Researcher uses mammal DNA to zoom into human genome with unprecedented resolution

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USC researcher uses mammal DNA to zoom into the human genome with unprecedented resolution

Steven Gazal has identified base pairs of DNA that play a crucial role in human disease.
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“Why do humans have disease if they went through millions of years of evolution?” It’s a question Steven Gazal, PhD, assistant professor of population and public health sciences at the Keck School of Medicine of USC, hopes to answer.

Gazal is part of an international team of researchers who have become the first to precisely identify base pairs of the human genome that remained consistent over millions of years of mammalian evolution, and which play a crucial role in human disease. The findings were published in a special Zoonomia edition of Science.

Gazal and his team analyzed the genomes of 240 mammals, including humans, zooming in with unprecedented resolution to compare DNA. They were able to identify base pairs that were “constrained” – meaning they remained generally consistent – across mammal species over the course of evolution. Individuals born with mutations on these genes may not have been as successful within their species or were otherwise not likely to pass down the genetic variation. “We were able to identify where gene mutations are not tolerated in evolution, and we demonstrated that these mutations are significant when it comes to disease,” explains Gazal.

The team found that 3.3% of bases in the human genome are “significantly constrained,” including 57.6% of the coding bases that determine amino acid position, meaning these bases had unusually few variants across species in the dataset. The most constrained base pairs in mammals were over seven times more likely to be causal for human disease and complex trait, and over 11 times more likely when researchers looked at the most constrained base pairs in primates alone.

The dataset was provided by the Zoonomia consortium, which according to the project website, “is applying advances in DNA sequencing technologies to understand how genomes generate the tremendous wealth of animal diversity.” Gazal gives credit to Zoonomia for making this type of data available to researchers and anticipates it will be widely used by human geneticists. “It’s a cheap resource to generate, as opposed to datasets generated in human genetic studies,” says Gazal.

His team’s findings are a significant step forward, as Gazal notes, “we do not understand 99% of the human genome, so it is fundamental to understand which part has been constrained by evolution and is likely to have an impact on human phenotypes.” Their discoveries and methods could become crucial tools for further research.

The next step for Gazal and his team is to repeat the process with a primate-only dataset. By restricting the subjects, they hope to focus on functions of DNA that appeared more recently in human evolution. “We expect this to be even more useful in determining information on human disease,” says Gazal.


For more information and a complete list of authors, access the paper here.

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USC Schaeffer Center research director testifies at congressional hearing


Schaeffer Research Director Testifies at Congressional Hearing on Biomedical Innovation and Patient Access

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USC Schaeffer Center research director testifies at Congressional hearing


Darius Lakdawalla testifies before the U.S. House Ways and Means Subcommittee on Health, discussing biomedical innovation and patient access.

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In a hearing on how to balance incentives for medical innovation with patient access, USC Schaeffer Center Director of Research Darius Lakdawalla shared findings demonstrating that “expanding prescription drug coverage is worth the cost because it simultaneously rewards innovators and makes innovation more accessible.”

In testimony before the U.S. House Ways and Means Subcommittee on Health on May 10, Lakdawalla suggested targeted reforms to the Inflation Reduction Act (IRA) of 2022 as well as Centers for Medicare and Medicaid Services (CMS) programs that would improve the system for patients and innovators. Lakdawalla is noted for his studies on how to cost-effectively stimulate biomedical innovation so that as many patients as possible can benefit from its breakthroughs.

He was part of a panel of experts called upon by the subcommittee for a hearing on “Examining Policies that Inhibit Innovation and Patient Access.” The subcommittee, chaired by Rep. Vern Buchanan (R-Fla.), addresses matters related to payment programs for healthcare, medical delivery systems and related research.

“We all want America to lead the world in medical innovation, and we want Americans to have access to the newest, best groundbreaking treatments as soon as possible,” Rep. Buchanan said. “I hope we can leave this hearing today with a renewed sense of bipartisanship and willingness to work together on policies that protect and enhance innovation.”

Balancing innovation costs with meeting patient needs
“The tradeoff between incentives for innovation and healthcare access for patients is typically framed as an either/or proposition,” Lakdawalla explained. “Either we reward innovators with high prices and deny many patients access to therapies they desperately need, or we make new therapies broadly accessible by limiting their prices, starving innovators of rewards for developing new drugs.”

He then noted how Schaeffer Center research presents potential solutions to this dilemma. “Generous prescription drug coverage can serve as the knife that cuts through this knotty tradeoff,” he said.

“Better lives for patients and their families is the goal,” Lakdawalla emphasized. So instead of paying for all innovations, he said the focus should be on rewarding those companies that “seek out and develop new medicines that help us achieve healthier outcomes.”

Aligning price with value
Such an approach requires measuring the value of new medicines, but Lakdawalla observed that traditional economic analyses, such as quality-adjusted life-years (QALYs), are inaccurate. Instead, he said that Schaeffer Center research has revealed the advantages of value assessment models adhering to the “principle that goods are more valuable to people who have less of them. Analogously, health improvements are more valuable for people with disabilities, terminal illness or other severe disease.”

