Update from the Dean - Spring/Summer 2011

Timothy Cutler, PharmD, Department of Clinical Pharmacy, received the 2011 Albert B. Prescott/GlaxoSmithKline Pharmacy Leadership Award from the American Pharmacists Association. The award spotlights a young pharmacist who the association believes will become a significant leader of the profession. Among his many accomplishments, Tim co-led a partnership among 7 California pharmacy schools to train student pharmacists to teach seniors, health professional students, and prescribers about Medicare Part D.

(Objectives: Prepare our doctor of pharmacy students to be leaders and agents of change. Find new ways for pharmacists to help patients make the best use of medicines. Find ways to provide pharmacy care to underserved patients.)

Danica Galonić Fujimori, PhD, Departments of Pharmaceutical Chemistry and Cellular and Molecular Pharmacology, is a 2011 Searle Scholar. Her pharmaceutical chemistry department colleague Bo Huang, PhD, earned the honor in 2010. This prestigious award supports young, accomplished biomedical scientists who show great continuing promise. Bo is developing super-resolution optical microscopy techniques to enable researchers to "see" the macro-molecular details of health and disease playing out in cells. Danica is developing chemical probes that will help researchers better understand the function of enzymes that change the ways genes are expressed, and thus alter the behavior of cells in both health and disease.

(Objective: Create new research tools.)

James Wells, PhD, Department of Pharmaceutical Chemistry chair, received the 2011 Bristol-Myers Squibb Smissman Award from the Division of Medicinal Chemistry of the American Chemical Society. The award spotlights a senior scientist whose work has substantially affected the development of medicinal chemistry. Jim is known for the discovery and design of small molecules that trigger or modulate cellular processes.

(Objective: Develop small molecules that can probe biological processes and serve as therapeutic agents.)

Adam Abate, PhD, recently joined our Department of Bioengineering and Therapeutic Sciences as an assistant professor. His research passions include high-throughput biology using microfluidics. What is this? Imagine fitting the reactions of a huge warehouse full of test tubes into one test tube filled with billions of tiny droplets, each housing a chemical reaction. Then imagine using robots to quickly sort these droplets to isolate the results you want. Adam is also engineering proteins through what is called directed evolution. This means that instead of adding chemicals to experiments to manipulate atoms and molecules—as chemists traditionally do—he is using the innate tools within biological systems, in this case enzymes, to create new kinds of protein molecules. Adam earned an AB in physics from Harvard College, an MS in physics from UCLA, and a PhD in physics from the University of Pennsylvania. He then returned to Harvard for postdoctoral work in physics and engineering before accepting his UCSF appointment.

(Objectives: Amplify and integrate physics into our work to more deeply understand health and disease. Create new research tools.)

Sherilyn VanOsdol, PharmD, is now with our Department of Clinical Pharmacy as an assistant professor of clinical pharmacy and drug information expert. She earned a BS in molecular, cellular, and developmental biology from UC Santa Cruz and a PharmD from UC San Diego. Then she completed a general pharmacy practice residency and a drug information specialty residency at the University of Illinois Medical Center. Her focus is on medication safety, an area of critical importance to the UCSF Medical Center and our Department of Clinical Pharmacy's Medication Outcomes Center. As therapeutic regimens become more complicated and new technologies—such as robotic dispensing and electronic medical records—become more widely used, we see more research questions surrounding best practices for medication safety. We look to Sherilyn to help reveal many of the answers.

(Objectives: Minimize medication errors. Find new ways for pharmacists to ensure patients get the best use of medications.)

We welcome Kevin Rodondi, PharmD, as an associate professor in our Department of Clinical Pharmacy. A longtime volunteer member of the faculty before this appointment, Kevin is also an alumnus with well-honed pharmacy practice and business success in the therapeutics sector, including: vice president of corporate operations for OnCare, Inc.; vice president, clinical, for Consensus Health; co-founder, chief operating officer, and president of the National Oncology Alliance, Inc.; and vice president and general manager of McKesson Specialty Solutions Group. Kevin will be developing new models of pharmaceutical patient care for both inpatient and outpatient settings.

(Objective: Design and validate pharmacy practice models that improve patient health.)

Hilary Campbell, PharmD, is the California Pharmacists Association (CPhA) 2011 Student Pharmacist of the Year.

(Objective: Prepare our doctor of pharmacy students to be leaders and agents of change.)

Melissa Wheeler, MS, just began a year-long competitive fellowship offered by UCSF's Pathways to Careers in Clinical and Translational Research (PACCTR) program. She will be working in the UCSF School of Medicine Department of Pathology to test the hypothesis that by blocking a specific cytokine—CSF-1—mesothelioma tumors may become more susceptible to chemotherapy.

