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Research Directions and Opportunities
Pharmacology is a rapidly changing discipline of growing importance in today's health care system. The main driving force for change in pharmacology is the rapidly advancing knowledge of the genetic code of humans and other species. With complete genomic sequences known for many species including humans, the focus of pharmacology is undergoing profound changes. Drug discovery based on genomic sciences has become a main focus of the pharmaceutical industry, while drug therapy consumes a rapidly increasing share of overall health care expenditures. However, drugs are effective in only a portion of patients, and often cause serious adverse effects. Pharmacogenetics-pharmacogenomics hold promise for improving drug efficacy and lowering adverse effects in individual patients. This will have profound and lasting impact in medicine. Therefore the use of genetic and genomics information to optimize drug therapy will be a central focus point for the Department of Pharmacology.
Numerous new drug targets will lead to a wave of drug discovery, exploiting the availability of genomic sequences of multiple organisms. Yet, discovery of novel drugs is insufficient to optimize future therapy. Biological complexity and interindividual variability are likely to limit therapeutic success. Medical genetics will reveal numerous variant genes predisposing an individual to disease. This will permit early treatment or even prevention of disease, requiring novel therapeutic strategies. Genetic variability among individuals will emerge as a major determinant of a patient’s response to drug therapy. Use of genetic information will promote individualized therapy. Computational biology will permit the modeling of complex systems, eventually leading to prediction of drug effects in vivo. Databases containing information on drug-gene/protein-effect relationships grow at an exponential rate; yet, the information contained in them is poorly utilized. Pharmacoinformatics is an emerging science geared towards mining the rich content of these massive databases for application to drug discovery and optimizing individual therapy. Translation of basic research findings into clinical applications is germane to effective therapies and has become a science in its own right.
To pursue these areas, the Department of Pharmacology focuses on the following areas.
- Pharmacogenomics. This program encompasses multiple areas: 1. Genetic information and genomic techniques aimed at drug target identification and drug design. 2. Use of genetic model systems to decipher mechanisms underlying disease and therapy (yeast, nematodes, zebra fish, mouse, etc). Specifically, genetically modified mouse strains have become important tools to understand gene function. 3. Pharmacogenetics and pharmacogenomics further address the interindividual variability of drug response, with the goal of optimizing therapy in individual patients. 4. Genes determining disease susceptibility and progression have the potential to guide drug therapy and facilitate early treatment and prevention.
The Program in Pharmacogenomics supports core facilities for microarray technology (mRNA expression arrays, proteome arrays) and detection of genetic variants. A main goal involves prospective SNP-genotyping to identify genetic variants that affect drug therapy. The Pharmacogenomics Program interacts with other genomics/ proteomics facilities on campus, programs in genetics, medical informatics, and clinical research units.
Cellular and Molecular Pharmacology. This field focuses on the molecular mechanism of drug action and the discovery and validation of novel drug targets. Emphasis areas include signal transduction, genomics and proteomics of membrane proteins (representing the majority of all drug targets). The program focuses on diseases, including neurological disorders and drug addiction, cancer, and cardiovascular-pulmonary diseases.
Neuropsychopharmacology. This program will focus on signal transduction pathways, drug-receptor interactions, in vivo drug studies in experimental anaimals (in particular transgenic animals), the use of functional genomics to understand mechanisms of drug actiona nd to discover novel drugs, and lastly, clinical research involving therapy of mental disorders. The Division of Neuropsychopharmacology (a possible joint venture between Pharmacology, Psychiatry, and other Departments) would provide an administrative structure to foster this enormously important area. Furthermore, it would encompass the CNS Focus Group fo the PiPGx. Importantly, it should integrate with a push for an Institute in the Neurobiology of Mental Disease, a possible emerging theme at OSU.
Functional Genomics, Computational Biology and Pharmacoinformatics. Functional Genomics serves to study complex biological systems - more broadly defined than Pharmacogenomics. Computational biology broadly encompasses structural biology, bioinformatics, and the modeling of complex systems. Drug design and the prediction of drug effects in a cell or even in humans will increasingly rely on theoretical approaches. Pharmacoinformatics takes advantage of the vast information in growing databases to predict therapeutic outcome and adverse drug effects. Moreover, it serves to design the most effective therapeutic strategies (selection of the type of drug and dosage regimen, early treatment or prevention). Increasing use of genetic information gleaned from pharmacogenomic studies or from the human genome sequence databases - in addition to clinical databases - will become a major component of pharmacoinformatics. This program integrates faculty in the Departments of Medical Informatics and Mathematics.
- Translational Therapeutics. In this field, scientists design clinical drug trials and monitor drug therapy using information gleaned from basic studies in molecular pharmacology, pharmacogenomics, medical informatics, pharmaceutics and related areas. Clinical studies increasingly exploit genetic information on susceptibility to disease and sensitivity to drugs. To assure effective linkage to patient care, a proposed Division in Translational Therapeutics will be jointly held across several Departments, Centers, and Colleges, providing research opportunities for basic scientists and clinicians alike.
- Clinical Drug Evaluation Phase I-II clinical trials are key to bringing a drug to the market. A Clinical Drug Evaluation division performs clinical trials specifically devoted to drug development. Studies are supported by contracts from the pharmaceutical industry. The division provides opportunities for clinical research and training in an area critical to the pharmaceutical industry.
- Division of Mathematical Biosciences (DMB) The explosion of research in the pharmacoogical sciences has created the need for new mathematical theories, statistical methods, and computational algorithms with which to draw knowledge from the rapidly accumulating data. The DMB catalyses interactions between the pharmacological and mathematical sciences through close collaboration with the Mathematical Biosciences Institute (http://mbi.osu.edu/) by participating in vigorous programs of research and education and nurturing a nationwide community of scholars in this emerging new field.