2019 Koda-Kimble Seed Award supports School of Pharmacy’s boldest ideas

The UCSF School of Pharmacy 2019 Mary Anne Koda-Kimble Seed Award for Innovation marked its fifth year of funding with a March 5 announcement of award recipients by the School’s dean, B. Joseph Guglielmo, PharmD. The multiple awards will fund research into neuroscience, cancer treatment, and pharmacy education.

Applicants, who are all members of the School or teach in the School’s PharmD degree program, are encouraged to submit their boldest, riskiest, and most blue-sky ideas—those for which there is no ready or traditional source of funding.

The award has proved to be a fruitful way of funding research. Most recently, Department of Pharmaceutical Chemistry faculty members Pamela England, PhD, and Matthew Jacobson, PhD, who earned a Mary Anne Koda-Kimble Seed Award in 2013 to investigate a protein known to be involved in Parkinson’s disease, published evidence of the first known drug binding site on this protein.

As the School’s dean from 1998 to 2012, Mary Anne Koda-Kimble, PharmD, was relentless in her support for new directions in science, education, and patient care. The Seed Award for Innovation honors her legacy.

Nine projects, described in brief below, were chosen to receive 2019 Seed Awards and will share nearly $110,000 in total funding.

Disrupting chromatin recruitment by targeting reader domains

Principal applicant: Danica Fujimori, PhD, faculty member, Department of Pharmaceutical Chemistry

Award funding: $17,000

The project: In over half of cancer cases, a gene known as MYC goes into overdrive. The gene is also very hard to target, having few places to which drugs can bind. Fujimori believes that MYC could be throttled by preventing it from binding to the genome. She hypothesizes that small molecules could be used to target these binding sites, preventing MYC from gaining a foothold. In the long run, the results could have implications for treating human cancers.

Deep drug phenotyping with highly multiplexed single-cell RNA sequencing

Principal applicant: Zev Gartner, PhD, faculty member, Department of Pharmaceutical Chemistry

Award funding: $27,000

The project: Determining how cells change after being exposed to drugs is a slow, expensive process. Each experiment can only look at one factor at a time, such as growth or changes in drug resistance or disease phenotypes. Gartner believes that single-cell RNA sequencing (scRNA-seq) could fill the gap, allowing researchers to run thousands of experiments in parallel at an affordable cost. To this end, he is developing technology that reduces the cost of running 1,000 scRNA-seq samples from $1.35 million to around $20,000. He will use these new screening techniques to examine heterogeneous breast cancer cells for changes in gene expression when they’re exposed to drugs in the lab. The results will have implications far beyond just breast cancer, enabling scientists across fields to easily produce valuable data when evaluating potential drugs.

Student taught education in pharmacy (STEP)

Principal applicant: Leena Dolle, PharmD student, Class of ’21

Award funding: $3,500

The project: The School is restructuring its doctor of pharmacy (PharmD) curriculum, integrating courses and building content on a foundation of scientific thinking. With time and attention focused on curriculum content and new teaching and learning approaches, there was little room to develop a complementary teaching assistant program. This left a temporary gap in opportunities for current PharmD students to teach. Looking to the Oath of the Pharmacist for inspiration, Dolle wants to both “prepare the next generation of pharmacists” and encourage student teaching. In the STEP program, second-year students will host weekly content reviews of difficult concepts taught to first-year students, starting with students in the Class of 2022.

Elucidating the metabolic response to targeted therapy in lung cancer cells

Principal applicant: Karl Kochanowski, PhD, postdoctoral researcher, Department of Pharmaceutical Chemistry

Award funding: $15,000

The project: Drugs known as tyrosine kinase inhibitors have become popular candidates for treating various cancers, but despite their effectiveness early in treatment, tumor cells often become drug resistant within twelve months. Early attempts to overcome this drug resistance involved the study of alternative signaling pathways, but there is evidence that cancer cells may also change their metabolic state to avoid drug toxicity. Kochanowski plans to monitor the metabolism of cancer cells as they are exposed in the lab to tyrosine kinase inhibitors, tracking the concentrations of hundreds of metabolites at once. He will then use this information to test how the disruption of various metabolic pathways could be used to stymie the development of cancer cell drug resistance.

