Environmental Factor, March 2008, National Institute of Environmental Health Sciences
UC-San Diego Superfund Researcher Honored with Gillette Award
By Melissa Fabiano
Former Superfund Basic Research Program (SBRP) scientist Kathy Senekeo-Effenberger, who worked in the laboratory of Pharmacologist Robert Tukey, Ph.D., at the University of California-San Diego (UC-San Diego), was awarded the James R. Gillette Drug Metabolism Best Paper of 2007. The award was presented by the Awards Selection Committee of the Drug Metabolism Division of the American Society of Pharmacology and Experimental Therapeutics (ASPET).
Effenberger was lead author on the paper, "Expression of the human UGT1 locus in transgenic mice by 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioactetic acid (WY-14643) and implications on drug metabolism through peroxisome proliferator-activated receptor ? activation," (http://www.ncbi.nlm.nih.gov/pubmed/17151188?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum) which was published in the ASPET journal Drug Metabolism and Disposition.
The Gillette Award is presented annually to authors of the two best papers published in Drug Metabolism and Disposition in the broad areas of drug metabolism and pharmacokinetics and disposition. The award honors the late NIH Pharmacologist, a scholar and scientist who demonstrated excellence in research. During his scientific career, Gillette published more than 300 papers and chapters, and co-edited seven books. He was considered a visionary and significant contributor to the field of drug metabolism and pharmacokinetics.
Effenberger's research supports the lab's examination of the role of nuclear receptors and cellular signaling events that regulate cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) genes. The Gillette Best Paper of 2007 focused on previous lab reports that demonstrated the in vivo control in animals of human UGT1A gene expression by xenobiotics, in addition to novel regulatory events that control expression of the human UGT1 locus. The animal models developed will allow researchers to understand the role of proteins in xenobiotic metabolism, and the potential mechanisms of adverse drug-drug interactions.
Jessica Bonzo, Ph.D., was Effenberger's colleague and a co-author of the paper. Bonzo, a UC-San Diego graduate, funded by the SBRP, now works for the National Cancer Institute Center for Cancer Research in Bethesda, Maryland in the Laboratory of Metabolism with laboratory chief Frank Gonzalez, Ph.D.
"This research article was the culmination of the effort of many people to characterize, in as much detail as possible, the influence of a widely used class of hyperlipidemia drugs on one of the major drug metabolizing enzyme families," Bonzo said. "It was a surprise to everyone involved in this effort...Kathy is very deserving as first author to be recognized for all her hard work. The paper only shows a small portion of the numerous animal studies Kathy performed in order to characterize this regulatory mechanism."
As part of this prestigious award, Effenberger will present her group's research at the Experimental Biology Meeting in San Diego, California (April 4-9, 2008) (http://www.eb2008.org/) on Sunday April 6th at the Drug Metabolism Division's platform session on Biotransformation and Drug Transport.
Currently, Effenberger is working for the clinical stage biopharmaceutical company Mpex Pharmaceuticals, which is involved in the development of new therapies to combat the growing issue of antibiotic resistance to gram-negative bacteria. In her work there, she hopes to expand her understanding of the risks associated with chemicals that are related to human health and the environment. She adds, "I would also like to gain experience and be involved with risk assessment, risk communication, and, ultimately, help in developing regulations and shaping public policies that will ensure [that] we can continue to protect and preserve our health and environment."
At the UC-San Diego Tukey Laboratory work continues to further characterize the cellular events that will lead to the regulation of the UGT1 locus. According to Effenberger, work continues on the recently developed Ugt1 null mouse model and its implementation to create a humanized UGT1 mouse model, which should help examine the regulation and role of human UGT1A proteins in vivo.