Mangul Awarded $3 9M NIH Grant

Serghei Mangul combines expertise in computational biology and bioscience to help close the digital divide that can prevent life scientists from maximizing the potential of data-driven investigation. He recently was awarded a five-year, $3.9 million National Institutes of Health (NIH) grant to fuel this work further.

“This funding will support my lab’s efforts to create open-source software tools and easy-to-use databases to study adaptive immune repertoires across diverse populations,” says Mangul, an assistant professor of clinical pharmacy at the Mann School.

He notes that limiting immunogenomics studies to people of European ancestry restricts the ability to identify variations in human adaptive immune responses. Thus, expanding the diversity of those studied is vital to advancing the frontiers of human immunology.

“Current databases are ill-equipped to serve non-European populations and thus we should move the research to diverse populations,” he adds. “Without doing that, we cannot serve underrepresented racial and ethnic groups.”

NIH Mentoring Fellowship

Mangul, who joined the USC Mann faculty in 2019, focuses on improving the techniques of bioinformatics—computational analysis of biological data—to better understand the mechanisms of disease.

In October 2022, he was selected to participate in the inaugural NIH cohort of the Artificial Intelligence/Machine Learning Consortium to Advance Health Equity and

Researcher Diversity Fellowship Program in Leadership.

As part of the nine-month program, Mangul is mentoring Chitra Nayak, associate professor at Tuskegee University, in developing a machine-learning algorithm to determine the role of ancestryassociated mutations in reprogramming the transcriptional profile linked to aggressive cancer and high mortality among African Americans.

Mangul hopes this training in the use of artificial intelligence/machine-learning methods will result in future programs at Tuskegee University to empower students with cutting-edge methods for analyzing and interpreting large-scale, next-generation sequencing datasets across diverse populations.

Reforming The Dialysis Market

Fifteen percent of the U.S. population has chronic kidney disease. At its most severe, end-stage kidney disease (ESKD) requires patients to receive dialysis regularly or have a kidney transplant. According to the Centers for Disease Control and Prevention, some 750,000 Americans have ESKD, with more than 70% of that number needing regular dialysis treatment. Although dialysis is lifesaving in the short term, five-year mortality rates still exceed 60%.

Most patients with ESKD receive health insurance through Medicare, which provides coverage for patients with kidney failure regardless of age. However, a growing number are covered through private payers. In research published in JAMA Internal Medicine, Schaeffer Center Co-Director Erin Trish and colleagues found that monthly spending on ESKD-related outpatient dialysis services was three times higher in the individual market than through Medicare. This raises concerns that dialysis centers are steering patients into the individual market—and costing the healthcare system more in the process.

“Our study shows that, even though the number of dialysis patients in the individual market is relatively small, because their spending is so high, this enrollment can actually raise premiums across the entire individual market,” Trish says.

Congresswoman Katie Porter (D-Calif.) cited the team’s research in a report calling for robust oversight of the dialysis industry.

Since two large companies dominate that industry, Trish notes that any effective oversight must grapple with the dialysis market’s heavy consolidation. This need became even greater when the 21st Century Cures Act allowed patients with kidney failure to enroll in Medicare Advantage, the private-sector alternative to traditional Medicare. Medicare Advantage plans pay 27% more than Medicare for the median price of outpatient dialysis treatment, Trish’s research shows. Without significant reforms to increase competition, such high markups will ultimately increase premiums and reduce benefits.

New Faces

Dean Appointed Honorary Investigator

Mann School Dean Vassilios Papadopoulos has been named an honorary investigator by the Research Institute of the McGill University Health Centre (RI-MUHC). The appointment recognizes his distinguished contributions in multiple roles at RI-MUHC, where he served as executive director, chief scientific officer and faculty member before joining USC in 2016. While at McGill, Papadopoulos was also a senior scientist in its Metabolic Disorders and Complications Program, holder of the Phil Gold Chair in Medicine, and a mentor to numerous researchers and trainees.

The honorary investigator appointment was created in 2019 to recognize researchers for exceptional contributions to RI-MUHC, their field or both. “Vassilios Papadopoulos’ achievements serve as an example and inspiration for the current RI-MUHC research community,” the institute’s leaders noted in a statement.

Allison Chacon, PharmD ’20, has joined the USC Mann School as assistant professor of clinical pharmacy (clinician-educator) in the Titus Family Department of Clinical Pharmacy. Her focus includes community and ambulatory care, helping support the new South Los Angeles Pharmacy, maintaining a clinical service with the Department of Rheumatology at Keck Medicine of USC and teaching the Mann School’s nonprescription therapies course. Chacon had been practicing as a clinical pharmacist at the USC Medical Plaza Pharmacy since completing two years of postgraduate clinical residency training at USC Mann.

Brian Ma, PharmD, has been appointed an assistant professor of clinical pharmacy (clinician-educator) in the Titus Family Department of Clinical Pharmacy and co-director of Introductory Pharmacy Practice Experience Programs at the Mann School. He is a board-certified pharmacotherapy specialist as well as interim director of interprofessional education for the school. His current practice site is in the inpatient internal medicine setting at the Los Angeles County+USC Medical Center, where he provides clinical pharmacy services for hospitalized patients. He earned his PharmD at the University of California, San Francisco.

