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Pharmacogenetics Of Membrane Transporters Investigators


In response to an RFA issued by NIH in 1999, investigators at UCSF began planning for submission of a proposal for a large center grant focused on pharmacogenomics of membrane transporters. A multi-disciplinary team of investigators, led by K. Giacomini, I. Herskowitz and N. Freimer, was formed, which included pharmacologists, geneticists, computational biologists, statisticians and molecular biologists, individuals who before that time had never collaborated in a scientific endeavor. During initial meetings, the team decided that the goal of a large center such as PMT was to seed the scientific community with new information about transporter genomics and pharmacogenomics to enable hypothesis generation. In addition to genomic, functional genomic and genotype to phenotype clinical studies, one large phenotype to genotype clinical study, the Genetics of Response to Anti-depressants (GRAD), which focused on the SSRI anti-depressants, was proposed. A password protected transporter database was proposed, which subsequently developed into a public database, dbPMT. The first grant proposal was successful, and was followed by a competitive renewal, funded in 2005, which extended PMT until 2010. Studies funded by the competitive renewal, which are ongoing, have a major focus on noncoding region variants. Clinical genotype to phenotype studies began in the second round, translating laboratory discoveries to clinical studies of drug disposition and response.