Such a strategy, he added, “also comports with federal law by avoiding value assessments that discriminate against vulnerable patients with disabilities or terminal illness.”

Yet while the IRA “provides an opportunity to better align price and value for individual drugs,” Lakdawalla said the law needs revision to incorporate “credible, evidence-based and scientifically validated methods for measuring value to patients.”

In response to concerns raised by Kevin Hern (R-Okla.) about the IRA’s policy changes related to rare-disease therapies, Lakdawalla noted that the likely result will be reduced innovation in this category. Therefore, he said, reforms should address the unmet needs of people with rare diseases because, in such cases, “even a relatively modest improvement in health can be quite valuable. And that needs to be accounted for in the way CMS sets maximum fair prices to at least mitigate some of these issues for rare disease where value is at a premium.”

Three-part pricing

To better align a drug’s cost with its value, Schaeffer Center investigators suggest a three-part-pricing model that starts with an evaluation phase. During this initial period, Lakdawalla explained, the drug would be introduced at “a lower price in exchange for early access to Medicare coverage and the possibility of exemption from IRA inflation rebates if the drug meets prespecified effectiveness benchmarks.”

This would be followed by a reward phase. “If the drug achieves its targets, innovators would be rewarded with a high price,” he said. Otherwise, they would not.

In the final phase, robust generic or biosimilar competition would drive down prices upon the drug’s loss of exclusivity, improving patient access in the long term.

“While there is value in reducing healthcare costs and improving patients’ access to existing drugs in the short term, there is also value in ensuring a continuing stream of innovative therapies for future generations,” Lakdawalla noted. Achieving both aims, however, requires a balanced–and bipartisan approach. The results, however, will be worth the effort, he said.

“By ensuring generous prescription drug insurance, drug prices that reflect the value they deliver and effective competition throughout the pharmaceutical supply chain, we can achieve improved health for Americans today and tomorrow,” Lakdawalla said. “Getting prices right would go a long way toward addressing the different symptoms of our various economic diseases in this market.”

The hearing was webcast live and may be viewed on YouTube. Other panelists were Ted Okon, executive director of the Community Oncology Alliance; Joshua Makower, director of the Stanford Byers Center for Biodesign at Stanford University; Aaron S. Kesselheim, professor of medicine at Harvard Medical School; and Tony Gonzales, national early-stage advisor for the Alzheimer’s Association–who spoke about his battles accessing care after his own Alzheimer’s diagnosis before age 50.

Read Lakdawalla’s testimony in full.

Lakdawalla also serves as Quintiles Chair in Pharmaceutical Development and Regulatory Innovation at the USC Mann School of Pharmacy and Pharmaceutical Sciences and is a professor at the Price School of Public Policy. The Schaeffer Center is a partnership of the Mann School and Price School.

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How vaccine hesitant are you? A third of Americans aren’t fully protected against COVID

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Are You More Vaccine Hesitant Than A 57-Year-Old?
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In May 2021, U.S. President Joe Biden announced his goal as getting at least 70% of Americans partially vaccinated against COVID-19 by July of that year. However, government records indicate that as late as September 2022, more than 31% of Americans were still not fully vaccinated. It has been shown this was not due to supply constraints, but rather, due to vaccine hesitancy among certain segments of the population.

Why were so many Americans hesitant about the COVID vaccine?

This is what researchers at USC Viterbi School of Engineering set out to answer. Mayank Kejriwal, Research Lead at the USC Information Sciences Institute (ISI) and a Research Assistant Professor in the Daniel J. Epstein Department of Industrial and Systems Engineering, along with PhD student Ke Shen analyzed socio-demographic variables in their paper, Using Conditional Inference To Quantify Interaction Effects of Socio-Demographic Covariates of Us COVID-19 Vaccine Hesitancy, which was recently published in PLOS Global Public Health.

With this research, they hope to lay the groundwork for future pandemic preparedness with regard to vaccine hesitancy.

Survey Says…
Kejriwal conducted a retrospective analysis on data from a COVID-19 cross-sectional Gallup survey that was administered to a representative sample of U.S.-based respondents. It was an online survey that began in March 2020, and included daily random samples of U.S. adults.

“We wanted to see whether we could predict, based on socio-demographic variables, what specific groups might be more vaccine hesitant than others,” said Kejriwal. He explained, “If we can predict that, then you could target the communication. You might know that these are the communities where we need more vaccine awareness, for example.

Using the responses of 16,322 respondents, he analyzed the relative effects of different categories of demographic variables on vaccine hesitancy. These variables were: annual household income, race/ethnicity, political party, employment status, gender, education, and “trust in the Trump administration.”

