by Emily Swartzlander
Through nearly 30 core laboratories available for shared use by health science investigators, The Ohio State University Medical Center and Ohio State’s Comprehensive Cancer Center provide researchers with cutting-edge technology and affordable, timely assistance. In a new research strategic plan, core labs play a central role in advancing Ohio State’s leadership position in cancer research and emerging biomedical sciences.
Steven G. Gabbe, MD, remembers working as a research fellow at Harvard University in the 1970s when investigators were left to fend for themselves.
“Everyone worked independently, and when you needed a new technology or a new way of doing research or new equipment, you were pretty much on your own,” says Gabbe, senior vice president for Health Sciences and chief executive officer of The Ohio State University Medical Center.
Today, top academic biomedical research centers like Ohio State and Harvard offer investigators access to an array of shared services and core labs that allows them to work faster, more efficiently and more economically. In the current fast-paced research environment, Gabbe believes shared resources are more than a luxury, they’re a necessity.
“Scientific research is so complex, and new techniques are created constantly,” he says. “When we hear about new techniques, we want to apply them immediately so we can stay at the cutting edge. Our scientists, especially new faculty, don’t want to spend months or years accumulating the technology and resources they need to get to the point where they can finally do their experiments.”
“Our shared resources directors and their staff are critical to our research success,” says Michael A. Caligiuri, MD, director of The Ohio State Universtiy Comprehensive Cancer Center, chief executive officer of the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James), and holder of the John L. Marakas Nationwide Insurance Enterprise Foundation Chair in Cancer Research. “They provide a level of expertise and excellence in their specialties that helps investigators better design their studies, employ complex, advanced technologies and analyze their results.”
More than half of the Medical Center’s 27 shared resources labs have been funded for more than 35 years by the Comprehensive Cancer Center’s National Cancer Institute support grant, and as such they are peer-reviewed every five years against rigorous international standards.
“Our number one concern is to develop the shared services that support the highest quality science,” says Michael Lairmore, DVM, PhD, professor of Veterinary Biosciences and associate director for Shared Resources at the OSUCCC-James. “The range of services we provide reflects the science that we do here and the needs of our investigators and research programs.”
The Behavioral Measurement Shared Resource, for example, supports investigators doing population studies. “Expertise is available for everything from how to retrieve data to how to accrue patients to a study,” Lairmore explains.
Using Core Labs to Fight Cancer
Michael Ostrowski, PhD, and Gustavo Leone, PhD, are no strangers to the shared resource and core lab facilities of the OSUCCC-James. They’ve been using them for years to help with their research on the PTEN gene and the role it plays in a variety of cancers.
Most recently, Ostrowski, who is professor and chair of Ohio State’s Department of Molecular and Cellular Biochemistry and co-leader of the Molecular Biology and Cancer Genetics Research Program at the OSUCCC-James, along with Leone and colleagues in the Microscopy Core Lab and the Transgenic Animal Facility, developed three strains of genetically identical mice, each of which had one of three specific PTEN mutations. Their study showed that each version functioned in a different way, and that each influenced cancer development to a different degree.
“What core labs do that we cannot do on our own is provide absolute experts in very defined techniques,” says Leone, associate professor of Molecular Virology, Immunology and Medical Genetics, and a member of the Molecular Biology and Cancer Genetics Research Program at the OSUCCC-James.
Ohio State’s facilities are much more affordable than hiring outside experts, and they allow for a faster turnaround time to receive data, Leone says. “It would cost us a fortune to do some of the gene profiling that we need to do,” he adds.
They’re also important as educational tools for undergraduate, graduate and doctoral students. “We are training the next generation of scientists at each level, and this is highly supported by Ohio State through the core facilities,” Leone adds.
As they continue with their research, Ostrowski says the core labs and shared resources will continue to be important. “Actually, I would say they’re going to be a more important part of our research now. We’re going to need the type of technology these facilities can provide, especially when it comes to gene sequencing.”
