FROM BENCH TO BEDSIDE: THE SCHOOL’S RESEARCH ENTERPRISE

FROM BENCH TO BEDSIDE

HOW THE SCHOOL'S DYNAMIC RESEARCH ENVIRONMENT FUELS DISCOVERY, CLINICAL APPLICATION AND INNOVATION

By Susan L. Wampler

While COVID-19 brought a dramatic reminder of the importance of biomedical innovation, pharmaceutical research has driven advances in healthcare throughout history. Creation of a smallpox vaccine in 1796, discovery of the world’s first antibiotic in 1929 and development in the 1990s of new classes of antiretroviral drugs to treat AIDS are just a few examples of research that has saved and extended millions of lives.

This drive to improve human health has remained at the heart of the USC School of Pharmacy’s mission since its founding in 1905. The school’s four departments— Clinical Pharmacy, Pharmacology and Pharmaceutical Sciences, Pharmaceutical and Health Economics, and Regulatory and Quality Sciences—provide a singular and dynamic environment for laboratory discovery, translational breakthroughs, clinical applications, policy solutions and regulatory innovation.

Here, we showcase just a few of the latest significant grants and research achievements of the school’s faculty.

FULL SPECTRUM “The school is unique in that we’re not just one discipline,” notes Annie Wong-Beringer, associate dean for research. “Our research extends from basic discovery to experimental therapeutics—and all the way to clinical trials and implementation and analysis of impact. We cover the entire spectrum of pharmaceutical discovery and health application.”

The School of Pharmacy’s research enterprise has been rewarded with significant grants from the National Institutes of Health (NIH), National Science Foundation (NSF), Department of Defense, and other government agencies and philanthropic foundations as well as contracts from the pharmaceutical industry that support the school’s collaborative approaches to

Stan Louie

Professor, Clinical Pharmacy

Recent grant

$1.6 million+ from the Department of Defense to promote nonfibrotic healing in an ocular globe injury model

What’s the main focus of your research?

I work on understanding how the body heals wounds. If we can understand that, perhaps we can prevent people from aging or getting conditions like Alzheimer’s or blindness. We’re working on developing drugs to promote regeneration.

What attracted you to this line of research?

I started out investigating viruses, such as those that cause HIV and cancer. What we found, interestingly enough, is that it’s not the virus but the inflammation caused by the virus that triggers cancer. My lab recently had a paper accepted in a highimpact journal that shows that if you stop inflammation, you can stop cancer.

What keeps you at USC?

It’s the people I work with at the School of Pharmacy and the USC Ginsburg Institute for Biomedical Therapeutics. I am on the team with Mark Humayun that created the world’s first artificial retina. I’m developing compounds to stop the cause of blindness, and we have three agents in either preclinical or late clinical trials or in human studies. One of the drugs, applied topically, can repair the eye without causing fibrosis—something no other drug has been shown to do.

drug development, targeting, delivery and discovery. Faculty members share their findings in top scientific journals and at major conferences. Their analysis informs new legislation and helps shape regulatory policy. A dozen faculty members hold patents, many of which have been licensed to industry.

INTERDISCIPLINARY PARTNERSHIPS “Our interdisciplinary environment fosters leading-edge research and strengthens the school’s dedication to revolutionizing healthcare through discoveries and innovations that enhance people’s lives,” says Papadopoulos, who with his team has successfully grown human testosteroneproducing cells in the lab, paving the way to someday treating low testosterone with personalized replacement cells.

In addition to the Keck School of Medicine, Los Angeles County + USC Medical Center, Keck Hospital and the Norris Comprehensive Cancer Center, alliances across USC include the Viterbi School of Engineering, Price School of Public Policy, Leonard Davis School of Gerontology, and Dornsife College of Letters, Arts and Sciences. However, School of Pharmacy research initiatives extend far beyond campus and California, with numerous external academic and industry partnerships across the nation and around the world. Frequent local collaborators include Caltech, Cedars-Sinai, City of Hope, Children’s Hospital Los Angeles, Kaiser Permanente School of Medicine and RAND Corp. LONGSTANDING CONTRIBUTIONS The school’s faculty members have long been recognized for their groundbreaking contributions—from University Professor Jean Chen Shih’s influential work illuminating how the brain enzyme monoamine oxidase (MAO) affects behavior to Enrique Cadenas’ study of the molecular mechanisms inherent in brain aging and Alzheimer’s disease. Shih is the Boyd and Elsie Welin Professor, and Cadenas holds the Charles Krown/ Alumni Professor of Pharmacology and Pharmaceutical Sciences.

Julio Camarero, the John A. Biles Professor in Pharmaceutical Sciences, won one of the first NIH “big idea” awards to “encourage projects so original that they have the potential to challenge fundamental beliefs.”