For this final variable, the 2020 Gallup question asked: ‘Please think about the recent impact of the coronavirus (COVID-19) on your life when responding to the following and indicate your level of agreement or disagreement: I have confidence in the leadership of President Donald Trump to successfully manage emerging health challenges.’ Responses to this question were recorded on a five-point scale, from strongly disagree (1) to strongly agree (5). Those who responded greater than 3 were identified as individuals who had trust in the Trump administration

How (and By How Much) Do These Variables Affect Vaccine Acceptance?
Kejriwal had two goals in mind for the survey data: 1) find the associations between the variables and vaccine acceptance; and 2) quantify and visualize the interactions between those variables and vaccine acceptance.

Using univariate regression – a model that looks to find the relationship between one variable and a target variable (vaccine acceptance in this case) – Kejriwal analyzed the Gallup data to find and measure the associations

Additionally, Kejriwal used machine learning and deep statistical analysis to take the variables and the associations between them and vaccine hesitancy and organize them into a conditional inference tree. This tree is a way to quantify and visualize the relative importance of the variables, and also show the effects between the variables

The tree shows, for example, a male non-Black Democrat who did not trust the Trump administration had high vaccine acceptance. Whereas a female under age 57 who trusted the Trump administration had very low vaccine acceptance. Both of these might seem intuitive, but with the conditional inference tree, the degree of vaccine acceptance and the relationship between the variables is quantified and visualized.

And the thought is that, with this level of precision, communications strategies could be more targeted and effective. Kejriwal found clear patterns between vaccine acceptance among different socio-demographic groups in the U.S. and hopes that his methods can be used to predict vaccine hesitancy if we ever face another pandemic.

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New USC Mann and Naval ROTC grad will soon commission in the U.S. Navy


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Commencement Spotlight: Jack Saville

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New USC Mann and Naval ROTC grad will soon commission in the U.S. Navy
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By David Zong

Since kindergarten, Jack Saville has dreamed of being in the U.S. Navy. He joined the Naval Reserve Officers Training Corps (NROTC) program three weeks after arriving at USC. And on May 12, he will graduate with a degree in pharmacology and drug development from USC Mann School of Pharmacy and Pharmaceutical Sciences.

Saville said he always had the urge to serve the country. He grew up in Manhasset, N.Y., in a family where many others have also joined the military. Saville’s great-uncle served in a tank battalion during the Battle of the Bulge in World War II.

At USC, Saville and his fellow cadets meet three to four times a week for training while “integrating themselves into the military lifestyle.” The ROTC lifestyle is atypical for Trojans: waking up as early as 5 a.m., completing intensive physical and leadership training, and wearing the uniform around campus. “It definitely makes you stick out in a crowd,” Saville said. “It’s a reminder of the commitment that you have made to serve our country.”

Through the Naval ROTC program, Saville received a three-year scholarship that paid for his education at USC. He signed on for a five-year commitment to the U.S. Navy after graduation.

“Being a part of the Naval ROTC Battalion at USC has been a gratifying experience,” Saville said, noting that the program provided him with naval knowledge, leadership skills, and friendships for life. Saville added that he uses the Navy’s core values of honor, courage and commitment when evaluating problems or trying to make ethical decisions. And by doing so, he has the ability to look at issues from different perspectives, setting him apart from peers in other classes.

When he first came to USC in January 2020, Saville was lost and overwhelmed just like other first-year students. He said that once he found his place at USC Mann and in the ROTC program, “everything fell into place.”

Saville originally came to USC as a biochemistry major. Later, his curiosity and passion for science took him to the world of pharmacology and drug development–fields he instantly fell in love with after taking the History and Geography of Drugs class with Terry David Church, assistant professor of regulatory and quality sciences.

“One of the best feelings in the world is walking into class, and not only being close with classmates but also with your professor,” Saville said. “That was an important part of my life here at USC, and it played a huge role in my happiness as a student at USC Mann.”

His coursework included a few unforgettable classes, including “Ethics, Drugs and Society” and “Mysterious Deaths: From Poisons in Literature and History to Forensic Toxicology.” Another memorable learning experience was a May 2022 Maymester trip to the Balkans to study folk medicines, an educational experience that brought him and his classmates even closer. “Being able to learn about pharmacy and pharmacology from a different perspective was extremely eye-opening,” Saville noted.

Saville contributes to the close-knit culture. “He has a big heart, though he pretends otherwise, and cares deeply for his family, friends and classmates. He looks out for those around him,” said Church, faculty leader of the 2022 Maymester trip. “His smile is goofy and genuine; it is endearing and can lighten tense moments or brighten the gloomiest situations.”

After graduation, Saville will travel to Norfolk, Va., to complete required training and then head to San Diego, Calif., to serve as a surface warfare officer aboard the USS Pearl Harbor.

He said he eventually hopes to earn a law degree and combine his pharmacy knowledge with legal skills. Saville is interested in becoming an attorney in a pharmacy-related field and believes the knowledge and skills he learned at USC Mann will serve as a solid foundation for his future endeavors.

