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In Memoriam: William F. Trager (October 17, 1937 - November 24, 2009)

It is with great sadness that we learned that Dr. William Trager lost his brief battle with pancreatic cancer on November 24, 2009 at the age of 72. Bill was born on October 17, 1937 in Winnipeg, Canada and became a naturalized U.S. citizen. He received his B.S. in chemistry from the University of San Francisco in 1960, and his Ph.D. in medicinal chemistry from the University of Washington, Seattle, in 1965. His thesis research, under the supervision of Professor Alain C. Huitric, focused on the application of nuclear magnetic resonance to conformational analysis of drugs that contained cyclohexyl ring structures. Bill went on to do his postdoctoral research from 1965-1967 at the Chelsea School of Science and Technology in London, investigating alkaloid structures under the supervision of Sir Arnold Beckett.

In 1967, he joined the faculty of the University of California-San Francisco School of Pharmacy as an assistant professor of medicinal chemistry. While at UCSF, he acted as director of the high-resolution mass spectrometry center. Bill was one of the first to apply stable isotope labeling and mass spectrometry (particularly the then new technique of chemical ionization mass spectrometry) to studies of drug metabolism. Drug metabolism became the focus of his life’s research.

In 1972, Bill was recruited back to the UW School of Pharmacy to be a professor of medicinal chemistry where he served as chair of the Department of Medicinal Chemistry from 1980-1983. He also was appointed as an adjunct professor of the UW Department of Chemistry.

During his career, Bill Trager was an outstanding, encouraging mentor to 22 graduate students and 12 postdoctoral fellows. Most of his trainees are active researchers in academia, government research laboratories, and in the pharmaceutical industry. Several have won awards for their work, including three who have received scientific achievement awards, one from ISSX, one from ASPET, and one from SOT. Bill was well known by his students as an insightful scientist who excelled at encouraging others to do their best.

Over his career, Bill published ~200 research papers and co-authored books on drug interactions and on the chemical and enzymatic aspects of drug metabolism. He was internationally renowned for his work on warfarin metabolism and mechanisms of warfarin drug interactions, and one of his major achievements was to characterize some of the mutations of CYP2C9 involved in dysfunctional warfarin metabolism that could put people at risk of bleeding. Bill also was a pioneer in the use of pseudoracemates to identify and kinetically characterize isomers of drugs and their metabolites. Furthermore, he was instrumental in clarifying the theoretical basis for deuterium isotope effects in catalytic mechanisms of cytochrome P450 oxidation reactions. Bill was the principal investigator for nearly 20 years of a National Institutes of Health Program Project Grant investigating mechanisms of drug interactions. He received the Alumnus of the Year Award from the UW School of Pharmacy in 2001, and remained with the UW until his retirement in 2004.

Throughout his career, Bill was active in the International Society for the Study of Xenobiotics (ISSX), as an original charter member and Council member from 1986-89. He was invited to present at several ISSX and other meetings throughout the world, and organized the 4th International ISSX meeting held in Seattle, Washington, in 1995. He also attended several Drug Metabolism Gordon Conferences, contributing as a discussion leader and presenter to numerous conference symposia. Bill’s interests extended to chiral drug interactions, and he served as the editor of the journal Chirality for several years through the 90s, and also as a member of the Editorial Board of Drug Metabolism and Disposition from 1994-2002.

Bill’s scientific prowess opened the door for many scholarly appointments. He became science advisor to the Seattle district of the FDA, was a member of the Pharmacological Sciences Review Committee of the National Institutes of General Medical Sciences of the NIH, and served ad hoc on several NIH center and program project grants, as well as other grant committees.

Away from work, Bill enjoyed playing squash, golf and a little poker from time to time. On the squash court, he was an immovable force controlling the game from the center of the floor. On the golf course, control was rarely in Bill’s hands, but he loved the game nonetheless!

Bill was loved by his family, friends, colleagues and students. He was a man who was known for his sense of humor, collegial nature and keen intellect, but it is difficult to measure the full impact he had on all who benefited from his wonderfully warm smile and kind demeanor. We will always remember how genuinely welcomed he made people feel and how he always spoke of his family with pride and love.

The UW School of Pharmacy and the wider research community have lost a brilliant mind and a compassionate, kind soul. Bill will be sorely missed by all those who had the privilege of knowing him.

He is survived by his loving wife of 25 years, Caryl, and seven children from his blended family, as well as several grandchildren and one great-granddaughter.

