2021 Mary Anne Koda-Kimble Seed Award for Innovation funds tomorrow’s discoveries

The UCSF School of Pharmacy's 2021 Mary Anne Koda-Kimble Seed Awards for Innovation, given in honor of the School’s former dean, were awarded to eight projects across education, clinical research, and basic science.

Applicants were encouraged to submit their boldest, riskiest, and most blue-sky ideas—those for which there are no ready or traditional sources of funding.

The awards will help fund research on cancer, neurodegeneration, evaluations of the School’s new health equity curriculum, and interventions into depression and anxiety cases, among other projects.

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

High-throughput integration of single-cell morphology and transcriptome for metastasis prediction

Principal applicant: Kai-Chun Chang, PhD, postdoctoral scholar, Department of Bioengineering and Therapeutic Sciences

The project: Despite sharing the same genetic code, cells take on a variety of shapes and structures in the human body. Chang believes that studying the cell morphology (CM) of cancer cells could shed light on how cancer cases progress and could improve predictive power for drug responses and targeted therapies. Chang wants to use a technology called printed droplet microfluidics (PDM) platform with barcoded nanowells to collect CM data on a set of highly variable cancer cells.

Evaluation of a health equity curriculum

Principal applicant: Stephanie Hsia, PharmD, faculty member, Department of Clinical Pharmacy

The project: In response to the health inequities revealed by the COVID-19 pandemic, the School adopted a new health equity curriculum in the fall 2020. This class teaches students to identify and recognize structural causes of health disparities, design interventions to reduce structural causes of health disparities, and to engage in equitable, civil, and compassionate discussions about systemic racism and implicit biases. Hsia plans to use surveys and conduct an analysis with independent researchers to see how well the new curriculum worked, with the goal of expanding it to other pharmacy schools.

Discovering powerful biocatalysts with microscale mass spectrometry

Principal applicant: Linfeng Xu, PhD, postdoctoral scholar, Department of Bioengineering and Therapeutic Sciences

The project: Enzymes are tiny molecular machines that complete chemical tasks quickly and accurately. They can be used to create everything from medicines to biofuels, but engineering useful enzymes is a slow and error-prone process. Xu hopes to speed up the process of discovering enzymes using microscale mass spectrometry, which could help identify new useful enzymes for science and industry.

PCM1 function in the asymmetric radial glial progenitor division

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

The project: Xiang wants to investigate the role of a protein named pericentriolar material 1 (PCM1) in severe neurodevelopmental disorders. Xiang plans on disabling or removing genes related to PCM1 in an animal model and compare the results to models with the genes still working. The results could improve our understanding of brain disorders and neural degeneration diseases, such as schizophrenia and Huntington’s disease.

A unique approach to inducing protein degradation for undruggable targets

Principal applicant: Markella Konstantinidou, PhD, postdoctoral scholar, Department of Pharmaceutical Chemistry

The project: Protein–protein interactions (PPIs) play a crucial role in important biological processes and are often dysregulated in disease, making them an attractive target for new therapies. An emerging strategy for controlling PPIs, called proteolysis–targeting chimeras (PROTACs), allows scientists to engineer molecular linkers that draw the “trash collectors” of the cell to certain proteins, destining those proteins for destruction. Konstantinidou intends to design PROTACs for protein targets known as intrinsically disordered proteins (IDPs), which currently can’t be targeted by drugs. Her team will engineer a PROTAC using an adaptor protein that binds to the estrogen receptor, an IDP which is expressed on many breast cancer cells, leading to the estrogen receptor’s degradation. If successful, the work could be applied to a variety of IDPs that are associated with disease.

Using neuronal activity profiling and transcriptomics to resolve drug/target engagement in vertebrates.

Principal applicant: Matthew McCarroll, PhD, postdoctoral scholar, the Department of Pharmaceutical Chemistry

The project: A variety of drugs, ranging from benzodiazepines to Ambien, work by interacting with proteins, known as GABA receptors, found on the outside of neurons. However, it is unclear why these drugs have divergent effects on the brain and behavior. Due to variation in the sub-components, or “sub-units,” of these proteins, there may be many different types of GABA receptors, some of which are more responsive to certain drugs than others. McCarroll plans to use a new biochemical tool, called CaMPARI, to monitor how different drugs affect individual neurons in zebrafish, which possess many of the same varieties of GABA receptors as humans. CaMPARI undergoes a change in its fluorescent color only under ultraviolet light when a neuron is activated, providing a read-out of which neurons are sensitive to each drug. McCarroll will use this feature of the tool to not only identify the shapes and locations of active neurons, but to also isolate their RNA, cell by cell, to determine which types of GABA receptor are responsible for each drug’s effects.

Endogenous role of solute carrier 22 family member, SLC22A15

Principal applicant: Sook Wah Yee, PhD, postdoctoral scholar, Department of Bioengineering and Therapeutic Sciences

The project: SLC22A15 is one of many cellular “transporters," which are a class of proteins responsible for moving ions and small molecules across the cell membrane. The SLC22A15 transports antioxidants through the cell membrane, and that may suggest it plays a role in metabolic diseases, such as obesity and diabetes. Yee proposes using an animal model to test SLC22A15’s role in lipid and glucose metabolism.

A pharmacist-led closed loop artificial intelligence (AI) mental health platform

To decrease hospitalizations and treatment failure in patients with major depressive disorder (MDD) and generalized anxiety disorder (GAD) in light of the COVID-19 pandemic

Principal applicant: Harini Bhat, PharmD student, class of 2021

The project: The COVID-19 pandemic significantly increased the number of cases of major depressive disorder (MDD) and generalized anxiety disorder (GAD). Unfortunately, both MDD and GAD patients are likely to skip medication doses or stop taking them altogether. Bhat wants to use Totum Health, an artificial intelligence (AI) mental health platform, to find possible risk factors for hospitalization in 200 deidentified patients currently on an antidepressant or anti-anxiety medication. The AI platform can flag MDD and GAD patients at risk for hospitalization so a pharmacist can counsel them on their drugs. Bhat thinks the intervention could cut hospitalizations in those cases by 30 percent.