Investigators who are citing shared resources in publications should use the description of those resources below.
Biostatistics & Bioinformatics (Tor Tosteson, ScD, Director; Jiang Gui, PhD, and Jim Sargent, MD, Co-Directors)
Established in the 1970s, the Biostatistics core provides statistical consultation and analysis for all researchers within the Dartmouth scientific and clinical community. Specific services include study design, statistical review, and interim monitoring for clinical trial protocols; statistical design and expert collaboration for large-scale clinical trial and epidemiology studies; experimental design and specialized statistical methods for integrative biology and laboratory-based research; statistical data management expertise; and specialized statistical software support and hardware access.
The Bioinformatics core consists of a comprehensive suite of bioinformatics tools and other resources along with an expert and diverse staff to meet the needs of Dartmouth researchers conducting basic, translational and clinical research. Services include applied bioinformatics and data mining; computer programming and software engineering; database development and administration; and high-performance computing and systems administration. The Bioinformatics group works closely with Biostatistics, and the Information Technology group of Dartmouth Cancer Center.
Clinical Pharmacology (Lionel D. Lewis, MB, BCh., MD, Director; Darcy Bates, PhD, Co-Director)
Established in 1994, this core provides pharmacology support for basic, translational, and clinical research through a wide array of experimental therapeutics support services including a biological sample storage facility for a wide spectrum of biological specimens; bioanalytical services using HPLC-UV and/or fluorescence, and LC-MS/MS with ESI and APCI ionization sources; pharmacokinetic and pharmacodynamic (PK-PD) expertise in study design; PK and PK-PD data analysis/modeling using FDA standard and state-of-the-art software (WinNonLn Pro); PD research support including tissue culture, cytotoxicity and immunoblotting services, and a SpectraMax i3x multi-mode plate reader with dual injectors and immunoblot imaging capabilities; pharmacogenomics interpretation; expertise in clinical trial sample collection/receipt, processing, logging, storage, and shipping; and investigational research pharmacy services.
Genomics and Molecular Biology (Craig Tomlinson, PhD, Director)
Genomics (Fred Kolling, PhD, Co-Director)
Established in 2002, this core continues to evolve to meet the changing needs of its basic, translational, and clinical researchers for genetics and genomics support. Current services include experimental design consultations; RNA and DNA isolation and quality analyses; Illumina- and Affymetrix-based microarray platforms for mRNA expression profiling with whole genome microarrays, miRNA arrays, CGH arrays, CpG island arrays, and SNP analyses. Deep sequencing services include all forms of DNA and RNA library construction for Illumina, deep sequencing, single cell sequencing. Specialized Genomics equipment includes the Illumina NextSeq 2000, 10x Genomics Chromium, Illumina iScan, Affymetrix array scanner, two tetrad thermocyclers for 96-well and 384-well plates for QPCR, other thermocyclers for controlled bench-top reactions.
Bioinformatics services including deep sequencing analyses of exome and whole genome DNA, all forms of RNA-Seq, single-cell Seq, and genome methylation, etc. are carried out by Owen Wilkins, PhD. Microarray RNA expression analyses are carried out by Carol Ringelberg, MS.
CRISPR services including knockout cell lines, knock in cell lines, CRISPR screen support and amplicon sequencing are carried out by Elizabeth Sergison, PhD.
Mouse genotyping services are carried out by Carol Ringelberg, MS.
Molecular Biology (Christian Lytle, BS, Co-Director).
Established in 1994, this core provides molecular biology services and products to support basic, translational and clinical research. Services include: automated high throughput DNA Sanger sequencing, NanoString technology for quantitative RNA, and protein expression analysis, DNA fragment analysis for STR’s and RFLPs, a BioXP for the synthesis and assembly of long DNA fragments. Instrumentation for quantitative real-time PCR, and various digital and film imaging and analysis systems.