Sid Nelson
Allan Rettie
December, 2009

For more about Bill Trager, or to post your remembrances of Bill, visit the School of Pharmacy home page.



Med Chem Welcomes New Grad Students.

The department is pleased to welcome Lucas Monkkonen and Natalie Garcia to our talented and dedicated group of graduate students this year.

Lucas Monkkonen comes to us from Grinnel College in Iowa. He was attracted to the UW because of the "fantastic research, great collegial atmosphere, and interesting mix of biochemistry, bioanalysis, and organic chemistry." He is especially interested in using instrumentation to increase his knowledge of protein biochemistry.

When Lucas is not studying, he's climbing mountains or playing piano and cello (but not at the same time). On the rare lazy morning, he indulges his taste for "unreasonable amounts" of bacon.


Natalie Garcia was an undergraduate student in the Molecular, Cell and Developmental Biology Department at UC Santa Cruz. She chose UW to "be surrounded by great people passionate about good science" who could inspire her to achieve her Ph.D. She is interested in protein chemistry (kinetic or structural) but is also open to intriguing possibilities in other directions.

Natalie enjoys playing piano, is a "huge movie buff," bikes the Burke-Gilman Trail, and swings a tennis racquet around "if the weather permits." (Hmmm. Someone forgot to tell her about our rainy winters....)

Welcome to Med Chem, Lucas and Natalie!



Dr. Alain Huitric Remembered.

Alain Huitric, professor emeritus of medicinal chemistry, passed away in late July at his home in Brittany, France, shortly before his 97th birthday. Read this tribute by former medicinal chemistry chair Bill Trager.



Med Chem Grad Student Publishes Book.

Graduate student Michelle Wahlin has written a book about the history of Sigma Delta Epsilon-Graduate Women in Science (GWIS). GWIS was incorporated in 1922; Michelle's book, 87th Year History, chronicles its colorful story.

Michelle was recruited to write the book by the GWIS via the University of San Diego's Department of Chemistry Chair, Dr. Tammy Dwyer. The 175-page book took a year to write; publication followed two years later.

"Writing this book was an amazing and unforgettable experience," said Michelle. "It gave me a unique appreciation for my opportunities as a woman in science, and for the pioneers that made these opportunities possible."

Congratulations, Michelle!



Congratulations, Med Chem Graduates.

Congratulations to the following students, who were awarded the Doctor of Philosophy in Medicinal Chemistry during the School of Pharmacy's June 12, 2009 commencement exercises:

Larissa M. Balogh
B.S. 2003, California State University, Long Beach.
Dissertation: "Stereochemical Complexities in the Glutathione S-Transferase Catalyzed Detoxification of 4-Hydroxynonenal."
(Dr. Balogh is now working for Pfizer in St. Louis, Missouri.)

Kevin J. Coe
B.S. 2000, Seattle University.
Dissertation: "Metabolism and Cytotoxicity of the Nitroaromatic Drug Flutamide and its Cyano Analog in Hepatocyte Cell Lines."
(Dr. Coe is currently a scientist at Johnson & Johnson in San Diego.)

Abhinav Nath
B.A. 2003, University of Virginia.
Dissertation: "Thermodynamics and Kinetics of Ligand Binding to Cytochrome P450 3A4 in Membrane Nanodiscs."
(Dr. Nath has taken a postdoctoral position in the Department of Molecular Biophysics and Biochemistry at Yale University.)

We are proud of our graduates and wish them the very best in their future endeavors!



Med Chem Staffer Attends Citizens' Academy.

"I like to call it 'Police Academy' but of course it's not," says Caryl Lynch, Med Chem staffer who recently completed the Spring 2009 session of the UW Police Department Citizens' Academy. Caryl is pictured here with Chief of Police John Vinson. The ten-week program, held annually on campus, allows UW students, staff, and faculty to learn first-hand about law enforcement at the University of Washington.

During the weekly sessions, officers and department personnel talked about their work. Subjects ranged from criminal procedure, weapons, and life on patrol to dispatching, evidence collection, and campus safety.

"It was a great introduction to all the ways in which the UWPD serves the University community, said Caryl, who is a Secretary Senior in Med Chem. "The discussions were fascinating. No question or concern was off-limits and the instructors were very open with us."

What was Caryl's favorite session? "I enjoyed meeting Chief Vinson and the officers," she said, "but my fave had to be Kali the K9 bomb dog and her specially modified police car!"



Med Chem Welcomes Jie Xing.

