Fourteen on-site basic, clinical and general core services offer the latest resources for cutting-edge research support at The Research Institute.  Scientists are charged a users fee, creating a cost efficient way to keep state-of-the-art technology available to all faculty. • Biomedical Genomics Core • Biopathology Center Core • Biostatistics Core • Cell Line Core • Clinical Research Services • DNA Sequencing Core • Flow Cytometry Core  • High-Resolution Research Imaging Facility • High Throughput Genotyping and Sequencing • Morphology Core • Nucleic Acid Core • Research Informatics Core • Transgenic and Embryonic Stem Cell Core • Viral Vector Core

Biomedical Genomics Core

Director: Peter White, PhD

The Biomedical Genomics Core aims to provide our clients with the complete genomics analysis solution, from the initial steps of experimental design to the final steps of results interpretation and publication. Our services include experimental design, quality control of starting material (DNA or RNA), sample labeling, hybridization, image acquisition, data analysis and interpretation. The facility is planning on introducing new technologies in the near future, including the ability to offer our clients Agilent Technologies DNA microarrays (a cost effective and sensitive alternative to the Affymetrix platform, enabling simple custom array design), and we are currently exploring options for the introduction of a Next Generation Sequencing platform.

Currently our services include:

• Expression Analysis using the wide selection of GeneChip® expression Arrays enabling researchers to simultaneously monitor genome-wide expression profiles, including the gene, exon, genome, promoter and tiling arrays.
• Gene Regulation Analysis using the High density GeneChip® Tiling Arrays, offer a tool to explore genome functions including mapping transcription factor binding regions and promoter region analysis (ChIP-on-Chip), DNA Methylation and Origins of Replication studies.
• Whole Genome Analysis using the GeneChip® Mapping Arrays enable scientists to conduct large-scale linkage analysis, association, and copy number studies. The new Genome-Wide Human SNP Array 6.0 features 1.8 million genetic markers for the detection of both single nucleotide polymorphisms (SNPs) and copy number variants (CNVs).

The Biomedical Genomics Core has become nationally recognized and was recently awarded official “Certified Service Provider” status by Agilent Technologies, becoming the first and only academic laboratory in the United States to have achieved this status.

For consultation and advice on experimental design and how to use our services please contact:

Peter White, Ph.D.
(614) 355-2671

David Newsom
(614) 355-5252 Core’s Main Line

Biopathology Center Core
Director: Nilsa Ramirez, MD

The Biopathology Center Core, an important component of the Center for Childhood Cancer, serves as the only pediatric repository for pediatric solid tumor samples and is one of only two repositories for leukemia samples in the United States, Canada, and Australia. To date, more than 80,000 samples have been characterized and distributed to 250 pediatric cancer researchers throughout the world in the past five years. Because of the Biopathology Center Core, The Research Institute at Nationwide Children’s Hospital receives more grant funds from the Children’s Oncology Group than any other national program.

The Biomedical Imaging Team is an important component of the Biopathology Center Core that is responsible for providing imaging service in an effort to enhance biomedical research. The Biomedical Imaging Team also provides service for several national organizations associated with the Biopathology Center Core including the Children's Oncology Group, the Gynecologic Oncology Group and the pediatric division of the Cooperative Human Tissue Network. It is the goal of the Biomedical Imaging Team to generate a well-annotated clinical image archive of high quality whole slide images for education, pathology, and research.

Nilsa Ramirez, MD
(614) 722-5643

Biostatistics Core
Director: William Gardner, PhD

The Biostatistics Core provides assistance to researchers in study design, data analysis and interpretation of statistical results. For other services such as data entry, database design or data management services, the Core can provide advice on how to set up simple data management systems and provide a referral to the Research Bioinformatics Core if complex data management services are needed. Please note that Results sections for papers or abstracts, or Methods sections for research proposals, will still need to be written by the investigator.
 

Grace Wentzel, CCRP, Administrator

(614) 722-2650 

Cell Line Core
Director: Kim L. McBride, MD

The Cell Line Core processes human subject samples and provides the researcher with cell lines or DNA, appropriate for downstream applications in a variety of human and molecular genetic studies. Services include extraction of DNA from saliva or whole blood, creation of EBV transformed B-cell immortalized cell lines or fibroblast cell lines from skin biopsy samples, and DNA or cell line archiving. Additional tissue types may be processed on request. Samples can be provided directly to other related Cores (such as the Biomedical Genomic or High Throughput Genotyping Cores). The Core possesses a set of lymphoblastoid cell lines for use as normal controls in genotyping or gene expression studies. These Coriell samples include the North European CEPH subjects used in the HapMap project, which have a wealth of publicly available genotype and gene expression data. The Core can also assist investigators in the design of genetic studies on human subjects and biobanking.

Small volume samples for transformation: Blood samples can be difficult to obtain on children, and we frequently receive samples of only 1-2 ml. We have developed new protocols to handle samples of low volume and/or low WBC counts for lymphoblast transformation, with the expectation we can improve transformation in this difficult group from 90% up to 95%, to more closely match our success rate of optimal samples (currently at 98%).