“Being a freshman at a new school can be extremely daunting, but if you put yourself out there and get involved as much as you can, you will find your place here,” Saville said. “The USC Mann staff and professors are some of the nicest human beings in the world, and will help you discover what you want to do in your career and will also help you develop as a student.”

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Jack Saville, who is graduating from @USCMann with a bachelor’s degree in pharmacology and drug development, will soon commission in the U.S. Navy.
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Jack Saville
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Saville and his peers standing in front of a Navy helicopter on July 19, 2022.
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Saville and USC Mann classmates, faculty and staff during the “Maymester” trip in Romania on May 28, 2022.
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Keck School of Medicine of USC Dean Carolyn Meltzer beats impostor syndrome


Editor’s note: Title IX — the landmark legislation that prohibits sex discrimination in educational institutions that receive federal funding — was signed into law on June 23, 1972. In recognition of this anniversary, we’ll be profiling Trojan Title IX trailblazers throughout the year.


As a student at the Johns Hopkins University School of Medicine in the 1980s, Carolyn Meltzer remembers being plagued with feelings of impostor syndrome — especially each time she walked by the famous portrait of the university’s founding physicians known as “The Big Four.”

Title IX logo“It was where men are men and giants walk the halls,” she said. “If you were a woman, you were a bit of an outlier. My frame of mind was always to fit in with the guys and be twice as good to be recognized.”

Meltzer, dean of the Keck School of Medicine of USC and the May S. and John H. Hooval Dean’s Chair in Medicine since 2022, describes those years as “an arduous journey” that she had to push through. Only one-third of her classmates were female, and positive reinforcement was hard to come by.

“I remember a moment when I was a senior medical student and a female chief resident said to me, ‘You know, you’re really talented. You really do a good job,'” Meltzer said. She was speechless, and the chief resident wondered why. “I said, ‘Nobody has ever told me that since I’ve been here.'”

Speaking out to help others

These are among the experiences that inform Meltzer’s work overseeing the operations and academic affairs of Keck School of Medicine and its 16 major research institutes and 26 basic and clinical academic programs. She is mindful that it remains more common for women and other underrepresented and marginalized groups to doubt their abilities despite successfully performing at a high level.

When you’re early in your career … it’s very hard to speak up for yourself.

Carolyn Meltzer, Keck School of Medicine

“It’s only as I’ve gotten more senior that I’ve been able to speak out, to maybe be able to help others,” she said. “When you’re early in your career and at the bottom of the power and privilege gradient, it’s very hard to speak up for yourself.”

Meltzer has done a lot of work in the diversity space and has often heard people talking about impostor syndrome as if it were a character flaw that people need to get over.

“There’s a big part of our environment that helps create it,” she said. “Speaking now as a senior leader, we have to create environments that ensure people are feeling included and valued for the identities they bring to the table.”

Despite any self-doubt she battled as a student, Meltzer believed in equal opportunity “from a pretty young age” and “didn’t see a reason I shouldn’t be able to do anything the guys could do.”

Early role models

Meltzer earned her undergraduate degree with honors from Cornell University, where she was president of the Women in Medicine club and would try to find female physicians to come and share their experiences with students.

At Johns Hopkins, she was influenced by Catherine D. DeAngelis, a professor and physician who went on to become vice dean for academic affairs and faculty at the university and the first woman editor in chief of the Journal of the American Medical Association.

“Some of those giants who walked the halls were women,” Meltzer said. “Not too many, but just their presence had a great impact on me.”

Meltzer became an expert in neuroradiology and nuclear medicine and has conducted research to understand the structure and function of the brain during normal aging, dementia, Alzheimer’s disease and psychiatric disorders later in life. She also specializes in cancer imaging research.

“I went into a field that was very male-dominated with a lot of technology, innovation, PET [positron emission tomography] imaging and research areas — just very physics-heavy,” she said. “We still struggle with having women go into the hard sciences at equal rates.”

Meltzer was recruited to Keck School of Medicine after spending 15 years at Emory University School of Medicine, where she was chair of the department of radiology and imaging sciences. She also served as executive associate dean of faculty academic advancement, leadership and inclusion and as chief diversity and inclusion officer.

Meltzer had earlier held various academic and administrative appointments at the University of Pittsburgh School of Medicine, including creating and leading the school’s clinical PET center.

Protecting hard-earned rights

Although she wasn’t yet in high school when Title IX went into effect, Meltzer is grateful for the law and the protections it provides.

“It often takes federal legislation to put a stake in the ground and move the world forward, whether it’s civil rights or gender rights,” she said. “I don’t think we would have made as much progress in higher education and created as many opportunities for diverse individuals if Title IX hadn’t become law when it did.”

Progress is not linear, and it tends to be made by a series of tipping points. Then there are also moments where things slip back.

Carolyn Meltzer, Keck School of Medicine

While she celebrates Title IX’s 50th anniversary, Meltzer remains very concerned about gender equity overall in the United States, including women’s reproductive rights, the rights of the transgender community and the rights of professionals who provide gender-affirming care.