Immune Monitoring and Flow Cytometry (Jackie Channon Smith, PhD, Director, Dan Mielcarz, PhD, Co-Director)
Formed in 2010 as a merger of the former Immune Monitoring (established in 2002) and Flow Cores (established in 1991), this Core provides quantitative assays to identify and compare immune responses elicited through various experimental manipulations and services related to flow cytometry. Immune monitoring activities support both basic and translational studies, including human immune monitoring through peripheral blood cell subset phenotyping, including regulatory T cell phenotype, functional, and conversion assays. Also available are cytokine multiplex analysis of patient or animal plasma and of cell culture supernatants, IFNgamma ELISPOT, and Dye Dilution Proliferation Assay. Additional services include cell enrichment using magnetic beads, peripheral blood mononuclear cell, serum, and plasma isolation, cryopreservation, and storage in shared resource freezers. Flow cytometry services include access to advanced instrumentation, high dimensional data analysis, cell sorting, workstations for data analysis and training in the use of instruments and data analysis software. The core has the following flow cytometry instruments available for use: two 27-color Bio-Rad ZE-5 cytometers, a 5-laser Cytek Aurora spectral cytometer, a 17-color FACSAria III cell sorter, a 13-color Beckman-Coulter CytoFlex cytometer, a 10-color Beckman-Coulter Gallios cytometer, an 8-color Miltenyi MacsQuant Tyto cell sorter, three 8-color MacsQuant 10 cytometers, and a 6-color Sony SH800 cell sorter. For other immune monitoring needs, the core has the following instrumentation available for use: an Agilent Seahorse XFe96 Extracellular Flux Analyzer, a Bio-Rad Bioplex 200 array reader, and a Zeiss KS ELISPOT reader.
Irradiation, Pre-clinical Imaging, and Microscopy (Jack Hoopes, DVM, Director)
Irradiation, Pre-clinical Imaging (Karen Moodie, DVM, Co-Director)
Established in 2007, this core brings together preclinical imaging resources for translational research under one administrative structure. Current instrumentation and services include: a 7T small bore MRI on the Hanover campus; a 3T large bore MRI, a recently acquired 9.4T MRI for animal research, and CT and PET micro-scanners at Dartmouth Hitchcock Medical Center; and bioluminescence (Xenogen) and fluorescence (in-house constructions) optical and biomicroscopy ultrasound (VisualSonics) imaging systems located in the Borwell Research Building, Dartmouth Hitchcock Medical Center. With institutional support small animal imaging has been consolidated into a new much larger facility immediately adjacent to the animal vivarium located on level 3 of the Borwell Research building. This consolidation, currently in process, offers multiple benefits including (i) the cross-training of support staff in multiple techniques, (2) placement of a new 9.4T MR small bore scanner into a core facility where it will be accessible to a much larger group of investigators, (3) co-location of other small animal imaging instrumentation currently operating at multiple sites across the campus, and (4) adjacency to the animal vivarium. The consolidation of small animal imaging technologies is anticipated to increase substantially use by current and future translational research clients.
Microscopy (Radu V. Stan, MD, PhD, Co-Director)
The facility provides state of the art imaging instrumentation and analysis software along with training and expertise to ensure their proper and efficient use. Instrumentation and technologies available to users include: (i) Zeiss LSM800 AIRYSCAN confocal microscope, a point scanning confocal system with high sensitivity GaAsP detectors allows confocal imaging of live cells, fixed cells, and tissues. It has full stage environmental control (temperature, gas and humidity) and autofocus, allowing long time lapse experiments of live cells. The Airyscan 32-detector array allows super resolution imaging. The system is integrated by Zen software allowing 3-D reconstruction, co-localization, deconvolution and image tiling. (ii) PerkinElmer Vectra 3.0 Automated Quantitative Pathology Imaging System is a brightfield and fluorescence whole slide scanner with multi-spectral acquisition and spectral unmixing capabilities, allows highly multiplexed biomarker imaging on tissues sections and cells. (iii) Sartorius IncuCyte Zoom live-cell microscopy system for fluorescence and enhanced phase contrast microscopy suitable for high throughput and long-term studies of cell-cell interaction, cell proliferation, survival and migration. The system enables time-lapsed images and kinetic measurements from living cells over many days with up to six multi-well plates imaged independently. (iv) Olympus IX-83 ZDC2 CellTIRFTM microscope equipped for live-cell, time-lapse brightfield/DIC and 4-channel (405, 491, 561, 640nm lasers) total internal reflection (TIRFM) and widefield fluorescence microscopy. (v) Olympus IX73 Inverted Fluorescence Microscope: has a wide assortment of fluorescence filters and objectives allowing high quality image capture of slides/multi-well plates using immunohistochemistry (IHC) or fluorescence readily is achieved. Image analysis software hosted on appropriately powered workstations with cloud connectivity for high capacity storage provided by Dartmouth College: HALO3, Inform, Volocity, AutoDeblur, Image-J / Fiji. The shared resource also provides state of the art instrumentation for transmission and scanning electron microscopy, as well as atomic force microscopy and Raman confocal microscopy, housed in the Dartmouth Electron Microscopy Facility (director M. Guinel, PhD). Instrumentation avaiable: (vii) FEI Tecnai F20ST (200kV) field emission transmission electron microscope (TEM), equipped with an EDAX X-ray micro-analysis system, and a 4K Gatan digital camera with anti-drift buffering mechanism.
