Translational Research Support Core (TRSC)

The Translational Research Support Core (TRSC) promotes the goals of the Center for Environmental Health and Justice in Northern Manhattan (CEHJNM) by supporting our community partners and existing research projects and by fostering new interdisciplinary research on environmental health and justice (EHJ). The TRSC includes expertise and facilities at Columbia University (CU)’s Lamont-Doherty Earth Observatory (LDEO)—one of the central units of CU’s newly launched Climate School—and CU Irving Medical Center (CUIMC). CUIMC and LDEO provide cost-share support to the TRSC labs, which can therefore offer subsidized member rates

The TRSC offers a comprehensive array of sample collection, field, and laboratory services. The Core is co-directed by Drs. Steven Chillrud and Hui-Chen Wu. This joint leadership provides complementary expertise—Dr. Chillrud in environmental matrices and Dr. Wu in biological matrices. The TRSC labs are organized into two sub-cores. Dr. Chillrud leads the sub-core comprising expertise on collection and analysis of environmental samples (e.g., air, dust, water, soil, other matrices) and sensor-based data for external exposure assessment; Dr. Wu leads the sub-core comprising expertise on collection and analysis of biological samples (e.g., animal samples or human blood, urine, saliva, hair, nails, tissues, cells). All six labs perform cutting-edge sample analyses. TRSC services include:

• Consultations on sample collection methods and study design;

• Processing and archiving environmental or biological samples;

• Developing and validating new equipment, including integrated and continuous monitoring for ambient, indoor, and personal monitoring;

• Maintain and loan field equipment;

• Support community-based research and Community Engagement Core (CEC) activities;

• Respond to exposure emergencies;

• Train students, staff, junior faculty and fellows;

• Provide TRSC lab services;

• Coordinate outside services with partner labs.

Description of Lab Services

Environmental Exposure Assessment (EnvExposure) – Dr. Steven Chillrud

Environmental Exposure Assessment Lab Leader: Steven Chillrud, PhD
Environmental Exposure Assessment Lab Manager: James Ross

The EnvExposure Lab provides consulting and training for collection of airborne particulate matter, water, and soil samples and use of low-cost and/or research-grade continuous monitors for particles and gases. It specializes in both non-destructive analyses [gravimetric, optical, and X-ray fluorescence (XRF)], which are critical for expanding analyses on small mass filters, and magnetic sector high-resolution inductively coupled plasma mass spectrometry (MS-HR-ICPMS) analyses (elemental and lead isotopic ratios) that require destructive sample preparation. The EnvExposure Lab has increased the sensitivity of analyses to meet its users’ needs. For example, in response to groups using miniaturized, low-flow rate personal monitors, the lab supported the development of a shared instrumentation grant for a high-precision automated weighing facility and recently developed a method to measure particulate matter on gold foils that could be used with impactors with a limit of detection of 0.5 µg. Analysis of biological samples in this lab is limited to acidified digests of blood or autopsy tissues for lead isotopic ratios as a source indicator. For studies with sampling needs that cannot be met using the lab’s available equipment, the EnvExposure Lab can design and manufacture customized sampling equipment for ambient, home fixed-site, and personal monitors. Efforts to develop, build, and/or validate sampling equipment have enabled many CEHJNM-supported pilots and projects. Examples include multi-pump home indoor and outdoor air sampling equipment, personal monitors for a pilot project on subway occupational exposures, and enclosures to integrate multiple samplers or features (e.g., heated inlets, sound dampeners, wireless communication) into packages that can be left inside the home. We have also developed enclosures to allow ambient monitoring of black and brown carbon in high-humidity environments with wireless communications, both for a community-based project on traffic congestion and stroke (R21ES030093, PI: Hilpert) and for the Columbia World Project (CWP) effort to measure community-wide emissions of CO₂ and black and brown carbon (PI: Dr. Jack). These services are a major strength of the EnvExposure Lab, in addition to its provision of routine maintenance and cross-calibration for sampling and monitoring equipment.

Allergens and Bioaerosols (BioAir) – Dr. Matt Perzanowski

Allergens and Bioaerosols Lab Leader: Matt Perzanowski, PhD
Allergens and Bioaerosols Lab Manager: Adnan Divjan