Saving Money but Increasing Risk

Although warfarin is the standard treatment for lowering the risk of stroke from atrial fibrillation, non–vitamin K antagonist oral anticoagulants (NOACs) have emerged as a more effective alternative with fewer side effects. NOACs also tend to be more expensive. Research led by Geoffrey Joyce and Seth Seabury finds that the formulary restrictions used by insurers and pharmacy benefit managers to save money result in fewer patients using NOACs or warfarin— which likely leads to poor health outcomes.

The study finds that beneficiaries in Medicare Part D plans with restricted access to NOACs have a lower probability of using the drugs, and those with reduced access show worse medication adherence. In addition, patients in the sample faced longer delays in filling their initial prescription after an atrial fibrillation diagnosis. This all adds up to a higher aggregate risk of death, stroke, transient ischemic attacks or systemic embolism for patients with restricted coverage.

The researchers note that, while formulary restrictions can be appropriate, such policies should be continuously reviewed to ensure that patients have timely access to effective medications.

Camarero Receives Lung Cancer Research Grant

The American Lung Association has awarded Julio Camarero a $200,000 Lung Cancer Discovery Research Grant for the project “Therapeutic Targeting of Hdm2/HdmX E3 Ligase in Lung Carcinoma.” His lab has discovered a novel cyclotide and is working on different strategies to improve the cellular uptake and pharmacokinetic profiles of bioactive cyclotides. Camarero is the John A. Biles Professor in Pharmaceutical Sciences.

Faculty Books

Terry David Church—Doctor of Regulatory Science ’17, MS Regulatory Science ’15, assistant director of undergraduate programs, and assistant professor in the Department of Regulatory and Quality Sciences— recently published his first textbook, Hidden History: Drugs, Geography, and Human Addiction

William Padula—a Schaeffer Center fellow and assistant professor in the Mann School’s Department of Pharmaceutical and Health Economics—is co-author of a new book, Handbook of Applied Health Economics in Vaccines, published by Oxford University Press.

ELUCIDATING COVID’S IMPACT

Associate Dean for Research Affairs Annie Wong-Beringer and colleagues conducted a detailed analysis of nonelderly adults hospitalized with COVID-19 between March and November 2021 to identify age-differentiated characteristics and outcomes between two waves of the pandemic: the original Alpha form and the more severe Delta variant. Unvaccinated individuals required prolonged hospital stays with more than half remaining on oxygen at the time of hospital discharge.

Risk for severe disease and worse outcomes increased substantially with every 10-year increment between ages 25 and 64. The study demonstrated that such risk had been underappreciated in unvaccinated nonelderly adults, especially the middle-aged cohort, despite their being younger and having fewer comorbid conditions.

QATO GARNERS $1.65M GRANT

Computer illustration of a lipid nanoparticle mRNA vaccine, a type of vaccine used against COVID-19 and influenza.

Published in the Journal of Primary Care Community Health, the study emphasized the importance of prioritizing vaccination efforts for this population, particularly in light of the impact on children and families. Some 65% of children facing orphanhood as a result of COVID-19 belong to families of racial and ethnic minorities. The study also noted the toll on household income and food security in families of adult caregivers with lingering health issues from long COVID.

Dima M. Qato has been awarded a four-year, $1,650,000 grant from the National Institute on Aging to address structural racism and advance policies within Medicare Part D to prevent pharmacy closures and advance equitable access to medicines.

Despite evidence that pharmacy closures contribute to declines in medication adherence, rigorous investigations on the extent and impact of structural racism within Medicare Part D—policies that reinforce differential access to resources and opportunities— have not been conducted, according to Qato.

“We need to shift the focus within Medicare Part D payment and delivery reform from addressing individual-level barriers toward addressing structural racism and how it operates at the community level, specifically pharmacy closures, to adversely affect minority older adults living in segregated neighborhoods,” says Qato, Hygeia Centennial Chair at the USC Mann School and a senior fellow at the USC Schaeffer Center for Health Policy & Economics. “The failure to do so may undermine ongoing efforts to reduce disparities.”

A public health advocate and community pharmacist, Qato aims to generate new evidence to guide Medicare Part D payment and delivery reforms to protect pharmacies from closure. For older adults who rely on their local pharmacies, Qato’s project aims to reduce disparities in medication access and advance health equity.

“Pharmacy closures may be an overlooked communitylevel mechanism of structural racism that exacerbates the adverse consequences of segregation on disparities in pharmacy access and medication adherence,” says Qato, director of the Program on Medicines and Public Health. She also holds a joint appointment with the USC Spatial Sciences Institute at the USC Dornsife College of Letters, Arts and Sciences.

“The goal of this project is to evaluate the extent and impact of pharmacy closures on medication adherence among chronically ill older adults with Medicare Part D and identify subgroups most at risk for nonadherence post-closure.”