Scientific Report 2007

Scripps Florida

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Translational Research Institute

Departmental Overview

The Translational Research Institute merges drug discovery efforts at Scripps Florida with advanced technology platforms to rapidly identify and validate biological pathways that can be targeted for therapeutic intervention. The technology platforms are grouped into genomics, cell-based screening, and proteomics cores.

The goal of the drug discovery operation is to discover and develop small-molecule therapeutic agents for unmet medical needs in neurodegeneration, Parkinson's disease, acute respiratory distress syndrome, spinal cord injury, cardiovascular disease, cancer, and metabolic disorders such as insulin resistance and type 2 diabetes. Therapeutic areas and targets, which include G protein–coupled receptors, proteases, channels, and kinases, are selected on the basis of unmet needs and the ability to attract external funding. The drug discovery operation is fully integrated with the following groups: Lead Identification and High-Throughput Screening, headed by Peter Hodder, Department of Molecular Therapeutics; Medicinal Chemistry, headed by William Roush, Department of Chemistry; Discovery Biology, headed by Phil LoGrasso, Department of Molecular Therapeutics; and Drug Metabolism and Pharmacokinetics, headed by Mike Cameron, Department of Molecular Therapeutics.

The Lead Identification department enables drug-target lead identification via ultra-high-throughput screening technology. Using state-of-the-art automation and instrumentation, members in this department are responsible for developing and executing biochemical or cell-based high-throughput screening assays in a miniaturized 1536-well microtiter plate format. In addition to its support of internal Scripps Research objectives, the group participates in the National Institutes of Health Molecular Libraries Screening Centers Network, in which qualified assays are screened against the network's high-throughput screening compound library. Several internal and external investigators have accessed the department's expertise via collaborative or core-charge mechanisms.

The genomics core is headed by Mathew Pletcher. Scientists in this core oversee genotyping and gene expression profiling. The services provided by the core allow Scripps Research investigators to examine the genome at both the genetic and the transcriptional levels for the genes that underlie common diseases. In collaboration with Scripps Florida colleagues, members of the core have been involved in projects to identify the genes responsible for pathologic conditions, such as addiction and alcoholism, systemic lupus erythematosus, autism, obsessive-compulsive disorder, diabetes, obesity, and prion diseases.

The cell-based screening platform is headed by Julie Conkright, Department of Molecular Therapeutics. The faculty advisor to the core is Michael Conkright, Department of Cancer Biology. In this group, high-throughput technologies are used to provide a systematic description of the function of genes encoded by the human genome and a more comprehensive understanding of the genetic basis for human disease. Members of the group provide investigators access to genome-wide collections of cDNAs and short interfering RNAs that can be used to examine cellular models of signal transduction pathways and phenotypes.

The proteomics platform is headed by Jennifer Caldwell-Busby, Department of Molecular Therapeutics. The focus of this core is using liquid chromatography and state-of-the-art mass spectrometry technology to identify, quantify, and characterize proteins and protein modifications. Researchers in the core are involved in scientific collaborations in which novel technologies are used to identify biologically important proteins and protein modifications. Large-scale differential analysis is being used to map the pathways related to insulin sensitization and adipogenesis. In other projects, chromatographic enrichment techniques are used to identify sites of phosphorylation and other posttranslational modifications. Researchers in the proteomics core collaborate with other scientists to create experiments that will provide meaningful mass spectrometric results.