The BioAir Lab oversees collection of dust and air samples and measurement of allergens and other bioaerosols. It also oversees collection of serum and exhaled breath as well as measurement of allergy and pollutant susceptibility-related biomarkers in these samples. The lab has facilities for filter preparation and extraction of dust and air samples for allergen measurement as well as a range of dust and air collection equipment available for use in ongoing and pilot studies. The lab supports many population-based observational and intervention studies. The BioAir Lab also provides sampling, extraction, and analytical capabilities for measuring allergens in dust and airborne particulate matter samples, including those from cockroach, mouse, and dust mite. In addition, the lab refines commercially available assays for these proteins to increase sensitivity. The lab has also focused on assessment of fungi in environmental samples using nucleic acid-based detection methods and has helped characterize domestic fungal exposure in >1,000 homes in New York City (NYC). These methods are being used to assess fungal exposure in an ongoing large-scale intervention in NYC public housing. In addition, the BioAir Lab can analyze serum samples for IgE, IgG, and IgG₄ antibodies for a wide range of proteins and can also customize assays for proteins that do not have commercially available assays. For example, the lab developed an assay for testing IgE and IgG antibodies to novel fungal allergens in the serum of asthmatic children based on fungi measured in home dust samples. The lab also focuses on measurement of serum biomarkers of susceptibility, such as club cell 16 (CC16), which is positively associated with lung function and inversely associated with modification of risk for airway inflammation with combustion byproduct exposure. The work of the BioAir Lab is directly in line with the Center’s emphasis on EHJ, as pest allergens and fungal exposures are key causes in the health disparities of asthma.

Trace Organics (TraceOrg) – Dr. Beizhan Yan

Trace Organics Lab Leader: Beizhan Yan, PhD
Trace Organics Lab Manager: Khue Nguyen

The TraceOrg Lab extracts, isolates, and identifies microplastics, nanoplastics, and organic contaminants and biomarkers [e.g., 8-isoprostane, hydroxyl-polycyclic aromatic hydrocarbons (PAHs), oxygenated PAHs, polychlorinated biphenyls, dioxins, harmane, organophosphate pesticides, per- and polyfluoroalkyl substances]. The lab has the capacity to isolate pollutants from both biological and environmental matrices, analyze the extracts by various types of mass spectrometry (MS), and provide data to characterize exposures as well as the environmental and health effects associated with those pollutants. TraceOrg Lab services include proposal consultation for choosing the appropriate exposure approach and lab analytical methods including for source apportionment data analysis, running pilot samples for future large proposals, developing novel methods for nontraditional samples (e.g., bisphenol A in meconium, nanoparticles in motor cortex), and training students to improve lab skills. The lab is a leader in refining established methods for better performance. In addition to maintaining superior MS capacity for biomarker analyses, the lab has introduced other instruments to better serve Center members. For instance, recent developments in smart miniaturized samplers, including in a U01 project led by Drs. Chillrud and Perzanowski (PRISMs project funded by NIBIB), are beyond the capabilities of traditional gas chromatography/mass spectrometry (GC/MS) methods. To meet the analytical challenge, a sensitive micro-fluorescence detector was added to the Qtrap liquid chromatography (LC) with tandem MS instrument (obtained through an NIH S10 grant). The new capability allows measurement of most PAHs in about 10 µg of PM_2.5 samples. This new method is also used by members from other NIEHS Centers—for example, Dr. Judith Zelikoff from NYU requested analysis of filter samples collected in Queens, NY.

Biorepository and Bioanalysis (BioRepAn) – Dr. Hui-Chen Wu

Biorepository and Bioanalysis Lab Manager:  Hui-Chen Wu, PhD

Biorepository and Bioanalysis Lab Manager: Irina Gurvich, MS

The BioRepAn Lab is an extensively used shared resource with the Herbert Irving Comprehensive Cancer Center (HICCC), thus fostering integration with other on-campus resources and economy of scale. Services include consultation on collection of biological samples including types of tubes, aliquots, and collection kits preparation; sample processing including serum, plasma, total white blood cells, and peripheral blood mononuclear cells; inventory and storage of samples, primarily blood, urine, and saliva; isolation of DNA/RNA with quality control measures; and distribution of samples both within and outside of CU. Currently, 380,800 individual products from 40,490 participants are stored in the freezers adjacent to the lab and in a 1,500-ft² environmental health sciences freezer farm located two blocks away that provides expanded sample storage and allows splitting of individual samples into two locations for enhanced security. The farm includes eight –20ºC, 27 –80ºC, and six liquid nitrogen freezers. All samples are barcode-labeled, and the sample inventory is maintained on a relational database currently being transitioned to OpenSpecimen. Other equipment includes four laminar flow hoods, five centrifuges, a QuantStudio 7 PCR system, a plate washer, and a BioTek Synergy HTX 96-well UV, color, and fluorescence reader. The BioRepAn Lab also performs several assays including ELISA for DNA and protein adducts of PAHs developed by Dr. Santella, as well as assays for which commercial ELISA kits are available, such as urinary isoprostanes and viral infection assays. Candidate SNP genotyping using TaqMan assays on a 384-well format and mRNA/microRNA expression analysis using TaqMan on 384-well plates or arrays are also available; while these are standard services, they are in demand by Center members and complement deep-sequencing services offered by our partner labs. The BioRepAn Lab constantly evolves to fit the members’ needs. For instance, it recently established methods for telomere length analysis and extracellular vesicle isolation, which are gaining increased members’ interest. The lab also refers investigators to facilities, both on and off campus, optimized for large-scale, cost-effective analysis of molecular features, such as single-cell sequencing and DNA methylation microarrays.

