Kathy Giacomini, PhD

What I do

My research focuses on membrane transporters, which are of great importance to drug disposition and response. I am particularly interested in genetic variants in membrane transporters that are determinants of drug response and in harnessing transporters to enhance drug targeting. 

My research expertise

Pharmaceutical sciences, Pharmacogenomics, Transporter Biology

Degree

PhD, Pharmaceutical Sciences, University at Buffalo (The State University of New York), 1979
BSc, Pharmacy, University of Houston, 1974

Biography

The Giacomini research group focuses on expanding our understanding of membrane transporters. Membrane transporters are of great pharmacological importance, as they play a major role in drug efficacy by regulating drug disposition and distribution. Major questions addressed in the laboratory include: What is the in vivo role of membrane transporters in drug disposition and response? How does genetic variation in membrane transporters affect clinical drug response? What is the endogenous role of membrane transporters? And, what are the structural determinants of specificity?

As PI of the NIH-funded Pharmacogenomics of Membrane Transporters project, Dr. Kathy Giacomini is leading an effort to determine the clinical implications of specific genetic variants in over 100 membrane transporters. Project ventures, ranging from basic discovery to clinical studies, have demonstrated that common variants of membrane transporters contribute to differences in drug response in ethnically diverse populations. Ultimately, these studies will increase our knowledge of the genetic basis underlying drug response, and will contribute to advancing the era of personalized medicine. Furthermore, our studies will elucidate the genetic mechanisms of decreased drug response and, ultimately, contribute to improving drug design for safe and effective treatments of subgroups of patients who do not respond to standard treatments.

Research in the laboratory focuses on drugs used in the treatment of diseases associated with metabolic syndrome. We are particularly interested in two key therapeutic agents, allopurinol, first-line medical therapy for gout and high uric acid levels, and the anti-diabetic drug, metformin, one of the world’s most widely prescribed drugs. In particular, our research focuses on discovering functional genetic variants that underlie variation in response to these drugs in large ethnically diverse patient populations. As a co-leader of the international MetGen consortium with over 10,000 patients from Europe and the U.S. on metformin, Giacomini and her collaborators are seeking to discover genetic factors that contribute to poor response to metformin. Importantly, her group is interested in understanding the molecular mechanisms responsible for metformin’s pharmacologic action. For allopurinol, we have discovered that genetic variants in membrane transporters contribute to variation in response to allopurinol. We are now seeking to understand the mechanisms through which the variants act on allopurinol response.

Finally, Kathy Giacomini and her collaborator, Russ Altman of Stanford University are the Co-PIs of the UCSF–Stanford Center of Excellence in Regulatory Sciences and Innovation (CERSI) funded by the Food and Drug Administration (FDA). Established in 2014, the UCSF-Stanford CERSI aims to advance the field of regulatory sciences and improve the development and evaluation of diagnostics, therapeutics and medical devices. The UCSF-Stanford CERSI is the first FDA funded CERSI on the west coast and seeks to address key challenges related to education and research that will advance the discovery and development of medical products.