“Progress is not linear, and it tends to be made by a series of tipping points,” she said. “Then there are also moments where things slip back. I feel like we’re in a moment where there are both tipping points and slides back happening at the same time.”

Meltzer is working to make sure these setbacks don’t happen at USC.

“I think it’s a very optimistic place through the lens of Title IX,” Meltzer said. “I work with some wonderful women leaders and men leaders, and we’re trying to build a diverse team to give more voice to the complexity of the problems we’re focused on.”

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Biosimilar drugs underused due to commercial insurance restrictions

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Biosimilar Drugs Underutilized Due to Commercial Insurance Restrictions

First study to examine biosimilar drivers finds commercial insurers limit use in almost 20% of cases; restrictions greatest for pediatric patients.
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Biosimilars provide the same therapeutic benefits at much less cost than biologic medications, yet slow marketplace acceptance has prevented their advantages from being fully realized.

A new study led by USC Schaeffer Center Fellow Jakub Hlavka finds insurers either excluded or imposed restrictions on biosimilars in 19.4% of the cases examined. The study, published in the journal BioDrugs, is the first to address the drivers of biosimilar coverage.

Coverage limitations may take the form of step-therapy requirements that keep biosimilars away from patients until after other treatments have failed. In traditional pharmaceuticals, such exclusions are usually aimed at more expensive treatment options, however, in the case of biosimilars, their list prices tend to be lower than those of their reference products.

Hlavka worked with James Chambers, associate professor at Tufts Medical Center, and students from the USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences and USC Dornsife College of Letters, Arts and Sciences Department of Economics to examine 1,181 coverage decisions made by 17 U.S. commercial plans. The research included 19 commercially available biosimilars that provide alternatives to seven biologic reference products used in treating 28 different conditions.

Five of the plans–or 29.4% of the total–restricted biosimilar use in 30% or more of their decisions.

“These restrictions hamper the potential of biosimilars to increase access to care,” says Hlavka. He adds that, “such coverage variations may negatively impact patient access to effective treatments.”

The researchers find the following trends related to coverage decisions:

While plans were more likely to allow biosimilars for cancer patients, they were generally more likely to impose restrictions on biosimilar use for pediatric patients.
Coverage decisions were also found to be influenced by market competition and budget impacts: the first biosimilars to enter the market were less likely to have restrictive coverage and biosimilars offering savings of $15,000 or more per patient annually were much less likely to be restricted. Furthermore, the availability of cost-effectiveness evidence correlated significantly with coverage being less constrained.
Health plan pharmacy benefits managed by the three largest pharmacy benefit managers–CVS Caremark, Express Scripts, and OptumRx–were less likely to impose restrictions on biosimilar coverage relative to plans not managed by the big three.
The researchers note that many competing factors may be driving these trends: plans may be more cautious when it comes to pediatric patients while large PBMs may be leveraging their market power to negotiate higher rebates from biosimilars.

“We know that biosimilars are not being utilized as much as they could be,” says Hlavka. “Our study helps to uncover some of the trends in coverage decisions and offers points in the system where more research is warranted.”

Although brand biologics and specialty medicines account for just 3% of all prescriptions, they constitute 55% of all drug spending. Therefore, biosimilars have the potential to greatly increase savings while reaching greater numbers of patients with effective therapies for a wide range of diseases, from cancer to rheumatoid arthritis.

“Insurer coverage policies have a determining role in patients’ access to biosimilars. This study sheds light on the factors that influence insurer decision-making and provides novel insights into when patients have favorable access to biosimilars,” adds Chambers.

While Hlavka and his co-authors acknowledge that more research is needed, this study takes an important step in uncovering the decisions that result in a slower adoption of lower-cost equivalents of expensive biologic treatments.

Funding for this study was provided by a grant from the PhRMA Foundation. Tianzhou Yu and Shihan Jin of the USC Mann School and Chang Li of the USC Dornsife College of Letters, Arts and Sciences coauthored the study.

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Nursing graduate seeks to improve rural access to health care

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Nursing graduate seeks to improve rural access to health care

Raelene Zamora, MSN ’23, knows first-hand how daunting access to medical care can be in small, rural communities.
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According to the National Institutes of Health, rural Americans are more likely to die prematurely from heart disease, cancer, lung disease and stroke, and have higher rates of obesity and diabetes. They are also at greater risk for fatal car crashes, suicide and drug overdoses. Raelene Zamora wants to change this for her community of Porterville, California, and receives her Master of Science in Nursing (MSN) from the USC Suzanne Dworak-Peck School of Social Work in May 2023.

For Zamora, who grew up in the small Central Valley town, medical care in her community has always been daunting. It was normal for her to wait all day to be seen at a local clinic, and there was a period of months when she drove 55 miles for her daughter to see a specialist. Many residents of Porterville are living under the poverty line, so having to travel long distances for medical treatment is unrealistic.