Dr. Jie Xing, our newest visiting scholar, joins Medicinal Chemistry via a 1-year award from the China Scholarship Council to pursue research in America. Jie Xing ("Jessie") is currently an associate professor in the School of Pharmacy at Shandong University, Jinan, China. She received her Ph.D. in Drug Metabolism and Pharmacokinetics from Shenyang Pharmaceutical University, China. Her work at Shandong University primarily involves drug metabolism and pharmacokinetics based on mass spectrometry. She is interested in expanding her research in proteomics, including quantitative description of protein expression and its changes under the influence of biological perturbations such as disease or drug treatments.

During her time at the UW, Jessie will work in Dr. Dave Goodlett's lab, researching protein structure analysis, specifically chemical cross-linking and mass spectrometry of multi-protein complexes followed by informatics analysis.

"I appreciate this opportunity to study and work with the outstanding scientists at the UW," said Jessie. "I believe everything here, including the people, the research atmosphere, and the beautiful campus, will make a deep impression on me. The knowledge and experience I gain will also benefit my future work."

"It is always a pleasure to welcome international scholars to our laboratory and to Medicinal Chemistry," said Dr. Goodlett. "Jessie will initially learn about our protein cross-linking approach and we hope she will help us to better understand metabolism and pharmacokinetics of artemisinin. As a bonus, she brings her experience on the LTQ-Orbitrap, which is a much used instrument for structure studies. We look forward to a fruitful year of study!"

Welcome to Med Chem, Jessie!



Med Chem Welcomes Kelly Lee.

Medicinal Chemistry welcomes Dr. Kelly Lee to the faculty. Dr. Lee comes to us from The Scripps Research Institute in San Diego, where he performed postdoctoral work at the Department of Molecular Biology.

Dr. Lee was awarded an A.B. degree in Physics from Harvard University, and a Ph.D. in Biophysics from Johns Hopkins University. Kelly’s postdoctoral work at Scripps involved biophysical studies of conformational dynamics in viruses. This is a continuing research interest for Kelly, who is conducting studies on several viruses including influenza, hepatitis B, and dsDNA bacteriophages.

Dr. Lee recently received a NIH Pathways to Independence Award from NIGMS for the study of: ‘Influenza hemagglutinin: structure, dynamics, and cooperativity during fusion.' He will continue this work at the UW. “I am excited to be joining this vibrant research and teaching community,” said Kelly. “The people are awesome, and I am eager to explore the possibilities for collaboration with other groups, to learn new things, discover how viruses tick, and find out how we can target them to shut down infections. I am also very interested in the adaptation or re-engineering of viral machines as protein therapeutic delivery devices. The broad research expertise in the School of Pharmacy makes this a great place to take this work forward.”

"Kelly brings a new dimension to research in the department, and we are very pleased to have been able to attract him to our School of Pharmacy," said Dr. Allan Rettie, Med Chem department Chair.

Welcome to Med Chem, Kelly!



Remembering Tom Kalhorn.

The School of Pharmacy mourns the loss of Tom Kalhorn, research scientist in the Department of Medicinal Chemistry's Mass Spectrometry Center. Tom died unexpectedly on March 2, two days after suffering an epileptic seizure.

Tom Kalhorn was born in Independence, Missouri -- a fitting hometown name for Tom if there ever was one. He received his BA in Chemistry and Political Science from Grinnell College in Iowa, and did some graduate work in Chemistry at the University of Kansas.

Tom's career with the UW began in 1983. He worked in Pharmaceutics as a research technician and lecturer until 2003, when he accepted the position of research scientist with Med Chem in the Mass Spectrometry Center. Some of Tom's important contributions to Pharmaceutics and Med Chem pertained to the Drug Interaction program project grant, where he prepared critical metabolite standards for drugs of interest. He introduced a stand-alone course on quantitative analysis methodologies and was a frequent contributor to departmental cumulative exams. He was known throughout and beyond the department for his analytical expertise and intelligence. His colleagues considered him a conscientious and capable teacher who gave selflessly of his time and expertise to benefit graduate students and post-doctoral fellows.

In addition, Tom Kalhorn had a unique personal style that made him beloved as well as respected. Who will forget his dazzling and varied collection of t-shirts: tie-dyed, brightly colored, or sporting pithy statements -- usually worn with shorts whatever the time of year? Tom touched a lot of people in Med Chem, Pharmaceutics, and beyond. He will be greatly missed.