(Objective: Broaden our students' experiences in novel health care practice and research settings.)

Tien Ho, Lisa Lam, Hilary Campbell, PharmD, and Aimee Loucks, PharmD are the 2nd-place winners in this year's national Pharmacy and Therapeutics Competition, sponsored by the Academy of Managed Care Pharmacy (AMCP). Gina Marotto and Paul Huynh placed 2nd, and Daniel Luu and Joshua Chua placed 3rd in the Student National Pharmaceutical Association (SNPhA) Kroger Clinical Skills Competition.

(Objective: Prepare our doctor of pharmacy students to be leaders and agents of change.)

Cynthia Stephens was part of a group that received a Leveraging/Collaboration Award from the Food and Drug Administration (FDA) for their work educating physicians about the FDA's Expanded Access Rule and its public health importance.

(Objectives: Prepare our doctor of pharmacy students to be leaders and agents of change. Advance interprofessional learning.)

Kathy Giacomini, PhD, Department of Bioengineering and Therapeutic Sciences co-chair, is leading the UCSF arm of the largest and most comprehensive study to date of the interaction between prescription drugs and membrane transporters. Her work is part of a larger grant awarded to Optiva Biotechnology from the National Institute of General Medical Sciences within the National Institutes of Health (NIH). Kathy's team will profile 2,000 prescription drugs against key membrane transporters that take these drugs into liver and kidney cells. As we learn more about this journey, we will be better able to manage how these drugs are best used safely and effectively in patients.

(Objective: Discover genetic factors that affect therapeutic and adverse drug reactions.)

Vuk Uskokovic, PhD, a researcher in the Desai Lab, Department of Bioengineering and Therapeutic Sciences, received one of about 200 five-year Pathway to Independence Awards (i.e., K99/R00s) given annually by the NIH. Vuk will develop nanostructured biomaterials that have antibiotic and bone-repair properties. These "smart" biomaterials will be able to hold drugs and release them at an adjustable rate to treat osteomyelitis and other hard tissue inflammatory diseases.

(Objective: Apply nanoscience to the development of tools to diagnose and treat disease.)

Janel Long-Boyle, PharmD, PhD, Department of Clinical Pharmacy, received a contract from the NIH to develop ways to personalize the dosing of fludarabine, a potent anti-neoplastic agent with significant toxicities that is used to treat leukemias and to prepare children for bone marrow transplant. Her goal is to identify patient-specific factors that influence fludarabine drug levels in order to improve engraftment and reduce toxicity.

(Objective: Find new ways for pharmacists to help patients make the best use of medicines.)

In an invited commentary in the May 23, 2011 issue of Archives of Internal Medicine, Christine Cheng, PharmD, Department of Clinical Pharmacy and Joseph Guglielmo, PharmD, the department's chair, call for prioritization in prescription labels' increasingly long lists of adverse drug events (ADEs).

(Objective: Steer policy that affects health sciences research and health care.)

Kathryn Phillips, PhD, Department of Clinical Pharmacy, co-authored an analysis, published in the May 2011 joint issue of Journal of Oncology Practice and The American Journal of Managed Care, of the medical records for hundreds of breast cancer patients. The authors found that although the lowest-income women were less likely to get testing for the HER2 gene, which predicts responsiveness to trastuzumab (Herceptin), they were more likely to receive the drug. These results indicate that a key genetic test could be more consistently applied to assure that only women who are HER2-positive receive trastuzumab and that inappropriate use of this costly therapy is avoided.

(Objective: Use evidence to steer policy that affects health care.)

A study by Lisa Bero, PhD, Department of Clinical Pharmacy, and colleagues found that the Medicaid program is likely paying far more than necessary for medications and not offering patients the most effective ones available. The study, posted online June 16, 2011 in American Journal of Public Health, compared the Medicaid program's Preferred Drug Lists in 40 states against the World Health Organization's 2009 Essential Medicines List.

(Objective: Advance our understanding of health care decision making.)

A study in Annals of Emergency Medicine, August 2011, co-authored by Steven Kayser, PharmD, and Cathi Dennehy, PharmD, Department of Clinical Pharmacy, and research colleagues, found that improvements could be made in the management of patients taking the anticoagulant drug warfarin who are seen in and discharged from the emergency department (ED). Almost half of those tested did not have therapeutic blood clotting ratios, and this was largely unaddressed. Furthermore, recommendations for anti-coagulation follow-up were documented for only one in 5 patients. Drugs that had the potential to interact with warfarin were administered in the ED or prescribed in some cases as well. The authors make recommendations to minimize adverse drug events that could arise from these observations.