Similarly, OSUCCC-James researcher Ching-Shih Chen, PhD, a medicinal chemist in the College of Pharmacy, requires a range of specialized technologies for his research in anticancer drug design. Chen and his lab have developed two drugs, AR-12 and AR-42, that are now in phase I clinical testing at the OSUCCC-James. AR-12 inhibits two signaling pathways important in breast, colon, lung and prostate tumors; AR-42 is active against prostate cancer in animal models.
Developing these agents required analytical cell-sorting capabilities, microarray assays and toxicopathological evaluations of mouse models – shared resources that are an essential part of drug discovery.
Carlo Croce, MD, professor of Molecular Virology, Immunology and Medical Genetics, director of Ohio State’s Human Cancer Genetics program and holder of the John W. Wolfe Chair in Human Cancer Genetics, is director of the Microarray research lab and has used that facility and others in his own research, which focuses on the link between cancer and miRNAs, tiny molecules that control important cell functions.
In May, Croce and investigators at 11 other centers published a study in the journal Genome Research identifying new miRNAs that can be used as targets for drug development and pinpoints for possible new cancer-related proteins. To complete the published study, Croce and the team of researchers used the OSUCCC’s Leukemia Tissue Bank to study miRNA expression profiles in 3,300 human cancer samples and 1,100 healthy tissue samples.
Croce agrees that shared resources such as the Leukemia Tissue Bank help investigators conduct their work as efficiently and accurately as possible. “These facilities allow us to have very expert hands take care of specific aspects of the research,” he says.
Ohio State’s Core Research Laboratories
The Ohio State University Medical Center and Ohio State’s Comprehensive Cancer Center offer investigators nearly 30 core research laboratories. Below is a brief description of each, along with where to find them online:
Analytical Cytometry and Cell Sorting* – Helps researchers analyze and sort cell populations.
Atomic Force Microscopy – high-resolution microscopy, allowing users to visualize single biomolecules at nanoscale resolution without drying or coating them.
Behavioral Measurement* – Offers population-based data retrieval, personnel support and consulting on study patient accrual procedures, and data collection methodology.
Behavioral Phenotyping – Offers equipment and expertise for monitoring behavioral responses, including social interactions, learning, memory, anxiety and depression.
Biomedical Informatics* – Features sophisticated computing techniques for data retrieval and integration, imaging, simulation, medical informatics and computational biology.
Biorepository and Biospecimen* – Procures and provides malignant and normal tissues from solid tumors.
Biostatistics Core* – Assists researchers in creating, maintaining and analyzing data, developing methodologies, publishing results and identifying collaborators for grant preparation.
Campus Microscopy and Imaging Facility – Offers a full range of microscopes and support instrumentation for cell and tissue preparation.
Center for Knowledge Management – One of the nation’s most comprehensive repositories of global biomedical knowledge.
Clinical Research Center – Provides indirect financial support for aspects of clinical research, such as hospitalization, ancillary laboratory costs and key personnel.
Clinical Treatment Unit/Clinical Trials Processing Lab* – Supports phase I and phase II clinical trials by assisting with procurement, processing, storage and shipment of research specimens.
Clinical Trials Office* – Facilitates development and implementation of all OSUCCC-James clinical trials.
Comparative Pathology & Mouse Phenotyping* – Provides experimental pathology support to investigators who use animal models of human cancer.
Electron Paramagnetic Resonance – Offers magnetic resonance technology for detection, quantification and visualization of free radicals in biological systems.
Laser Microdissection Pressure Catapulting Molecular Analysis Facility – Allows high throughput sample collection and molecular analysis of laser-captured tissue material and blood vessels.
Leukemia Tissue Bank* – Provides central collection, processing and repository for leukemia tissue samples collected from Ohio State protocols.
Microarray* – Offers genomewide analysis of multiple genes, along with consultation, RNA characterization, microarray processing and data analysis services.
MicroMD – Serves as the nation’s first technologically integrated facility dedicated to developing therapeutic applications for biological microelectromechanical systems.