“The commute could set some families back in their rent, work, food and day-to-day expenses,” Zamora said. “Especially if they are missing work to make the appointment.”

Zamora’s path to earning her MSN and becoming a family nurse practitioner has been challenging. She dropped out of high school, and unexpectedly became pregnant when she was 19. It was then she decided to go back and get her high school diploma. For the next 13 years, Zamora raised her daughter alone, earned her associate’s degree in nursing, and after passing her boards, began work at the local hospital, first as a preoperative nurse and now in the Intensive Care Unit (ICU).

At the hospital, Zamora cares for seriously ill patients. It was her experience there, coupled with those of her family living in the community, that inspired her to pursue an advanced degree in nursing.

Janett Hildebrand, associate teaching professor in the Department of Nursing at USC Social Work, explains that in rural communities like Zamora’s, social determinants of health play a significant role in health disparities and inequities. Obstacles like lack of transportation, literacy skills, access to a primary care provider during non-working hours and the necessity to travel long distances for care are common.

“These circumstances lead to delay in care, thus, patients may be sicker when they seek medical care,” Hildebrand said.

Zamora watched, helplessly, as a close aunt passed away from an end-stage cancer. “It could have been caught sooner, but the local clinic doctors kept turning her away,” she said. “I want to be able to recognize something like that and maybe take it a little more seriously in terms of thinking outside the box for any patient, no matter if they’re young or old, to look at all the possibilities it could be.”

She followed her heart

Zamora enrolled at USC and was able to take advantage of the flexible hybrid model of the MSN program while continuing to work at the ICU in Porterville. Classes are online, but live, allowing for interaction with professors and classmates in real-time. The small class sizes allowed the students to really get to know each other and Zamora says they still keep in touch. And as a self-proclaimed lover of learning, she appreciated the challenging and fulfilling local clinical placements for her required internships.

Hildebrand explains that these clinical experiences prepared Zamora to integrate the social determinants of health domains into her practice to provide high-quality comprehensive care to people with acute and chronic diseases.

“When she spoke in class, there was an excitement in her voice about her future role as a practitioner,” Hildebrand said. “She was aware of the disparities as an inpatient nurse, but now she was able to see how her role as a nurse practitioner could make a difference in the lives of patients such as the prevention of hospitalization. Her enthusiasm was reflected in her storytelling of the patient cases.”

As health care in rural areas across the country suffer from a shortage of doctors, particularly specialists, there is limited access to state-of-the-art equipment and an increasing number of health system closures due to lack of funding, Zamora wants to help make access to health care a priority in Porterville. It is where she grew up, her family is there and she sees the greater community as her extended family. She wants them all to have the same access to medical care as those in bigger cities, which would provide better patient outcomes by cutting out delays in patient care.

“I see my MSN providing me with the opportunity to sit down and thoroughly educate my patients,” Zamora said. “This is the main reason I chose to pursue my MSN to become a family nurse practitioner, to be able to have the opportunity to prevent someone from ending up in the ICU. To educate, follow-up and be someone the patient can see as a trusted provider, not just another provider.”

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Air pollution particles trigger cellular defense mechanisms

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Air pollution particles trigger cellular defense mechanisms

New research from the Keck School of Medicine of USC shows that air pollution particles activate a cellular defense mechanism known as autophagy, which may reduce the ability of cells to fight off other harms.
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The link between air pollution and lung disease has long been recognized. Now a new USC study reveals one biological process that may be behind that link — a discovery which could provide new insights on better ways to treat or prevent diseases related to pollution exposure.

“We know that diseases, especially lung diseases, can result from air pollution exposure. What we don’t know are the mechanisms by which that occurs,” said Edward Crandall, PhD, MD, professor of pathology, member of the Hastings Center for Pulmonary Research and director of the Will Rogers Institute Pulmonary Research Center at the Keck School of Medicine of USC.

In their research, Crandall and his team discovered a key step along the path between air pollution exposure and disease. Exposure to ambient nanoparticles, or very small pollutants in the air, limits the ability of cells to defend themselves against other potential harms. The findings were published in the journal Autophagy Reports.

Crandall, the study’s senior author, and his colleagues studied a cellular defense process known as autophagy, which cells use to destroy damaged or abnormal internal materials. For the first time, the researchers found that, when exposed to nanoparticles, autophagy activity in cells seems to reach an upper threshold.

“The implication of these studies is that autophagy is a defense mechanism that has an upper limit, beyond which it can’t defend the cell any further,” Crandall said.

An upper threshold

The researchers conducted a series of tests using lung adenocarcinoma cells. They first exposed the cells to nanoparticles, then to rapamycin (a chemical known to stimulate autophagy), then to both nanoparticles and rapamycin. In every case, autophagy activity reached the same upper threshold and did not increase further.