(viii) FEI Helios 5CX dual beam FIB-SEM system allowing high resolution electron and ion beam imaging, ion beam milling and automated imaging of biological samples for 3D reconstruction. The system is also equipped with three X-ray microanalysis detectors allowing elemental analysis of the specimens. (ix) WITEC CRM200 atomic force microscope and Raman confocal microscope. The facility has instruments for specimen preparation for transmission and scanning electron microscopy including ultramicrotomes (Leica UltracutUC6 and UC7), critical point dryer (Samdri-970), platinum/gold sputter coaters, Leica ACE 600 coater and OPC-60 Osmium Plasma Coater.
Mouse Modeling (Steve Fiering, PhD, Director; Jennifer Fields, BS, Co-Director)
The Mouse Modeling Shared Resource supports the generation and utilization of mice for modeling human disease. The Transgenic Service supports the use of genetically modified mice by members of the Dartmouth research community. We offer a wide variety of services that assist researchers in construct design and creation of novel transgenic mice. We also offer mice with a humanized immune system that allows our investigators a better way to study viruses and other human infections. The PDX Mouse Service supports the development and utilization of patient-derived xenograft models of cancer research.
Pathology Shared Resource (Gregory J. Tsongalis, PhD, HCLD, Director; Wendy A. Wells, MD, Co-Director)
Established in 2007, this core offers the collaborative expertise of sub-specialty pathologists and clinical laboratory scientists in a CLIA-certified, CAP-accredited laboratory and achieves a level of quality assurance (validation, performance metrics, utilization) that is mandatory if new biomarkers, imaging correlates, molecular targets and pharmacogenomic correlates are to be discovered. The Pathology Shared Resource is part of the Section for Clinical Genomics and Advanced Technology (CGAT) which is housed within the Department of Pathology and Laboratory Medicine (DPLM). In recognition of the ever expanding role of the clinical laboratories not only in clinical testing but also in its robust and successful translational research environment, the DPLM was given the entire 4th floor of the WTRB (25,500 square feet) which is home to our section for Clinical Genomics and Advanced Technology (CGAT). CGAT occupies some 20,000 sq. ft. within the DPLM and was created to provide faculty and staff from different backgrounds access to proteomic, genomic, cell therapy and biobanking expertise. The CLIA/CAP standards are essential to the support of clinical trials, biomarker discovery studies and the transition of research findings to clinical testing. CGAT consists of the clinical molecular diagnostics laboratory, cytogenetics laboratory, institutional biorepository, Pathology Shared Resource, and the EDIT (Emerging Diagnostic and Investigative Technology) Research program. The PSR has access to space, equipment, and expert staff within CGAT. There are 38 dedicated technologists (3 research histology FTEs, 5 research FTEs and 30 clinical molecular FTEs), four post-doctoral fellows, 2 lab supervisors, a research coordinator, lab manager, 4 assistant directors and director. Laboratory resources include: automated DNA/RNA extraction platforms, next generation sequencing technologies, high-throughput genotyping capabilities, real time PCR, droplet digital PCR, gel and capillary electrophoresis, microarray technologies for expression analysis and copy number variation, tissue array instruments, quantitative morphometric image analysis, immunohistochemistry, immunofluorescence, FISH, prospective tissue procurement, and digital spatial profiling capabilities. The services provided include access to a variety of molecular-based tools as well as research histology services (creation and interpretation of tissue arrays, quantitative morphometric image analysis for immunohistochemistry, immunofluorescence, and digital spatial profiling). A cell processing laboratory for the isolation/purification, manipulation, expansion and/or storage of cells derived from a patient's/subject's peripheral blood is available and intended for autologous reinfusion. An expanded suite of mouse and rat histology services is also provided.
Proteomics (shared resource agreement)
For routine proteomics analysis we outsource samples to the Taplin facility at Harvard or the UVM COBRE Proteomics Core. We continue to monitor this outsourcing of samples for mass spectrometry and have found the quality and efficiency of the services provided to be excellent. Dr. Scott Gerber, our proteomics scientist at Dartmouth is available to provide on-site consultations to CEHS investigators.
Trace Elements (Brian Jackson, PhD, Director; Tracy Punshon, PhD, Co-Director)
The Trace Element Analysis Resource specializes in low-level trace metal analysis and speciation in environmental and biological samples. We use inductively coupled plasma mass spectrometry (ICP-MS) for metals analysis and several "hyphenated" techniques that couple instruments together for speciation analyses of water, soil and biological tissue samples.