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Update from the Dean - Spring/Summer 2015
By B. Joseph Guglielmo / Tue Mar 31, 2015
Dear UCSF School of Pharmacy Family and Friends:
As usual, there is much to report since I last wrote.
Our next strategic plan, Leading Change: Strategic Plan 2015–2020, is now complete, and our work is well under way. Five themes center upon our mission—research, education, and patient care—with a strong emphasis on our people and on the necessary framework for our success. While these themes may sound pretty standard, the details are anything but. A few of our objectives will give you an idea of the plans we envision:
- Design hybrid antimalarials that target disease while greatly reducing side effects … by taking advantage of a chemical reaction within infected cells that allows drugs to be deposited only into infected cells and not uninfected cells.
- Develop new drug leads for HIV/AIDS and cancer … by developing new methods to exploit human proteases.
- Improve efficacy, compliance, and safety of therapeutics for chronic and acute diseases … by engineering injectable and implantable nanoscale drug-delivery platforms.
- Devise computational methods to improve the design of drugs for neurodegenerative diseases … by defining and codifying the properties of molecules, allowing them to move more readily across the blood–brain barrier.
- Optimize a “big data” interpretive platform … by developing computational methods and integrated databases that predict drug action using multi-tiered datasets, and by developing computational methods to enable data-driven prescribing of drugs.
- Rapidly build 3D human tissues for basic research, regenerative medicine, and the study of cancer … by developing next-generation strategies for precise tissue fabrication from primary tissue or renewable cell stocks.
- Evaluate the economics of disease treatments … by using state-of-the-art comparative effectiveness and cost-effectiveness analyses of new technologies, drugs, diagnostics, and devices.
- Move forward seamlessly with PharmD curriculum transformation … by creating, supporting, and implementing structured curriculum design.
- Create core competencies shared by all UCSF health professions graduates … by collaborating with campus education leaders.
- Expand the unique interdisciplinary curriculum of School-administered graduate programs … by building new ties to the physical, engineering, and therapeutic sciences at neighboring institutions.
- Ensure that the UCSF health system’s accountable care organizations (ACOs) and other affiliations maximize the ability of patients to receive the right medications and take them the right way … by evaluating pharmacy care and medication management models in the ambulatory care setting.
- Interpret medication-related tests, including pharmacogenomics, to assess appropriate medication therapy for patients at UCSF Health … by creating a pharmacist consultation service.
- Personally connect our alumni with the everyday work of the School … by working with the Pharmacy Alumni Association to identify and pilot best approaches.
- Increase total giving to the School … by focusing our philanthropic work in the support of strategic goals and objectives.
You can find the full set of objectives in the detailed version of the plan on our website. Our strategic plan reflects our intention to lead the changes needed for patients to benefit from precise therapeutics used safely and effectively. The plan also serves as a solid foundation from which to launch even bigger initiatives. I welcome any and all comments on the plan.
For the second year in a row, all four UCSF schools topped the nation in federal biomedical research funding, and UCSF secured the second-most overall funds from the National Institutes of Health (NIH) for fiscal year 2014. For the 35th consecutive year, the School of Pharmacy ranked #1 among all schools of pharmacy with $31.8 million in grants, a total exceeding that secured by the next three schools combined.
You will notice that my research report highlights projects that support many of our strategic plan objectives.
Recently received research funding
Demonstrating a new method to detect, differentiate pancreatic tumors
Charles S. Craik, PhD, Department of Pharmaceutical Chemistry, received a two-year $380,000 grant from the National Cancer Institute to establish the feasibility of a non-invasive method to differentiate among different types of pancreatic disease and tumors—a vital step toward improving early detection and survival. Charly’s work draws on recent findings that certain proteolytic enzymes correlate with different stages of pancreatic cancer. The demonstration project will combine his lab’s protease activity probes with optical and radionuclide imaging of cancers in cell lines and animal models. The ultimate goal is a positron emission tomography (PET) imaging agent that provides non-surgical and improved early evaluation of pancreatic cancers.
