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The Yale Center for Clinical Investigation (YCCI) was established in 2006 with the aim of providing broad support for clinical and translational research in today's increasingly challenging landscape. The time and money necessary to develop new drugs—it takes approximately 13 years at an average cost of $1.3 billion—mean that there is a clear need to accelerate the process of bringing new treatments to patients.1,2 Under the Clinical and Translational Science Awards (CTSA) and in alignment with the National Center for Advancing Translational Science (NCATS) mission to bolster translational science through collaborations that capitalize on existing strengths, Yale has invested strategically in research cores and built industry partnerships in an effort to speed up the development of novel therapies.3

One example is the Yale Positron Emission Tomography (PET) Center. In 2003, Yale and Pfizer, Inc., joined forces to establish a Bioimaging Alliance that would incorporate PET imaging into early-phase drug trials. Funds from the alliance provided the initial investment for Yale to construct and equip a 22,000 square foot PET facility at the School of Medicine, while Pfizer built a state-of-the art Clinical Research Unit two blocks away. The novel radiopharmaceuticals, high-resolution imaging, and quantitative analysis offered by the PET Center provide a rapid, accurate way to determine whether a drug candidate is reaching its target, enabling earlier decisions on whether to launch a clinical trial or to abandon a drug candidate before investing large amounts of money.

Along with Yale School of Medicine and Pfizer, YCCI has made substantial investments to bring the PET imaging program to the cutting edge of research expertise and technology. The PET Center boasts a technologically advanced radiochemistry laboratory housing a GE PET trace cyclotron to produce positron-emitting isotopes. It has one of the few high resolution research tomograph scanners in the world capable of brain imaging at a resolution of 2.5 mm, a state-of-the-art human PET/computed tomography system and three additional PET scanners for human and small animal imaging, as well as two fully equipped laboratories for blood and metabolite analyses and an image analysis laboratory. The Yale PET Center is free to carry out research supported by the National Institutes of Health (NIH) and other sponsors. Indeed, it has now collaborated with 10 pharmaceutical firms to evaluate novel drugs in preclinical and clinical studies. Accomplishments to date include the use of more than 25 PET radiopharmaceuticals for human studies and more than 65 for preclinical studies; the ability to perform awake brain PET imaging in nonhuman primates; the ability to visualize and quantitate small brain structures; the first use in humans of novel ligands for opioid receptors, serotonin transporters, and pancreatic beta cell mass; and methodological and clinical studies in diabetes, substance abuse, obesity, and Alzheimer's disease.

In addition to the PET Center, other Yale cores provide researchers with advanced technology not often found at academic institutions. For example, helped by CTSA funding, Yale's W.M. Keck Foundation Biotechnology Resource Laboratory offers genomics and proteomics services that range from oligonucleotide and peptide synthesis, DNA and protein sequencing, to gene and protein expression analyses using a constantly evolving array of state-of-the-art platforms. CTSA-funded Illumina microarray and Sequenom instruments have brought gene expression, single nucleotide polymorphism genotyping, and methylation analyses to bear on hundreds of biomedical research programs. An AB SCIEX (Framingham, MA, USA) TripleTOF 5600 mass spectrometer (MS), co-funded by CTSA and Yale School of Medicine, has enabled Keck to design a comprehensive workflow for liquid chromatography-MRM (multiple reaction monitoring) proteome assays. The highly effective YCCI/Keck partnership assisted more than 500 Yale investigators and nearly 600 non-Yale investigators at 300 different institutions in 2011.

Faced with a rapidly growing number of NIH-funded translational research projects that required high-throughput DNA sequencing, Yale took advantage in 2009 of its newly acquired West Campus to open a Center for Genome Analysis (YCGA) that is closely linked to Keck Laboratory. YCCI has been a key participant in developing YCGA, which is currently equipped with 10 Illumina sequencers purchased with a combination of NIH and institutional funds. This investment has led to exciting discoveries including mutations related to hypertension,4,5 congenital chloride diarrhea (one of the first published instances in which whole-exome sequencing was used to make a diagnosis)6, autism7, and melanoma.8

The strength of YCGA, together with the expertise of Yale investigators in the areas of signal transduction, genomics, and clinical cancer research, led in 2011 to a multiyear alliance with Gilead Sciences to accelerate the development of drugs for new cancer targets. Under the alliance, Gilead, a biopharmaceutical company based in Foster City, CA, will provide up to $100 million over 10 years to support cancer research at Yale, with the University maintaining ownership of intellectual property generated by the research and Gilead having the first option to license any discovery that it deems promising. A steering committee composed of scientists from Yale and Gilead oversees this highly focused effort. Results of DNA sequencing are analyzed by Yale scientists with the goal of defining new driver genes and mapping out the tumor-specific pathways and mechanisms related to cell proliferation, inhibition of cell death, metastasis, and drug resistance. The goal is to identify links in the chain that may be interrupted by new cancer drugs.

  • image(Figure)

[ Richard Carson, Ph.D., Director of the Yale PET Center, and a research team member—Photo credit: Robert A. Lisak. ]

Another example of building upon Yale's already strong research cores has been the merging of a long-time flow cytometry core in immunobiology with an immune monitoring core that was established several years ago with CTSA support. The ability to sort cells according to their molecular characteristics has revolutionized clinical and translational studies, because analyses can be carried out on virtually any cell that can be placed in a fluid stream, and purified populations of cells can be isolated for study and for use as therapeutics. Flow cytometry analysis has become widely used in clinical trials to monitor effects of immune modulators and markers of clinical response. Yale's flow cytometry core was historically used for basic immunology research, while the immune core was equipped for handling human cells, including clinical specimens. The combined core—which serves interacting research groups throughout the Medical Center—gives investigators access to a full range of instrumentation and expertise.

Leveraging resources—as well as partnerships among services and departments—is part of the Medical School's strategic plan and has led to unique tools such as the Research Accelerator, a novel platform for collaboration that was developed through pilot funding from the CTSA. The Research Accelerator is a secure website, free to all Yale users, that features a customized database for researchers to list resources, such as data, reagents, cell lines, antibodies, human samples, or transgenic animals. Using this site, Yale researchers can securely and efficiently find collaborators across disciplines and share data and resources listed by category, gene, pathway, and/or disease. This model can easily expand to include other CTSA sites and research partners.

At Yale, investments in research cores and tools, along with University-industry collaborations, are all part of a broad clinical research infrastructure that has been spearheaded by YCCI and aims to bring new treatments from the bench to the bedside as rapidly and efficiently as possible.

Acknowledgments

  1. Top of page
  2. Acknowledgments
  3. References

This publication was made possible by CTSA Grant Number UL1 RR024139 from the National Center for Research Resources (NCRR) and the NCATS, components of the NIH, and NIH roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH.

References

  1. Top of page
  2. Acknowledgments
  3. References
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