Kathleen M.
Giacomini, Ph.D.
Professor of Biopharmaceutical
Sciences, Cellular and
Molecular Pharmacology
and Pharmaceutical
Chemistry

Contact Information:
kathy.giacomini@ucsf.edu
Tel: (415) 476-1936
Fax: (415) 502-4322
1550 4th Street
Rock Hall, Room RH-584F
Box 2911

Links:
Pharmacogenetics
Clinical Pharmacology

Publications
Complete
Selected

Pharmacogenetics of membrane transporters

Kathy Giacomini's research group focuses on membrane transporters, which facilitate the flux of drugs and important natural compounds into and out of cells. Three major questions with respect to these transporters are addressed: What is the role of membrane transporters in drug absorption and disposition? How does genetic variation in membrane transporters affect clinical drug response? What are the structural determinants of specificity of membrane transporters?

As PI of the major project funded by NIH, Pharmacogenetics of Membrane Transporters, Giacomini is leading an effort to understand the implications of genetic variation in 25 membrane transporters on clinical drug response. Initial studies of the project have demonstrated that there are common variants of xenobiotic transporters that may be responsible for variation in drug response. Ultimately, the information obtained from these studies may be used before treatment to determine if an individual is likely to benefit from a particular drug or experience adverse effects and may even be used to design drugs to better treat subsets of patients who do not respond to standard treatments.

By mediating influx of efflux in tumor cells, many membrane transporters play critical roles in sensitivity and resistance to anti-cancer drugs. Giacomini and her colleagues seek to determine whether genetic variation in transporters contributes to variation in sensitivity and resistance to anti-cancer drugs. She is particularly interested in sensitivity and resistance to anti-cancer nucleoside analogs such as gemcitabine. Recently, she is collaborating with Drs. Tempero, Ko, Chen and McMahon to determine the mechanisms of resistance to nucleoside analogs in cancer.

Publications:
Evolutionary Conservation Predicts Function of Variants of the Human Organic Cation Transporter, OCT1. Y. Shu, M.K. Leabman, S.J. Johns, J. DeYoung, E. Carlson, T.E. Ferrin, I. Herskowitz, and K.M. Giaocmini. Proc. Natl. Acad. Sci. 100:5902-07 (2003).

Natural Variation in Human Membrane Transporter Genes Reveals Evolutionary and Functional Constraints. M.K. Leabman, C.C. Huang, J. DeYoung, E.J. Carlson, T. Taylor, M. de la Cruz, S.J. Johns, D. Stryke, M. Kawamoto, T. J. Urban, D.L. Kroetz, T.E. Ferrin, A.G. Clark, N. Risch, I. Herskowtiz, and K.M. Giacomini. Proc. Natl. Acad. Sci. 100:5896-901 (2003)

Functional Characterization in Yeast of Genetic Variants in the Human Equilibrative Nucleoside Transporter, ENT1. D.H. Osato, C.C. Huang, M. Kawamoto, S.J. Johns, D. Stryke, J. Wang, T.E. Ferrin, I. Herskowitz, and K.M. Giacomini. Pharmacogenetics 13:297-301(2003).

Localization of Human Equilibrative Nucleoside Transporters, hENT1 and hENT2, in Renal Epithelial Cells. L.M. Mangravite, G. Xiao, and K.M. Giacomini. Am. J. Physiol Renal Physiol 284:F902-10 (2003)