Kathleen M. Giacomini, PhD
Research Interests
Research in my laboratory focuses on the roles of membrane transporters in drug absorption, disposition, targeting, and in clinical drug response. Recent studies have centered on the role of genetic variation in membrane transporters in therapeutic and adverse drug reactions. The laboratory was the first to clone and describe the human liver specific organic cation transporter, OCT1, which mediates hepatic uptake of many clinically used drugs, environmental toxins and chemical carcinogens. A key aspect of our research is to discover naturally occurring genetic variants in OCT1 and other transporter genes in ethnically diverse human populations. We have established a local cohort of 1000 healthy volunteers of broad ethnicity, who are stratified by their respective genotypes and then undergo pharmacologic testing with conventional therapies. The overall goal of these studies is to better understand the genetic factors that contribute to the substantial disparities in treatment outcomes among ethnically diverse populations.
Selected Publications
- Wilke RA, Lin DW, Roden DM, Watkins PB, Flockhart D, Zineh I, Giacomini KM, Krauss RM. Identifying Genetic Risk Factors for Serious Adverse Drug Reactions; Current Progress and Challenges. Nat Rev Drug Discov 2007; 6:904-916.
- Shu Y, Brown C, Castro RA, Shi RJ, Lin ET, Owen RP, Sheardown SA, Yue L, Burchard EG, Brett CM, Giacomini KM. Effect of genetic variation in the organic cation transporter 1, OCT1, on metformin pharmacokinetics. Clin Pharmacol Ther 2008;83:273-280.
- Cropp CD, Komori T, Shima JE, Urban TJ, Yee SW, More S, Giacomini KM. Organic Anion Transporter 2 (SLC22A7) is a Facilitative Transporter of cGMP. Mol Pharmcol 2008;73:1151-1158.
- Huang N, Agrawal V, Giacomini KM, Miller WL. Genetics of P450 Oxidoreductase: Sequence Variation in 842 Individuals of Four Ethnicities and Activities of 15 Missense Mutations. Proc Natl Acad Sci USA 2008;105:1733-1738.
- Hesselson SE, Matsson P, Shima JE, Fukushima H, Yee SW, Kobayashi Y, Gow JM, Ha C, Ma B, Poon A, Johns SJ, Stryke D, Castro RA, Tahara H, Choi JH, Chen L, Picard N, Sjödin E, Roelofs MJ, Ferrin TE, Myers R, Kroetz DL, Kwok PY, Giacomini KM. Genetic variation in the proximal promoter of ABC and SLC superfamilies: liver and kidney specific expression and promoter activity predict variation. PLoS One. 2009 Sep 9;4(9):e6942.
- Professor and Chair
-
Bioengineering and Therapeutic Sciences
Research Theme
Drug Metabolism and Transporter, Pharmacgenomics
Contact Information
- kathy.giacomini@
ucsf.edu - Phone: (415) 476-1936
- Fax: (415) 514-4361
- UCSF Mission Bay Campus 1550 Fourth St.
- Box 2911, Bldg 19B RH584
- San Francisco, CA 94143-2911
Other UCSF Affiliations
- PSPG graduate program
- Clinical and Translational Sciences Institute
- Institute for Human Genetics