Houda Alachkar

Assistant Professor, Clinical Pharmacy

Recent grant

Five-year, $1.79 million grant from the NIH for a study that could lead to advancements in personalized treatments for acute myeloid leukemia.

How would you describe your research?

Basically, I do translational and functional genomics. The big goal is to identify therapeutic targets from samples from public data and translate those advances to patient care.

What is the big problem you’re trying to solve?

Currently, the overall survival rate for patients with acute myeloid leukemia is less than 30%. This outcome is significantly worse for older patients. There’s a high need to identify new therapeutic targets to improve outcomes for all patients with this disease.

Why is USC a great place to do your work?

Being in the School of Pharmacy allows me to collaborate with biochemists, pharmaceutical scientists and bioengineers, which helps us formulate targets into therapeutic approaches and strategies. We’re also in close proximity to the USC Norris Comprehensive Cancer Center, which helps us validate our findings with patient cohorts and bring ideas from patients to study in the lab. The interaction with clinicians, hematologists and oncologists is absolutely vital. RESEARCH CENTERS

The School of Pharmacy’s mission of innovation includes major research centers, institutes and partnerships that drive discovery, improve access to quality, cost-effective healthcare, and lead the convergence of science, healthcare and policy:

USC Institute for Addiction Science

Center for Drug Discovery and Development

USC Ginsburg Institute for Biomedical Therapeutics

D. K. Kim International Center for Regulatory Science

Center for Quantitative Drug and Disease Modeling

Leonard D. Schaeffer Center for Health Policy & Economics

Southern California Clinical and Translational Science Institute

Titus Center for Medication Safety and Population Health

Center for USC-Taiwan Translational Research

Annie Wong-Beringer

Associate Dean, Research Professor, Clinical Pharmacy

What are the major problems you’re trying to solve?

Staph aureus is a skin bacterium that we all have, and it’s a leading cause of bloodstream infection. One out of three people with the best treatment currently available will continue to grow the bacteria in the blood, which is problematic because it not only gets seeded into other organs but such patients also will have a much higher likelihood of death. By better understanding the host and pathogen interaction, we can improve how we direct treatment.

Geoffrey Joyce

Chair and Associate Professor, Department of Pharmaceutical and Health Economics

What are the key problems you’re trying to solve?

I focus on applying economics to the pharmaceutical industry, the decisions people make about consuming prescription drugs and the impact of drugs on their health. Drugs are very expensive and they should be priced based on their value instead of demand or what a firm can charge. So I am working on how to bring value to the healthcare space, particularly in pharmaceutical pricing.

Zhipeng Lu

Assistant Professor, Pharmacology and Pharmaceutical Sciences

Recent grant

Five-year, $2 million+ R35 grant from the National Institute of General Medical Sciences to develop new chemical and computational tools to study RNA structures

What’s the main focus of your research?

My lab focuses on RNA machines in living cells. We develop and apply novel technologies to understand the structures and functions of RNA molecules in basic cellular processes, with the ultimate goal of treating human diseases, including genetic disorders, cancers and viral infections.

Why is this work important?

RNA viruses include coronaviruses, Zika, HIV, Ebola and many others that cause terrible diseases. We’re studying their structures and interactions with the host, and we hope to unravel a totally different direction for drug discovery.

Why did you choose USC?

USC is a really nice place to do research, and we already have lots of collaborations. The school is very supportive of our work, and we have colleagues to help with research, grant writing and publication. He recently earned a new patent for a novel cyclotide for potential use in treating cancer and heart attack.

Meanwhile, Clay Wang, chair of the Department of Pharmacology and Pharmaceutical Sciences, and collaborators at Jet Propulsion Laboratory garnered a grant from NASA to launch a pioneering study of fungi in outer space.

Under the leadership of founding director Dana Goldman, the Schaeffer Center for Health Policy & Economics has received more than $64.5 million in government funding since its inception in 2009. More than $6 million of that amount is from NIH funding through the prestigious Resource Centers for Minority Aging Research (RCMAR) program. USC-RCMAR supports pilot projects by junior scholars focused on addressing disparities in the health and economic wellbeing of minority elderly populations with Alzheimer’s disease.

RAPIDLY GROWING PORTFOLIO In just the past two years, the school has secured numerous major grants as well.

With $3.6 million in support from Arnold Ventures, Erin Trish, co-director of the Schaeffer Center, serves as principal investigator on a portfolio of research and policy projects to improve understanding of rising healthcare spending by taking a data-driven look at provider prices, market consolidation, private equity, consumer costs, and the patchwork of state and federal laws that attempt to offer solutions.

Hygeia Centennial Chair Dima Qato’s recent study revealing that pharmacy deserts disproportionately affect Black and Latino

Carla Blieden and Richard Dang

Assistant Professors, Clinical Pharmacy

What have you learned from the COVID-19 vaccination clinics?