The Biobank Human Control Resource:  The Cell Line Core currently has a control set consisting of a collection of CEPH (Centre d’ Etude Polymorphisme Humain) individuals of North European ancestry obtained by special agreement from the Coriel Institute.  This collection includes the parents of the trios used in the HapMap Project, plus some additional samples for a total of just over 100 individuals, all of European ancestry. We are in the process of establishing a Biobank Control Resource to expand this set in both numbers and ethnicity.  Our goal is to have up to 200 individuals of European and 200 of African American ancestry available. Other ethnic groups will be considered for collection if there is a need.

Kim L McBride, MD 
(614) 722-2848
_______________________________________________________________________________________________________

DNA Sequencing Core
Director: Robert S. Munson, Jr, PhD  

The DNA Sequencing Core uses ABI dye terminator sequencing technologies for routine sequencing of plasmid and PCR templates.  We also provide expert technical assistance in preparation of templates, trouble-shooting failed sequencing reactions, designing primers, and all other aspects of DNA sequencing. The facility currently operates an ABI 3130xl sequencer.

DNA sequencing services are requested through the Finch software interface. 

Routine data analysis is performed using the DNA Star Suite of programs on local desktops or with the Phred/Phrap/Consed package and GCG Suite available on a Sun server in the Institute.

New users should request an account and training from Hua Zhong.

Hua Zhong  (614) 355-3533

Robert S. Munson, Jr, PhD (614) 722-2778 Wexner Building  5th Floor (502)

Core Lab (614) 355-3538 Wexner Building 5th Floor (584)

In addition to traditional flow cytometry analysis the core also offers cell sorting services via the BD FACSVantage/DiVa sorter.   Flow Jo analysis software is also available on stand alone computers on both Macintosh and PC platforms.  Aside from the traditional cytometers the flow core lab also has a Bio-Plex luminometer as well as a Wallac 1420 plate reader both of which use a 96 well plate format for applications such as fluorometry, luminometry and photometry with UV absorbance.  Flow cytometry is continually expanding in its applications as a research tool.  Contact us to discuss what flow cytometry can do to help facilitate your research or visit the flow core website to learn more.

For LSR training and Luminometer training:
David Dunaway
(614) 355-2820
Research II Building- WA 4112 

For Cell sorting :
Cindy McAllister
(614)-355-3465
Wexner Bldg. - 3rd floor

High-Resolution Research Imaging Facility
Director: Louis Chicoine, MD

The High-Resolution Research Imaging Facility at The Research Institute provides comprehensive research imaging support services to faculty researchers throughout Nationwide Children’s Hospital. The facility provides state-of-the-art imaging capabilities that expand our ability to generate and answer difficult research questions and provide an important platform enhancing our translational research programs.

The facility is organized into imaging suites, each loaded with specialty equipment.

Nuclear Imaging Suite:

• GE eXplore Locus CT: This high-and-low-resolution CT is capable of revealing bone and hard tissue structure just above cellular level. It includes 3-D reconstruction software, providing an “anatomic map” of both bone and organ structure.
• GE eXplore PET/CT: While this equipment can be used as a low-level CT or as a PET scan, its value lies in its ability to perform PET and CT simultaneously. With this feature, users can get an “anatomic map” of bone and tissue structure, combined with functional metabolic data. Thus, investiga¬tors can better detect abnormally functioning tissues and malformations (such as tumors) and pinpoint their exact location in relation in the body.
• GE Workstation: Addressing the need for rapid imaging, the GE Workstation includes hard drive capacity to regenerate, within minutes instead of hours, the images captured by the machines in the Nuclear Imaging Suite.
• Faxitron X-Ray: This 2-D X-ray equipment provides high resolution digital imaging, instead of using standard X-ray film.

Ultrasound Suite:

• VisualSonics Vevo 770: This non-invasive ultrasound pro¬vides a simple method for viewing and quantifying extremely small physiological structures and for imaging living tissue and blood flow with near-microscopic resolution. Committed to the placement and utilization of truly state-of-the-art equipment and capabilities, we are upgrading to the VisualSonics Vevo2100 in 2009.

Bioluminescence and Flourescence Suite:

• Lightools Pan-A-See: This Lightools version provides outstanding tissue penetrance capability, can process multiple colors simultaneously, instead of one, and has the capability of generating 3-D whole-body fluorescence images.
• Xenogen IVIS Spectrum: This latest and most powerful version of the Xenogen IVIS product contains enhanced cameras and higher registration capabilities. In addition, it can register bioluminescence and fluorescence simultaneously.

Terri Shaffer 
(614) 355-0430
(614) 690-1348 (pager)

The High Throughput Genotyping and Sequencing Core provides sequence analysis for clinical applications and a variety of genotyping methods for research investigations.

Clinical Sequence Analysis: After identification of a causative gene for genetic disorder in an internal or external research lab, the core validates and offers sequence analysis of the gene under clinical standards and regulations.
 