Developing technology to print tissues with live cells to study breast cancer
Zev Gartner, PhD, Department of Pharmaceutical Chemistry, received a two-year $377,000 grant from the National Cancer Institute to develop a technology generating multi-cellular microtissues, within which the location of each cell can be specified. Working with co-principal investigators Adam Abate, PhD, and Russell Cole, PhD (a specialist in the Abate Lab), Zev will initially use precisely printed tissues, constructed from human mammary epithelial cells, to study estrogen receptor-positive breast cancer. The research will use a high-definition 3D cell printer to assemble large numbers of human breast microtissues with different and specifically defined compositions. He will subsequently explore which factors and neighboring cell types in the microenvironment regulate estrogen receptor expression. Beyond its experimental use studying individual cells, such technology may ultimately be used to print whole, functional tissues for organ replacement.
Applying microfluidics to sort, analyze B cells in autoimmune disease
Adam Abate, PhD, Department of Bioengineering and Therapeutic Sciences, received a five-year $2.4 million NIH Director’s New Innovator Award to develop an ultrahigh-throughput method for analyzing B cells of patients with autoimmune diseases such as rheumatoid arthritis and lupus, toward the development of more targeted treatments. Adam's new project combines his lab's hallmark microfluidics process with methods that enable him to analyze the genomes and RNA of millions of cells simultaneously. The microfluidic autoimmunoprofiling (MAP) developed by the Abate Lab will be used to sort out B cells that function normally (against pathogens) from those that inappropriately bind to self-antigens, resulting in an autoimmune response against healthy tissues. Such differences may not only enable discovery of new mechanisms underlying autoimmune diseases, but also serve as biomarkers for the disease-causing cells—allowing for more precise, safe, effective treatments.
Adam’s award marks the fifth year in a row that a School faculty member has received this highly selective New Innovator funding that supports, as the NIH notes, “a small group of exceptionally creative early stage investigators who propose bold new approaches that have potential to produce a major impact.” Prior awardees are Zev Gartner, PhD, 2013; Xiaokun Shu, PhD, 2012; Bo Huang, PhD, 2011; and Michael Fischbach, PhD, 2010.
Determining effective malaria prevention regimens in vulnerable populations
Francesca Aweeka, PharmD, Department of Clinical Pharmacy, received a five-year $3.4 million grant from the National Institute of Allergy and Infectious Diseases to study the safe and effective dosing of a recently introduced drug regimen aimed at preventing malaria in the most vulnerable populations—young children and pregnant women in Africa. Older drug combinations have been severely compromised by drug-resistant malarial parasites. The study, co-led by Philip Rosenthal, MD, of the School of Medicine, will analyze how a newer drug combination (dihydroartemisinin and piperaquine) is processed by young children and pregnant women and which dosing will maximize efficacy and prevent further resistance. This research leverages infrastructure developed in recent years in collaboration with Makerere University in Uganda.
Recent faculty publications
Developing drugs to treat the flu
William DeGrado, PhD, Department of Pharmaceutical Chemistry, is senior author of a paper in the Journal of the American Chemical Society that describes the design of urgently needed drugs against the flu. Bill’s work targets an influenza A protein involving the M2 proton channel—specifically, its membrane-spanning domain. Older drugs, such as amantadine, bind to sites in the M2 channel and block the passage of protons. However, the virus has developed a widely prevalent M2 protein mutation, known as S31N, which resists such drug binding. As a result, the Centers for Disease Control and Prevention has recommended discontinuing the use of these older agents. Bill and his team designed small molecules that bind to the most prevalent and problematic variants of the M2 protein and demonstrated that they disrupt the ability of the virus to reproduce. Potential impact: Optimization of these promising lead compounds could lead to development of durable flu treatments.