Through our COVID-19 vaccination efforts, we’ve become even more familiar with areas in Los Angeles that would benefit from the types of health services that the school has long provided. We will take these best practices and target our wellness events at the locations that need us most. We’ve also been able to demonstrate the value of having a pharmacist on the team to the point where our partners request a pharmacist at every vaccination site. We presented a poster, “School of Pharmacy Led Interdisciplinary Mass COVID-19 Vaccination Program for a Large Urban City,” on these efforts at the American Association of Colleges of Pharmacy’s annual meeting.

Paul Beringer

Chair and Professor, Titus Family Department of Clinical Pharmacy

What is the main focus of your research?

I started working on cystic fibrosis research in 1996, when the life expectancy for someone with the disease was 28 years. Now it’s pushing 50 years of age. In 2019, a new therapy was introduced that corrects the gene defect, resulting in significant improvement in lung function. But because the drug gets broken down by the liver, the therapy is contraindicated for some patients. My lab received funding from the Cystic Fibrosis Foundation for a clinical trial to validate an alternative drug.

William Padula

Assistant Professor, Pharmaceutical and Health Economics

Tell us about your research.

I focus on comparing the value of different treatments as well as on modeling the use of pharmaceuticals and new surgical techniques to evaluate the most effective treatments for patients so they get the best-quality care for the best value.

residents was funded by the National Institute on Aging and the Robert Wood Johnson Foundation.

Serghei Mangul was awarded a $750,000 grant from the NSF in March to develop scalable bioinformatics methods to study the immune response, and another NSF grant of $199,000 in July. He aims to create robust, data-driven, computational approaches to improve human health.

Paul Beringer, chair of the Titus Family Department of Clinical Pharmacy and an expert in cystic fibrosis, earned a $335,000 grant from the Cystic Fibrosis Foundation in April.

Last year, Jianming Xie received a two-year, $460,000 R21 grant from the National Institute of Allergy and Infectious Diseases for an HIV study. He also was recently awarded two grants from the Ming Hsieh Institute and a Technology Advancement Grant for his work in developing treatments for acute myeloid leukemia.

Bangyan Stiles and collaborators at the USC Viterbi School of Engineering garnered a $636,000 NIH grant to develop statistical methods that aggregate small datasets to extend their value.

Many of the school’s faculty members added COVID-19 investigations to their portfolio over the past two years. Beringer and colleagues are developing a peptide treatment for COVID-19 pneumonia. William Padula is examining the importance of testing for COVID-19 to understand asymptomatic infection as well as the association between national concentrations of registered nurses and mortality from the disease. Wong-Beringer, Houda Alachkar, Mangul, Emi Minejima and collaborators are exploring T cell repertoire changes in infected subjects. Wong-Beringer and Minejima are also studying secondary bacterial infections in patients hospitalized for COVID-19. Stan Louie is evaluating the anti-hypertension drug telmisartan for treating COVID-19.

“The school’s research enterprise continues to evolve and grow,” Papadopoulos says. “Our commitment to improve lives remains constant.”

Yong (Tiger) Zhang

Assistant Professor, Pharmacology and Pharmaceutical Sciences

Recent grants

Four-year, $2 million+ R01 NIH grant to reprogram exosomes for biomedical applications; five-year, $1.9 million NIH General Medical Sciences grant to advance understanding of complex ADP-ribosylation processes

What’s the main challenge addressed by your current research?

Scientists used to think that exosomes— small vesicles secreted by cells—were just dumpsters of excreted waste. In the last 10 years, though, we’ve realized that these extracellular vesicles mediate communications between cells and organs throughout the body. This is the mechanism through which cancer and other diseases metastasize to invade tissues and organs. But if diseases can be communicated in this way, why can’t we also use exosomes to reach affected areas with curative therapies?

How are you designing these new therapies?

Exosomes can recognize immune cells as well as tumor cells. We are using this knowledge to generate innovative, exosome-based therapeutics to both target and treat cancer. Since vesicles can carry certain nucleic acid-based therapeutics, the technology could also potentially be used for neurodegenerative diseases.

What makes USC a good setting for your work?

At USC, I can recruit the most talented postdocs and graduate students. Without their hard work, we cannot be successful. Here we also have access to world-class facilities and great collaborators—including clinical physicians and immunologists from the Keck School of Medicine, who can help study the therapeutic effectiveness of the exosomes we generate.

Eunjoo Pacifici

Chair and Associate Professor, Department of Regulatory and Quality Sciences

What is the focus of your work?

In addition to our top-flight educational initiatives, the Department of Regulatory and Quality Sciences maintains a hub for research groups that develop new products for unmet medical needs. We have an affiliation with the Southern California Clinical and Translational Sciences Institute, which focuses on improving health outcomes for diverse communities. Our Regulatory Science Consulting Center enables students to build expertise by working alongside faculty and other specialists in helping innovators navigate regulatory matters.