William J. Jusko Receives the 2020 AAPS Distinguished Pharmaceutical Scientist Award for His Work in PK/PD
By Mark Crawford
Shortly after receiving his Ph.D. in pharmaceutical sciences from the State University of New York (SUNY) at Buffalo in 1970, William J. Jusko joined its faculty and began his career as an educator and researcher. Now, 49 years later, he continues to teach at SUNY-Buffalo and make groundbreaking discoveries.
Jusko has focused much of his research on pharmacokinetics and pharmacodynamics (PK/PD). Early in his career he established a laboratory and program at SUNY-Buffalo to develop applications of PK and therapeutic drug monitoring (TDM) in patient therapy. He assessed drugs such as digoxin, theophylline, phenytoin, and corticosteroids, studying how factors such as renal failure, liver disease, obesity, smoking, and age impacted drug disposition. “With the introduction of high-pressure liquid chromatography,” says Jusko, “we developed sensitive and specific assays for many corticosteroids such as prednisolone.
Studies of adrenal suppression and cell trafficking effects led to his proposal of a family of “indirect response models” in 1993. Many extensions of these models have since been added over the years to handle added complexities. PK/PD studies of corticosteroids revealed more intricate mechanisms involving receptor binding, altered gene expression, and changes in proteins, biomarkers, and physiologic responses in various tissues. He and his research team continue to explore new systems models, such as the physiologically-based PK (PBPK) and PK/PD of prednisolone and dexamethasone. For these and other achievements, Jusko received the 2020 AAPS Distinguished Pharmaceutical Scientist Award.
An Unplanned Career
Jusko never planned out his career—it was largely “serendipity and timely opportunities” that determined his professional progression.
“I attended pharmacy school after working during high school in a drug store, thinking that being a practicing pharmacist back in my hometown of Salamanca, New York, would be pleasant,” he remembers. “I was the first in my generation to attend college, money was tight, and I worked part-time throughout college and graduate school. I also worked at the Children’s Hospital of Buffalo during pharmacy school, which led me to my current sideline interests in pediatric research.”
Although never a top student, Jusko was keenly interested in research and had no difficulty finding interesting topics to explore. It was always difficult for him to write NIH grants where he had to lay out a hypothesis and series of experiments, preferring a “let’s see what happens” approach. “My strongest capabilities and successes have come from exploring how drugs work and recognizing simple and natural ways of explaining their actions with mathematical models based on a mechanistic premise. This has resulted in many publications pertaining to models in areas such reversible metabolism, indirect responses, receptor/gene effects, chemotherapy, circadian rhythms, drug interactions, and target-mediated drug disposition (TMDD). In each of these cases, these efforts were enabled and enhanced by the help of many excellent graduate students, fellows, and collaborators.”
Collaboration and Effective Science
Jusko is a firm believer in advancing science through collaboration. While independent work is usually a priority in academia, pursuing projects with others can greatly enhance capabilities, productivity, and the chances of making discoveries that vastly improve human health.
Collaborations are part of Jusko’s research model—nearly all his 650+ publications have students, fellows, and/or collaborators as co-authors. University faculty are expected to demonstrate mastery in their scientific fields with publications, grants, invited lectures, insightful reviews, innovative coursework, and accomplished trainees. These expectations can only be enhanced by bringing in technology, techniques, and opportunities offered by collaborations. “One’s effectiveness is easily multiplied through such interactive synergies,” he adds.
Complementing these research highlights are the opportunities to teach and train graduate students and post-doctoral fellows and interact with numerous collaborators. “They have all been very talented and essential partners in my research endeavors,” says Jusko. “Teaching in our graduate courses in the areas of PK/PD has often sparked new ideas and concepts, both for me and the students.” A special event the Department of Pharmaceutical Siences has sponsored for 26 years is post-graduate PK/PD modeling courses for visitors to Niagara Falls. “We have had opportunities to present this course on-site at various pharmaceutical companies in the U.S. and for various audiences in countries such as France, Poland, and China,” says Jusko.
Participation in scientific societies is also an effective and enjoyable way to build new collaborative research and funding opportunities. Jusko has served on numerous academic, industrial, NIH, FDA, and organizational committees throughout his career. Jusko is especially enthusiastic about AAPS, which has been his primary scientific and professional organization since it was formed in 1986. “I am member number 000133,” says Jusko. “I have attended nearly every fall meeting to visit with colleagues and alumni, give lectures and posters, participate in some committees, recruit faculty and students, pick up souvenirs from the display booths, enjoy the social activities, tour new cities and areas, and accept a couple of awards. I am tremendously grateful to receive the 2020 AAPS Distinguished Pharmaceutical Scientist Award. It is the capstone of my career.”
Future Research Plans
After nearly five decades of pharmaceutical research, Jusko still finds his academic career immensely satisfying and enjoyable, which he feels has contributed greatly to his research success.
“Work should be consuming in that your profession is much of your way of life—your identity—and it should be difficult to put it aside because it such a part of who you are,” he says. “I often get new ideas about my research or PK/PD modeling issues while jogging or hiking or dreaming. Coupled with such innate enthusiasm is the need for cultivating professional friendships, alliances, and collaborations.”
In his free time, Jusko enjoys long beach vacations, especially in Hawaii and the Caribbean. During these trips, as well as other travels throughout the world, he has accumulated a collection of sand of many hues and colors from various beaches that he displays in old glass prescription bottles. Although he enjoys jogging and working out, his favorite exercise is maintaining the 30 acres of property at his countryside cabin near Salamanca.
Jusko is enthused about his current and future research plans and expects to make many more important PK/PD contributions, thanks to MIRA grant R35 GM 131800 from the NIH and his current research group. “Cortisol is considered the master hormone of the body and we are continuing to unravel the complexities of the diverse adverse and beneficial effects of its derivatives, the glucocorticoids such as dexamethasone,” says Jusko. “We are also assessing other drugs that may synergize with dexamethasone to treat COVID-19 symptoms.” Jusko also continues to research drugs such as gemcitabine used for pancreatic cancer to develop systems models that account for complexities in molecular signaling mechanisms. “In addition, our lab continues to evolve more complex mathematical models, particularly regarding physiologically-based PK,” he adds.
Another important contribution Jusko is making toward the future of pharmaceutical sciences is mentoring young scientists and researchers. “I was greatly helped and influenced by mentors in my career and would like to assist students, fellows, and junior colleagues in the same way,” he says. Jusko started mentoring graduate students in 1972, early in his career, and has continuously advised B.S., Pharm.D., M.S., and Ph.D. students as well as post-docs ever since. “Research in the pharmaceutical sciences is an integral part of developing new drugs and its future depends on maintaining a well-trained, curious, and innovative cadre of teachers and investigators,” says Jusko. “I benefitted tremendously by having mentors and I hope that my trainees will feel similarly when they look back on the time spent in my lab, office, and classrooms.”