Discovering gene regulatory elements that are activated by drugs
Nadav Ahituv, PhD, Department of Bioengineering and Therapeutic Sciences, is senior author of a paper published in PLOS Genetics that identified gene regulatory elements in human liver cells activated by drug exposure and demonstrated a universally applicable method to detect such elements. Variations in genes and their associated proteins can affect drug activity, reducing efficacy or yielding toxicity. But variants in regulatory elements—specific segments of DNA that instruct genes when and to what extent to turn on or off—have been studied far less. Nadav and his co-authors looked for such elements genome-wide by analyzing liver cells treated with and without the antibiotic rifampin. Rifampin, like many drugs, is metabolized by cytochrome P450 (CYP) enzymes, specifically the CYP3A4 isoenzyme, which is thought to metabolize a large number of all pharmaceuticals. The researchers identified numerous specific rifampin-activated promoters (regulatory elements that jumpstart protein expression) and enhancers (elements that activate promoters). Potential impact: Finding gene regulatory elements activated by drugs is a first step toward correlating their variations with differences in drug metabolism. This could yield new pharmacogenomic tests to predict individual differences in drug response, thus guiding drug selection and dosing for greater safety and efficacy.
Determining real-world adherence to newer oral anticoagulants
Timothy Cutler, PharmD, Department of Clinical Pharmacy, is lead author of a paper published in the Journal of Managed Care & Specialty Pharmacy that analyzed whether patients prescribed dabigatran to prevent blood clots and strokes associated with atrial fibrillation were taking the drug as directed. The retrospective study of patients prescribed dabigatran for at least three months at UC Davis Medical Center (UCDMC) and affiliated clinics was coauthored by department colleague Tiffany Pon, PharmD, UC Davis faculty colleague Jennifer Branch, PharmD, and recent School graduates Alan Chuang, PharmD, and Tony Huynh, PharmD. Their study is the first to evaluate real-world patient adherence to this twice-a-day oral anticoagulant by comparing the electronic medical record with prescriptions actually picked up at pharmacies. This comparison yields an adherence measure, the Mean Possession Ratio (MPR), which divides the days of dispensed drug supply by the number of days elapsed until the next prescription refill. The MPR for patients taking dabigatran was 0.63, well below the authors’ threshold for adherence of > 0.80 and far below the > 0.95 MPR seen in clinical trials that evaluated the drug’s efficacy. Potential impact: The study findings suggest closer monitoring of patients on the newer oral anticoagulants and reinforces that adherence in strictly controlled studies does not necessarily translate to the real-world setting.
In my last Update I wrote that, under the direction of Vice Dean Sharon L. Youmans, PharmD, MPH, we were beginning the transformation of the School’s Doctor of Pharmacy (PharmD) curriculum. This transformation process is well under way, with full implementation anticipated for the class entering in 2017. A hallmark of the new curriculum will be the purposeful and strategic inclusion of interprofessional education and early practice opportunities. The curriculum is designed to build bridges—not just between health professions, but also between branches of science and between clinicians and patients. To leverage UCSF’s sole focus on health, our faculty is working closely with colleagues in the Schools of Dentistry, Medicine, and Nursing.
The new PharmD curriculum, the UCSF Bridges Pharmacy Curriculum, is a complement to the School of Medicine’s emerging UCSF Bridges Medicine Curriculum. As we build our unique requirements upon our medicine colleagues’ foundation, Sharon joins me in a commitment to the idea of “One UCSF.” Our combined forces will allow us to accomplish goals that would be impossible acting alone.
A steering group—aptly named the DRIVE Team (Design, Resources, Integration, Visioning, and Execution)—is coordinating the entire process and has recently created a curriculum project website. Visit the site for updates, determine how you can become involved, and view the list of faculty members moving the project forward [Note: the website is now retired]. Supporting our PharmD program are two new staff members: Celeste Nguyen, EdD, is the curriculum design and implementation manager for the Bridges Pharmacy project; Rebecca Miller, MS, is the new director of our Office of Education and Instructional Support. A warm welcome to both our new colleagues.