A characterization of APPE readiness by faculty, preceptors, and students

Principal applicant: Katherine Gruenberg, PharmD, assistant professor, Department of Clinical Pharmacy

Award funding: $1,685

The project: The transition from classroom-based learning to experiential learning is one of the most important aspects of pharmacy education. Assessment of student preparedness to embark on these advanced pharmacy practice experiences (APPEs) is required by the American Council for Pharmacy Education. However, traditional metrics of preparedness, like standardized examinations, may not comprehensively address all aspects of emotional and cognitive readiness required for successful clinical learning. Gruenberg will coordinate a series of focus groups with pharmacy faculty, preceptors, and students to describe characteristics needed for student APPE preparedness.

In vivo imaging of Par3-Par6-aPKC complex in the asymmetric dividing neuronal progenitors

Principal applicant: Xiang Zhao, PhD, postdoctoral fellow, Department of Bioengineering and Therapeutic Sciences

Award funding: $7,500

The project: Embryonic brain development depends on the coordinated multiplication and diversification of stem cells. One way that stem cells ensure their own reproduction, as well as the production of mature cells, is called asymmetric cell division (ACD). In ACD, one stem cell divides to produce one additional stem cell and one maturing, or differentiating, cell. This process has been well studied in fruit flies and nematode worms and linked to the movement of cell polarity proteins during cell division. However, this movement of proteins during ACD has not been well documented in vertebrates. Zhao will use live imaging of the growing zebrafish embryo to track the movement of some of these proteins in dividing neuronal stem cells, work that will shed light on how the complex brains of vertebrates form.

A novel fentanyl testing kit and harm reduction initiative at San Francisco Veterans Affairs Health Care System

Principal applicant: Tessa Rife, PharmD, San Francisco Veterans Affairs Health Care System; volunteer faculty member, Department of Clinical Pharmacy

Award funding: $5,750

The project: Drug overdoses are a national health emergency. In 2017, nearly 20 percent of opioid overdose deaths in California were due to fentanyl, a powerful opioid analgesic that is often illicitly manufactured and mixed with other drugs. Rife is starting an education program for patients engaged in care at the San Francisco Veterans Affairs Health Care System’s Opioid Treatment Program Clinic. Patients will learn about the risks of fentanyl and similar opioids, receive a fentanyl testing kit to screen any drugs being used, and be offered a kit for naloxone, which can reverse the effects of an opioid overdose.

MRP4-mediated PGE2 transport and tumor immunogenicity

Principal applicant: Deanna Kroetz, PhD, faculty member, Department of Bioengineering and Therapeutic Sciences

Award funding: $25,000

The project: Cancer immunotherapy harnesses a patient’s own immune system to eliminate tumors, but it doesn’t work for every patient. Some research has shown that cancer cells send molecular signals to each other, using “transporter” proteins to move signals outside of the cell, in a coordinated effort to resist the effects of immunotherapy. Kroetz will investigate the impact of a particular transporter, the multidrug resistance-associated protein 4 (MRP4), on the resistance of cancer cells to immunotherapy. She plans to characterize how MRP4 levels correlate with immunotherapy resistance and test the impact of MRP4 inhibitors on these drug-resistant cells.

Characterization of RAS proteins using chemical targeting and proteomics

Principal applicant: James A. Wilkins, professional research chemist, Department of Pharmaceutical Chemistry

Award funding: $7,500

The project: The RAS family of proteins is vital for normal cellular health, and mutations in these proteins are estimated to cause more than 30 percent of all cancers. Wilkins and his colleagues have developed a system that allows them to specifically isolate RAS proteins from cells or tissue samples for further testing. Wilkins will use this system to investigate the chemical modifications on RAS that spur tumor growth, aiming to better understand the behavior of the RAS protein both in healthy and cancerous cells.