(Objectives: Minimize medication errors and adverse events. Steer policy that affects health sciences research and health care.)

Patrick Finley, PharmD, Department of Clinical Pharmacy, was the lead author of a study examining the economic impact of a pharmacist-managed depression program in Asheville, North Carolina. In collaboration with the American Pharmacists Association Foundation, Patrick and research colleagues established an employer-sponsored depression clinic, enrolling 151 patients during the 2-year study period. More than 80% of the subjects remained in the program for a full year, and the economic analysis revealed a savings in overall medical costs of about $500 per subject annually. Full results were published in Journal of the American Pharmacists Association, January/February 2011.

(Objective: Design and validate pharmacy practice models that improve patient health.)

Esteban González Burchard, MD, MPH, Department of Bioengineering and Therapeutic Sciences, and colleagues at Stanford, published a commentary in the July 14, 2011 issue of Nature, stressing the need to increase the diversity of the populations involved in studies that associate genes with disease risk and, potentially, drug response. 96% of the subjects in such studies conducted so far have been people of European descent, and the findings do not necessarily apply to the rest of the world's population. On August 22, 2011, Esteban and colleagues published a study in the online edition of Pediatrics examining the association between smoking and asthma. Children born to mothers who smoked while pregnant developed a more severe form of asthma 8 years after their birth. Because fetal tobacco smoke exposure was so significant, the authors suggested a way to improve health outcomes through targeted smoking cessation during pregnancy.

(Objectives: Make the promise of personalized medicine a reality. Steer policy affecting health care.)

Researchers at the National Bio-Organic Biomedical Mass Spectrometry Resource Center revealed how the addition of certain simple sugars (N-acetylglucosamines) to specific amino acids (serines, threonines) in the proteins of mouse embryonic stem cells are crucial to embryo development. In a study published on June 7, 2011, in Proceedings of the National Academy of Sciences, center director and Department of Pharmaceutical Chemistry faculty member Al Burlingame, PhD, and UCSF colleagues, identified specific locations on dozens of proteins in stem cell nuclei that are modified and regulated by addition of the sugars. Some of those proteins are so-called transcription factors that are vital to the cells' maintenance and self-renewal.

(Objective: Use sophisticated physical methods to reveal normal biological, as well as pathological, processes at the detailed molecular level.)

James Wells, PhD, has been probing allosteric sites on enzymes as potential drug targets. Though less prominent than the traditional active sites, these can nonetheless affect enzyme reactions. Jim and his colleagues used a site-directed chemistry technique he developed called disulfide trapping, or tethering, to do this work. Target enzymes and small molecule fragments were engineered to enhance binding at an allosteric site on a protein kinase, PDK-1, which is a target for potential cancer treatments. The research, published in Proceedings of the National Academy of Science, March 23, 2011, remarkably identified some compounds that could activate and others that could inhibit the enzyme from the same site. Matt Jacobson, PhD, also in the Department of Pharmaceutical Chemistry, was one of several collaborators with Jim.

(Objective: Use sophisticated chemical methods to reveal normal biological, as well as pathological, processes at the detailed molecular level.)

Research in the laboratory of Danica Galonić Fujimori, PhD, whom I profiled earlier, explored how an enzyme that confers antibiotic resistance in dangerous bacteria performs its task. Danica uncovered a unique process that could lead to selective ways to target this mode of resistance. Her paper was first published in Proceedings of the National Academy of Sciences on February 22, 2011.

(Objective: Use sophisticated physical methods to reveal normal biological, as well as pathological, processes at the detailed molecular level.)

Adam Renslo, PhD, Department of Pharmaceutical Chemistry, Small Molecule Discovery Center, collaborated with Nobel laureate Stanley Prusiner, MD, and colleagues at UC's Institute for Neurodegenerative Diseases, to chemically optimize the structure of a class of small molecules called aminothiazoles, which they discovered as potential drug leads for treating prion diseases (e.g., Creutzfeldt-Jakob disease in humans and Bovine Spongiform Encephalopathy in animals). Specifically, they modified the aminothiazole molecules so that they would better cross the blood-brain barrier. In findings published in Journal of Medicinal Chemistry, October 1, 2010, and featured in The Economist, March 3, 2011, Adam and research colleagues showed that in mice, oral administration of the improved molecules produced brain concentrations far higher than those needed for anti-prion activity in in vitro neuron cultures. Indeed, preliminary results suggest that the best of the aminothiazole molecules are effective at extending the lives of prion-infected mice.

(Objective: Develop small molecules that can probe biological processes and serve as therapeutic agents.)