Consequently, cells may lack the ability to further boost autophagy to defend against other dangers, such as smoke inhalation or a viral or bacterial infection. This may help explain why air pollution increases a person’s risk for a number of acute and chronic lung diseases, including lung cancer, interstitial pulmonary fibrosis, and chronic obstructive pulmonary disease.

As part of the research, Crandall and his team also developed a new method of studying autophagy, which can support future studies on the subject. They used a combination of fluorescent dyes and a powerful imaging method, known as confocal microscopy, to document the amount of autophagy taking place inside individual cells.

“What’s special is that we can now measure the autophagic activity of single living cells in real time. It’s a novel method for studying autophagy,” said Arnold Sipos, MD, PhD, assistant professor of research pathology at the Keck School of Medicine and the study’s first author.

More research on autophagy

The new findings can help support ongoing research on autophagy, including for cancer treatment. While autophagy is a boon for healthy cells, it makes cancer cells harder to destroy. Developing methods to raise or lower autophagy in cells could be a key way to protect against and treat disease.

“The more we know about the mechanisms by which diseases occur, the more opportunity we have to find places in the pathway where we can intervene and prevent or treat the disease,” Crandall said.

Next, Crandall, Sipos and their colleagues will conduct further research to test whether adding nanoparticles to a cell directly increases its vulnerability to other threats, such as an infection. They plan to study the link in both healthy cells and cancer cells.

About this study

In addition to Crandall and Sipos, the study’s other authors are Kwang-Jin Kim of the Department of Pathology, Keck School of Medicine of USC and the Department of Biomedical Engineering, USC Viterbi School of Engineering and Constantinos Sioutas, Department of Civil and Environmental Engineering, USC Viterbi School of Engineering.

This work was supported by the Will Rogers Motion Picture Pioneers Foundation; Whittier Foundation; Hastings Foundation; and the National Institutes of Health [R01ES017034, U01HL108364, P01AG055367].

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Trailblazer Elyn Saks sees ‘gender-inspired mental health activism happening all the time now’

Editor’s note: Title IX — the landmark legislation that prohibits sex discrimination in educational institutions that receive federal funding — was signed into law on June 23, 1972. In recognition of this anniversary, we’ll be profiling Trojan Title IX trailblazers throughout the academic year.

When Professor Elyn Saks was a college student in the mid-1970s, she was in the minority. At Vanderbilt University, where she studied philosophy with a minor in ancient Greek and graduated as valedictorian, 28% of students were women undergraduates. At the University of Oxford, where she earned a master’s degree in philosophy on a prestigious Marshall Scholarship, one-third of the students were women — and all of her professors were men.

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Saks had the full support of her parents — “There was never any sense that as a woman I could not earn multiple degrees and have a good career,” she said — and she recognizes that when she was hired as a professor at the USC Gould School of Law in 1989, she was on a path that had been forged by Title IX, passed in 1972.

“Title IX is an extremely important law that changed the rights of women, and others, to participate fully in government, work and education,” Saks said. “When I started working at Gould in 1989, we were aware of the rights and interests of all groups. Since that time, it is great to see that more women are professors and students at USC.”

Saks, founder and faculty director of the Saks Institute for Mental Health Law, Policy and Ethics, went on to Yale Law School. During this time, she was diagnosed with schizophrenia, which presented the greatest personal challenge of her life, eventually guiding her toward a distinguished career in mental health advocacy and scholarship. That includes writing the groundbreaking 2007 memoir The Center Cannot Hold: My Journey Through Madness, which earned wide acclaim and made the New York Times Best Sellers list. In 2009, Saks was awarded a MacArthur Foundation Fellowship, aka the “genius grant,” which she used to launch the Saks Institute.

Saks’ interdisciplinary career intersects fields of law, public policy, and mental health research and advocacy, which is no surprise considering her life experiences.

Finding her calling

Diagnosed with depression while at Vanderbilt, Saks’ symptoms became more intense at Oxford. Her studies were interrupted by a monthslong stay in a psychiatric hospital, which she kept from her family for fear of worrying them. While hospitalized, she realized that being alone in a hospital room did not improve her condition. Studying and being with friends anchored her. Saks’ doctors agreed and let her get back to her studies at Oxford.

After earning her master’s degree, Saks, who had considered pursuing philosophy but realized her analytic thinking processes were more suited to law, began law school at Yale. Saks says her knowledge of Title IX became more prominent while at Yale, which is when she had returned to the states after five years. “Yale Law was also very keyed into civil rights and civil liberties,” Saks said. “It was common knowledge that Yale Law students went on to become professors or public interest lawyers.” Saks began incorporating mental illness topics into her student papers. One of the first was about how painful and degrading mechanical restraints in psychiatric hospitals were. She was shocked at her professor’s reaction to the paper.

“He said, ‘You don’t understand, Elyn. These people are psychotic. They don’t experience restraints as we would,'” she said. “It was only by ‘othering’ us that this professor could feel OK about doing to us what he never would want done to himself or loved ones.”