Update: The UCSF Bridges Pharmacy Curriculum Project is now known as the UCSF PharmD Curriculum Transformation Project: 2018 and beyond.
Robin Corelli, PharmD, and Betty Dong, PharmD, both Department of Clinical Pharmacy, were selected as fellows of the American Pharmacists Association (APhA), an honor that recognizes “exemplary professional achievements and service to the profession through activities with the APhA and other national, state, or local professional organizations.”
Charles S. Craik, PhD, Department of Pharmaceutical Chemistry, was named a fellow of the National Academy of Inventors, a status recognizing prolific academic innovators for inventions “that have made a tangible impact on quality of life.” Internationally known for his work on proteolysis, Charly holds 10 U.S. patents and co-founded Catalyst Biosciences and Alaunus Biosciences.
William DeGrado, PhD, Department of Pharmaceutical Chemistry, is the recipient of The Protein Society 2015 Stein and Moore Award, which recognizes “eminent leaders in protein science who have made sustained high impact research contributions.” In announcing the award, to be presented in Barcelona, Spain this July, the international organization noted Bill’s “bold body of work spanning decades,” and concluded, “His impact on the field of protein science can hardly be overestimated.”
Marcus Ferrone, PharmD, JD, Department of Clinical Pharmacy, was named the California Pharmacists Association (CPhA) 2015 Innovative Pharmacist of the Year. The award recognizes Marcus’ work developing and compounding a unique, specially labeled substance (hyperpolarized carbon-13 pyruvate) that enhances signal strength in magnetic resonance imaging (MRI) more than 10,000-fold. Detection of the injected drug’s uptake and metabolism by tumors has been used experimentally to evaluate the aggressiveness of prostate cancer and brain tumors (glioma), respectively, to guide treatment decisions and monitor therapy. International multi-site Phase 2 clinical studies are planned this year.
Jaekyu Shin, PharmD, and Marcus Ferrone, PharmD, JD, both of the Department of Clinical Pharmacy, and Matt Jacobson, PhD, Department of Pharmaceutical Chemistry, are recipients of the inaugural Dean’s Innovation in Education Awards. The new honor was established to recognize faculty members making innovative contributions to PharmD education:
Jaekyu transformed a second-year therapeutics course by delivering lectures and quizzes online, with class time used toward student case discussions emphasizing critical thinking and problem solving skills.
Marcus identified and adapted MyDispense software, which provides an online simulation to help students develop their competency at dispensing medicines and medical devices. It is now being applied in the first three years of the curriculum.
Matt revamped the first-year physical chemistry course content, introducing student-led presentations in which student groups analyzed and presented scientific papers focused on the physical principles underlying drug discovery and development.
Glenn Yokoyama, PharmD, is the recipient of the Academy of Managed Care Pharmacy 2015 Individual Contribution Award. This award represents Glenn’s longstanding dedication to furthering the profession.
New faculty members
Lei Wang, PhD, joins our Department of Pharmaceutical Chemistry. Lei earned a PhD in bioorganic chemistry from UC Berkeley and completed his postdoctoral training at UC San Diego, in the lab of Nobel Laureate Roger Tsien, PhD. He recently arrived from the Salk Institute for Biological Studies, where he received the NIH Director’s New Innovator Award. His research involves alteration of genes resulting in expression of proteins with unnatural amino acids. These proteins can be tracked or manipulated, such that cell signaling can be investigated in vivo toward the development of new medications.
We are pleased to announce our new web presence, including the following websites:
School of Pharmacy
Doctor of Pharmacy (PharmD) degree program
Department of Bioengineering and Therapeutic Sciences
Department of Clinical Pharmacy
Department of Pharmaceutical Chemistry
Faculty research lab, program, and center microsites
Be sure to calendar May 29 and 30 for Alumni Weekend 2015. For details, contact Rachel Katsuura, Director of Alumni Relations: 415-502-1887, [email protected].