Microscopy* – Allows visualization of the subcellular organization of living cells and tissues and the ability to probe living cells or tissues longer and deeper without damaging samples.
Molecular Cytogenetics – Provides molecular cytogenetic technology and classical banded metaphase cytogenetics.
Nucleic Acid* – Provides instrumentation and expertise for DNA sequencing, genotyping, real-time polymerase chain reaction, RNA/DNA extraction, imaging and DNA synthesis support.
Pharmacoanalytical* – Provides investigators with systems for quantitation of analytes and identification of metabolites in biological matrices.
Pharmacogenomics – Supports intermediate-scale genotyping for use in clinical association studies. Available panels cover nearly 1,000 polymorphisms, including target genes implicated in cancer, cardiovascular and central nervous system disorders, drug metabolism and transport.
Proteomics* – Provides researchers with instrumentation, expertise and services needed to identify proteins, protein modifications and protein biomarkers in biological samples.
Small Animal Imaging* – Allows investigators to receive high-resolution imaging of small animals and provides analytical software support for quantitative image analysis.
Transgenic and Embryonic Stem Cell – Operates jointly with Nationwide Children’s Hospital to provide transgenic mice and related services.
X-Ray Crystallography – Provides equipment and computational resources for collecting single crystal macromolecular X-ray diffraction data to determine crystal structures of proteins and other macromolecules at atomic resolution.
Viral Vector Core – Accessible as affiliated core through Cincinnati Children’s Hospital Medical Center that offers research-grade retroviral and lentiviral vectors, stable producer lines and quality control testing.
*Shared resources funded in part by the National Cancer Institute Support Grant and subject to rigorous peer review.
Expanding Shared Resources
Ohio State’s research cores are already comparable to those at the top research institutes in the country, but it’s important for the University to continue to expand the services it provides to investigators, Gabbe says.
“We are responsive to our investigators’ needs,” he says. “You just can’t do science today unless you have access to a broad range of research cores.”
Two new shared resources are in development funded in part by the OSUCCC-James’ recently renewed NCI support grant: a Medicinal Chemistry Shared Resource co-developed with Ohio State’s College of Pharmacy; and a Nutrient and Phytochemical Analytic Shared Resource co-developed with the Ohio Agricultural Research and Development Center.
Clay Marsh, MD, Ohio State’s senior associate vice president for Health Sciences Research, says Ohio State’s shared resources will become even more critical to its continued success. University leaders are creating a research strategic plan as part of a larger strategic planning process, and core facilities play a large role.
“We believe that having outstanding core facilities allows us to create an innovation pipeline,” Marsh says.
A committee led by Chandan Sen, PhD, associate dean for Translational and Applied Research, is reviewing all of the Medical Center’s research core labs to make recommendations to include in the plan.
“We want to identify what more we need in order to build and grow these facilities and to understand the access points and tools investigators need,” Sen says.
“These shared resources are key as we develop P4 Medicine* at Ohio State,” Caligiuri says. “The faster and more precisely we can analyze tumors and other tissues on the individual level, the better able we are to customize therapies for each patient. This requires advanced technology and the unique knowledge and skills of our shared resources teams.”
* Health care that is predictive, preventive, personalized and participatory; see page 3 for details.
• The Ohio State University Medical Center and Ohio State’s Comprehensive Cancer Center operate nearly 30 core research laboratories available for shared use by health sciences investigators throughout the University. The labs give researchers access to cutting-edge technology and affordable, timely assistance.
• For thpast 35 years, more than half of the Medical Center’s 27 shared resources labs have received funding from the Comprehensive Cancer Center’s National Cancer Institute support grant, and as such they are peer-reviewed every five years against rigorous international standards.
• Ohio State University leaders are developing a research strategic plan as part of a larger strategic planning process, and core facilities play a large role in future expansion of the Medical Center’s and University’s research capacity.
from left: Steven G. Gabbe, MD, Michael Caligiuri, MD, Michael Ostrowski, PhD, Gustavo Leone, PhD, Carlo Croce, MD, and Clay Marsh, MD.