High Throughput Genotyping: A variety of platforms are available for microsatellite or single nucleotide (SNP) analysis, depending on the number of loci and patients being analyzed.  Microsatellite analysis is performed using fluorescently-labeled PCR primers with electrophoreses and analysis on the Applied Biosystems (AB) Genetic Analyzers (3130 or 3730).  SNP analysis can be performed using the SNPlex^TM Genotyping System (Applied Biosytems, up to 48 SNPs per reaction), allele discrimination using TaqMan^R technology (Applied Biosystems Sequence Detection System 7900HT), or analysis by liquid hybridization on the Luminex 200 (up to 50 SNPs per reaction).  The core works with investigators to determine the best approach for the research project and the degree of analysis to be performed in the core vs. the investigator’s laboratory.  Array-based SNP analysis is available through the Functional Genomics Core.

Julie M. Gastier-Foster, PhD
(614) 722-2866

Morphology Core
Director: Nilsa Ramirez, MD

The Morphology Core Laboratory was established in 1997 and provides services in histology, electron microscopy, flow cytometry, and confocal and laser scanning microscopy.

The Histology section of the core provides basic services such as tissue preparation and embedding, paraffin block or frozen tissue sectioning and H&E staining.  The Core also provides additional services such as direct and indirect immuno-histochemical staining, serial sectioning, and special stains. 

Routine Electron Microscopy procedures such as fixation, embedding, sectioning and visualization are available. The electron microscopy facility is equipped with an Hitachi H-7650 transmission electron microscope. The TEM has two digital cameras to allow for image optimization.

The Confocal microscope in WX287 allows 3D examination of tissue, with 3D reconstruction of the z-stack images. Multicolor fluorescence images are acquired with 2 internal detectors and 8 detectors on the Meta system.   Other applications include Time Series image acquisition, co-localization, FRET analysis, ROI bleaching and orthogonal viewing of images. There is also a standard Zeiss Axiophot epifluorescent microscope with a Zeiss Axiocam digital camera attached to it. Single color, multiple color and bright field images may be captured using the digital camera. 

The PALM Microbeam Laser Dissecting Scope is located in WX 392. The PALM Microbeam works with a pulsed UV laser (337nm wavelength) that is coupled to a Zeiss 200M inverted epifluorescent microscope. The laser is capable of micro-dissection and micro-ablation of small particles with sub micrometer precision.

Cindy McAllister
(614) 355-3465

Wexner Building – 3rd Floor
 

Nucleic Acid Core
Director: Julie M. Gastier-Foster, PhD

The nucleic acid extraction core is part of the Biopathology Center and supports clinical trials that require high quality nucleic acids.  A variety of methods are available for nucleic acid extraction from blood, tissue, or buccal swabs.  Quality control to test the integrity of the DNA or RNA is performed at the investigator’s request.  Each trial or project is managed separately after discussion with the investigator regarding optimal collection methods and desired downstream applications.

Julie M. Gastier-Foster, PhD
(614) 722-2866

Research Informatics Core

Director:  Dave Billiter, PMP

The Research Informatics Core is a multidisciplinary informatics application development team dedicated to enhancing and expanding research through the scientific application of information management and informatics innovation.  The Core is an award winning, service-oriented group which possesses the following capabilities in these diverse areas:

• Custom Research computer application development
• Research Study database design and development
• Application Data Integration and Research data marts
• Research data mining and reporting tools
• Research expert systems
• Research image analysis
• Custom Software Architecture
• Research based informatics consulting
• Project Management

The Research Informatics Core functions within a proven methodology which emphasizes continued communication throughout the lifecycle of the engagement.  The methodology is focused on a complete understanding of expectations during all phases which provides a clear direction for our informatics core, in the end producing the optimal solution for each customer.

Heather Day
(614) 355-2891

Transgenic and Embryonic Stem Cell Core
Katrina Kelly
(614) 722-2680
Wexner – 4th Floor (W490)  

Viral Vector Core

Director: K. Reed Clark, PhD

The Viral Vector Core supplies recombinant adeno-associated virus (rAAV) and recombinant adenovirus (rAd) vectors of uniform quality to individual research laboratories. The core is a full-service facility, capable of generating vectors beginning with a cDNA sequence and ending with the synthesis and purification of gene transfer vectors that have passed rigorous quality control assays. The core now supports production of six rAAV vector serotypes (rAAV1, rAAV2, rAAV5, rAAV6, rAAV8 and rAAV9), and offers retroviral gene transfer vectors through a collaboration with the Viral Vector Core at Cincinnati Children’s Hospital Medical Center.  The Core is in the process of building a Good Manufacturing Practice (GMP) production facility for manufacture of clinical-grade rAAV vectors.  Facility construction will be completed in the first quarter of 2008.

Andy Moreo
(614) 355-3464

Wexner – 3rd Floor (W350)

Link: Cincinnati Childrens VVC

Link: Viral Vector Adenovirus Request Form

Link: Viral Vector AAV Request Form