A highlight will be the special School of Pharmacy history event in celebration of UCSF’s 150th anniversary year. It will be in Byers Auditorium, Genentech Hall, and you do not want to miss it! Our Pharmacy Alumni Gala Dinner caps the weekend, as we celebrate the awarding of the 2015 Distinguished Alumnus of the Year to Pamela (Salas) Schweitzer, PharmD ’87, by the UCSF Pharmacy Alumni Association, in recognition of her outstanding contributions to the profession, to society, and to UCSF. Pam is U.S. assistant surgeon general and chief pharmacy officer of the U.S. Public Health Service. She is also senior health insurance specialist for the Centers for Medicare and Medicaid Services and the Children’s Health Insurance Program, overseeing data systems. Our warm and well-deserved congratulations to Pam.
In addition, we will be celebrating UCSF’s 150th Anniversary Alumni Excellence Awardees at Alumni Weekend and throughout the year. The awards recognize alumni from across UCSF who represent the high caliber of our alumni community.
Ernest Prien estate
We are very grateful to our friend and alumnus Ernest Prien, BS ‘34, for his advocacy and generosity to the School during his lifetime and, as a founding member of UCSF Heritage Circle, for making plans for the School in his estate. Ernie died on September 1, 2013, at the age of 99. We recently received the final distribution of his total bequest of approximately $1 million, which Ernie designated as unrestricted, to be used by the School’s dean. I am in the process of carefully deciding its best use.
Ernie attended pharmacy school with a loan of $200 from a relative. He worked in Oakland immediately after graduation and then returned to his roots in Newman, California, where he purchased Pioneer Rexall Drug Store. Ernie was also the founder and retired chairman of the Synergex Corporation, formerly Digital Information Systems Corporation.
Always mindful of the help he had received early on, Ernie’s lifetime of philanthropy was in keeping with a man dedicated to helping others succeed. On behalf of the School, I am most thankful to Ernie for his foresight and for the success it will sow.
Mary MacWilliam estate
In 1992, Mary MacWilliam, EdD, established the Thomas William and Frederick John MacWilliam Memorial Fund (in pharmacology) with the intent of converting the fund to a distinguished professorship in the School. She also established several charitable trusts for the benefit of the endowment. Mary died in 2012 at the age of 95, and we are now in the process of finalizing the establishment of the distinguished professorship from Mary’s remarkable and generous bequest, which totals in excess of $1.5 million. The next step will be to name the holder.
Mary’s brother Thomas earned a pharmacy degree from our School in 1934. Her brother Frederick died in 1961, and Thomas died 10 years later. Mary pursued an undergraduate degree at San Francisco State and eventually earned a doctorate in education from UC Berkeley in 1956. She worked for more than 40 years as a librarian in the San Francisco State University Library. Mary’s gift is a lasting tribute not only to her brothers, but also to the power of education.
Update: Koda-Kimble Seed Awards bearing fruit
In 2012, the Joseph and Vera Long Foundation pledged $1 million to endow the Mary Anne Koda-Kimble Seed Award for Innovation, in recognition of Mary Anne’s distinguished 43-year UCSF career, including her 14-year term as dean of the UCSF School of Pharmacy. Additional generous donations from dozens of faculty, alumni, and friends have been made in support of this award, which is designed to fund “truly innovative projects that have the potential to move forward the mission of the School of Pharmacy in new ways.”