Untargeted Analysis (Untargeted) – Dr. Gary Miller

Untargeted Analysis Lab Leader: Gary Miller, PhD
Untargeted Analysis Lab Manager:

The Untargeted Lab has expertise in high-resolution MS capabilities for routine analysis of endogenous and exogenous metabolites in human metabolic pathways, as well as a broad range of environmental, dietary, and pharmaceutical agents. The lab was created as an addition to the well-established Irving Institute Biomarkers Laboratory(BML),which already houses 10+ mass spectrometers. The BML supports targeted analysis for Columbia’s CTSA, which is facilitating the integrationof the untargeted platforms into clinical research projects. The Untargeted Lab became operational in March 2021 when the Thermo Q-Exactive HF-X Hybrid Quadrupole-Orbitrap MS passed quality controland continues to expand operations as new instruments come online (December 2021, Thermo LC Exploris 240 Orbitrap MSbecame operational; February 2022, Thermo GC Exploris 240 Orbitrap GC-MS/MS, installation and quality control in process).Two types of columns on the LC ultrahigh-resolution MS platform, a hydrophilic interaction chromatography positive and a C-18 negative column, will be routinely used, allowing wide coverage of polar and non-polar metabolites.The GC Exploris 240 provides improved coverage of semi-volatiles, volatiles, and other lipophilic molecules. By not limiting detected analytes to those selected a priori, these approaches allow us to greatly expandsurveillance of environmental chemicals, detect new xenobiotic metabolites, and identify previously uncharacterized pollutants. This enhanced exposure data provides screening measures for environmental-wide association studies. Combined with advanced data extraction, measurement of >100,000 chemical signals in biological samples is possible. The Orbitrap systems are capable of very highresolutions forcompounds present in blood or urine at low (<1 ng/mL) concentrations, allowing detection and quantification of very-low-intensity metabolites from environmental exposures, including up to 1000 confirmed exposure biomarkers from environmental, commercial, and drug metabolites. A custom pipeline for metabolomics data processing, quality control, and common statistical analyses includes multiple R packages (apLCMS, xMSanalyzer, xMSpanda, xMSannotator, xMWAS, MetabNet) and Mummichog (Python package for pathway/network analysis). Standard bioinformatics tools (Bioconductors, Bowtie/Tophat/Cufflinks, Cytoscape, GSEA, MeV) are routinely used for omics and systems biology studies. TraceFinder (with deconvolution add-on) and Compound Discover 2.0 are available.

Multi-element Trace Analysis (METAL) – Dr. Kathrin Schilling

Multi-element Trace Analysis Lab Manager: Kathrin Schilling, PhD

Multi-element Trace Analysis Lab Manager: Ronald Glabonjat, PhD

The METAL Lab performs high-quality trace metal analysis of biological samples and has successfully participated in blind intercalibration programs. The facility houses numerous analytical instruments to assess aqueous and solid biological samples. The lab specializes in urinary and blood trace element analysis and speciation measurements. It performs a suite of solid-phase (e.g., tissue, nanoparticle) digestions using a CEM Mars 6 microwave apparatus for superior total trace metal analyses. With a Perkin Elmer NexION 350S ICPMS, the METAL Lab can perform high-sensitivity measurement of 30 elements in various biospecimens (e.g., urine, blood, tissue, vesicles). The lab also measures arsenic speciation in urine and blood samples using an Agilent 8900 ICPMS with SPS4 autosampler equipped with Agilent 1260 Infinity II Bio-inert high performance liquid chromatography (HPLC) system. It is one of the key laboratories in the country able to conduct these analyses with great sensitivity and performs routine urinary creatinine and specific gravity analysis. Dr. Schilling’s expertise in isotope metallomics and advanced instrumentation (Nu Plasma 3 Multicollector ICPMS, located at LDEO where Dr. Schilling is a major user of the facility) provides additional analytical techniques of metals and their isotopes (e.g., selenium, zinc, copper) in various biospecimens and environmental matrices. These high-precision isotope-ratio measurements (uncertainty of ±0.0005%) can revolutionize the assessment of metal exposures as well as biological responses at a molecular scale to mixtures of toxic metals.