with Drs. Minshall and Prins to implement the specific aims for the EE Sub-Core, which include critical new instrumentation for analysis of heavy metals, metabolomics/small molecule identification and quantification that specifically addresses critical research needs highlighted in the 2019 CACHET membership survey.

 

Hui Chen, PhD, is Director of the RRC-MSC and the CACHET EE Sub-Core Co-Leader at UIC. He is a technical expert in MS for heavy metals, small molecules, lipids, metabolites and proteins. Dr. Chen currently oversees daily operations of this critical MS-based core resource. Dr. Chen received his PhD in analytical chemistry and has worked with MS for >20 years, including liquid and gas chromatography and various types of MS such as FT-ICR-MS, MALDI-TOF, Q-TOF, QQQ and ICP-MS. Dr. Chen will train CACHET faculty and senior postdoctoral fellows in LC-MS/MS and ICP-MS sample preparation and analysis. He will also coordinate proteomics analyses for BEES as needed by CACHET members.

 

Key Accomplishments

  • Purchased a Perkin Elmer NEXion-2000 ICP-MS, built a dedicated suite, and activated services for heavy metal analysis including high throughput sampling, microwave digestion and metal speciation capabilities;
  • Enrolled and participated (certified) in the Quebec Multi-element External Quality Assessment Scheme to ensure service quality in metal analysis across multiple matrices;
  • Established quantitative LC-MS/MS assays for pesticides, herbicides, bisphenols and PFAS;
  • Purchased a new Q-Exactive Orbitrap LC-MS/MS and developed tandem mass tag protocols for quantitative proteomics analysis for protein biomarker identification and quantification;
  • Established untargeted metabolomics and lipidomics assays for biomarker discovery;
  • Recruited Stephanie Cologna, PhD, as Academic Leader of CACHET EE Sub-Core;
  • Hired Assistant Manager for EE Sub-Core, Dr. Jayathilaka (0.5 FTE for CACHET), who will focus on metals analysis by ICP-MS and MS-based targeted assays mentioned above.
  • Implemented the iLab research management and billing system, which streamlines billing for subsidized and co-pay mechanisms and tracks Core usage by CACHET members regardless of institutional affiliation.
  • Established a service hub to facilitate CACHET member’s needs in multi-analyte analysis of completed in-house and outsourced services. Results are returned to users in a single report.

 

Biomarkers of Exposure Effects and Susceptibility (BEES) Sub-Core

The overall goal of BEES Sub-Core is to advance EHS research of CACHET members by providing ready access to state-of-the-art “-Omics” technologies and expertise across the two campuses, facilitating effective utilization of resources, enhancing training opportunities and providing subsidized rates for services to Center members. To accomplish this goal, the BEES Sub-Core leverages existing institutional resources at UofC and UIC in microbiome analysis, metabolomics, proteomics, genomics and bioinformatic services. To enable streamlined access to these varied services by CACHET members and provide advice on appropriate experimental design and resource utilization, each BEES Sub-Core has a Center-supported Facilitator who is the director of that institutional facility core and a subject-matter expert. In addition to providing guidance and priority access to CACHET members, they will provide training to CACHET investigators who wish to master these technologies, particularly young investigators and those new to the fields. The BEES Sub-Core uses the Office of Shared Research Facilities cores (OSRF) central web-based ordering system at UofC for services and subsidy/co-pay requests which enables efficient turnaround time for all CACHET members on both campuses. This system permits tracking of subsidized services and Core/Unit utilization in a centralized database for efficient metrics analysis of facility usage and outcomes.

Key Accomplishments

  • Trained Argonne Microbiome Core staff and developed specimen receipt protocols for EHS studies;
  • Streamlined and refined microbiome sequencing assays, sample collection, processing procedures and bioinformatics pipelines for profiling gut and saliva microbiome in population studies;
  • Established protocols and collection procedures for air sample microbiomes from South Chicago households;
  • Provided microbiome profiling services to eight studies led by CACHET members, including three funded by the CACHET Pilot Project Program;
  • Recruited Dr. Eric Pamer to assume Microbiome Core Leader position upon Dr. Gilbert’s departure;
  • With establishment of the DFI, CACHET launched a collaborative arrangement for DFI to assume the role of CACHET Microbiome Core, with a focus on translational EHS research;
  • DFI purchased four new state-of-the-art MS systems dedicated to microbial metabolite profiling;
  • Recruited Dr. Chaubard of DFI as CACHET Facilitator for Metabolomics Core, particularly for EHS research;
  • Established collaborative arrangements to leverage pre-existing and high-functioning institutional genomics and bioinformatics core facilities at UofC to augment the new BEES Sub-Core services for CACHET members; key services for CACHET investigators will be provided at “in-house” service rates with subsidized co-pay support available for justified EHS research.