In December 2013, the first two projects were selected for funding; notably, both have now garnered additional or continued funding:
Faculty members Pamela England, PhD, and Matt Jacobson, PhD, both from the Department of Pharmaceutical Chemistry, and James Fraser, PhD, from the Department of Bioengineering and Therapeutic Sciences, received a $30,000 Seed Award to jumpstart a collaborative project using their labs’ complementary expertise to develop small molecule leads for drugs to halt the progression of Parkinson’s disease. I am pleased to report that their preliminary data was intriguing enough to generate an additional $25,000 in funding via the UCSF Clinical & Translational Science Institute (CTSI) Catalyst Awards as well as a $200,000 Bridging-the-Gap Award from the Rogers Family Foundation.
Graham Johnson, PhD, a principal investigator and assistant researcher in the Department of Bioengineering and Therapeutic Sciences, and Megan Riel-Mehan, PhD, a postdoctoral fellow in Graham’s lab, together received a two-year Seed Award of $46,220 to develop interactive software (cellPACK) for researchers to visually model systems biology information about cells at the mesoscale (10 to 100 nanometers). At this size, atomic details are too small to resolve by microscopy and too large and heterogeneous to capture via structural biology methods like X-ray crystallography and NMR spectroscopy. They plan to demonstrate their software’s utility by generating integrated 3D models with atomic-level detail of the mesoscale, spanning the entire life cycle of a bacterium. Not only did the project meet interim goals to earn its second-year seed funding, but it has also garnered an additional $40,000 gift from the Bio/Nano/Programmable Matter Group at Autodesk Research.
On the campus side, the pace has been dramatic. We opened the new UCSF Medical Center at Mission Bay, including UCSF Benioff Children’s Hospital San Francisco, UCSF Betty Irene Moore Women’s Hospital, UCSF Bakar Cancer Hospital, and UCSF Ron Conway Family Gateway Medical Building. The new facilities include a 289-bed hospital complex, with children’s emergency and outpatient services that will integrate research and medical advancements with patient care. Our faculty and our Department of Pharmaceutical Services colleagues worked as a team on the February 2 move-in day to help ensure that our transferred patients were medication-ready and safe. Imagine 40 ambulances, 300 faculty and staff, 100 emergency medical services personnel, and 131 patients in motion from 7:00 am to 3:30 pm. It was an exhilarating experience, and the true UCSF spirit of collaboration and shared focus on health ruled the day.
Our Mission Bay hospitals as well as our students, faculty, and neuroscience and aging research enterprises will soon benefit from the just-received gift of $100 million from Charles Feeney. He is the single largest contributor to the UC system, having donated more than $394 million to our campus. Generations of UCSF students, faculty, and patients to come will benefit from his tremendous generosity. Thank you, Mr. Feeney.
Effective February 1, long-time colleague Daniel Lowenstein, MD, follows Jeffrey Bluestone, PhD, as the next UCSF executive vice chancellor and provost. As Jeff returns to his research, Dan becomes second-in-command of our $5 billion enterprise. He is an exceptional scientist, administrator, educator, collaborator, and human being. Welcome, Dan, and thank you, Jeff, for your stellar service.
Another long-time UCSF colleague (and director of the California Institute of Quantitative Biosciences), Regis Kelly, PhD, was appointed by UC President Janet Napolitano as senior advisor on innovation and entrepreneurship effective December 1. He will promote and support innovation and entrepreneurship across the UC system. He is a seasoned and accomplished scientist who thinks big and outside the box, with the goal of maximizing the public benefit of UC innovations. This is an exciting aim for UC, and Reg is the perfect choice to move it forward.
As always, stay tuned.
B. Joseph Guglielmo, PharmD
Troy C. Daniels Distinguished Professor of Pharmaceutical Sciences
UCSF School of Pharmacy
About the School: The UCSF School of Pharmacy aims to solve the most pressing health care problems and strives to ensure that each patient receives the safest, most effective treatments. Our discoveries seed the development of novel therapies, and our researchers consistently lead the nation in NIH funding. The School’s doctor of pharmacy (PharmD) degree program, with its unique emphasis on scientific thinking, prepares students to be critical thinkers and leaders in their field.