At Yale, Saks was eventually hospitalized and diagnosed with chronic schizophrenia. From her 2012 TED Talk, “A Tale of Mental Illness,” she mentions her “grave” prognosis as a woman with schizophrenia was not hopeful, according to the doctors. “At best, I was expected to live in a board-and-care [facility] and work menial jobs,” Saks said.

A community of support

Saks says mental illness treatment has certainly changed over time. For years, many women could be institutionalized for simply standing up for themselves or being “difficult.” Saks was fortunate that her family and friends believed in her abilities and supported her efforts to treat her mental illness and succeed academically.

“Many women were put in hospitals by their husbands for terrible reasons,” Saks said. “When I developed serious mental illness and was expressing pessimism about my future life and career, my father’s response was that people with serious cancer overcome their prognosis, and there was no reason to think I couldn’t overcome mine.”

After receiving her law degree, Saks worked as a staff attorney at a legal services agency in Connecticut but found it unfulfilling. She decided that her goal was to become a law professor.

“I truly enjoy introducing the next generation of students to the joys of thinking and writing about important societal issues,” Saks stated. “As a law professor, you can choose what you spend your time on. I love writing books and articles in my area of law and mental health.” When Saks joined the USC faculty in 1989, the university had only six female law school professors. As of 2022, there were 26 female professors.

Fighting mental health stigma

The Saks Institute is a think tank that studies issues at the intersection of law, mental health and ethics. The Saks Scholars, a yearly cohort of graduate students from various USC schools, spotlight one important mental health issue per academic year in a collaborative effort with faculty. Even within the institute, Saks has seen a decrease in mental health stigma over the years, which promotes more positive and open discussion about mental illness.

Because of Title IX, I believe things are getting better.

Elyn Saks, USC Gould

“Over 10 years, 80% of the Saks Scholars had disclosed in their application that they or a loved one had mental illness. When we first met as a group and we went around the room to discuss why they wanted to be a scholar, only one person self-disclosed,” Saks said. “Quite surprising for law students who were about rights, liberty and dignity. But, within the last year, almost everyone self-disclosed, including one woman who said she’d never mentioned to anyone that she had bipolar I with psychotic features.”

Saks is also encouraged by changes in terms of gender equality.

“Because of Title IX, I believe things are getting better. We see that in my area of research, mental health and mental health law,” Saks said. “We see gender-inspired mental health activism happening all the time now.”

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From first-gen student to master’s and doctoral degrees — and graduate student leadership


Commencement Spotlight: Samuel Garza

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Commencement Spotlight: Samuel Garza

The 2023 Mann School Graduate Speaker went from being a first-generation college student to pursuing doctoral and master’s degrees–all while serving as president of USC’s Graduate Student Government.
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Samuel Garza went from being a first-generation college student to earning his PhD in Molecular Pharmacology and Toxicology alongside a master’s in Regulatory Science at the USC Mann School of Pharmacy and Pharmaceutical Sciences. He also worked as a graduate research assistant while still finding time to advocate for more than 28,000 graduate and professional students as president of USC’s Graduate Student Government. Garza was the first-ever Mann School student to serve in the position.

Originally from the Inland Empire, Calif., Garza developed his passion for science at California State University, Los Angeles, where he earned a bachelor’s and a master’s degree in biology. From 2016 to 2018, he worked as graduate research fellow for Minority Opportunities in Research (MORE), a program funded by the National Institutes of Health that identifies highly motivated students and assists them in reaching their goals in obtaining doctoral degrees.

As his academic journey continued, Garza fell in love with biotechnology and pharmaceutical sciences while still an undergraduate. This led him to USC Mann–a school, in his words, that really positions students for success.

“Faculty and staff here are able to help you with whatever path you choose: academics, industry or government. There is always someone somewhere who can help you,” Garza said, referring to the school’s faculty and alumni network. “USC makes a promise and can keep that promise. This is unique to the university.”

At USC Mann, Garza conducted research in the lab of Dean Vassilios Papadopoulos. In this capacity, he co-authored several peer-reviewed academic publications with Papadopoulos and fellow researchers–including two featuring Garza as first author. Meanwhile, his thesis involved investigating the pathophysiology and treatment of conditions related to insufficient steroid hormone biosynthesis. He also worked as a drug discovery and development intern with Eli Lilly and Company.

During his first year at USC, Garza joined the USC Graduate Student Government, which represents master’s and PhD candidates in addressing important issues with university administration and faculty. The organization also offers a range of supportive resources–from interdisciplinary events and professional development resources to emergency funding and child support subsidies.

Garza was elected president for the 2022-23 academic year, serving as lead advocate for more than 28,000 graduate and professional students at USC. During his tenure, he spearheaded a university-wide study that led to an increase in stipend for PhD students. Garza and team members collected data from USC graduates, analyzed living expenses and peer school data, and made recommendations to the administration.

In August 2022, Garza addressed an audience of more than 8,000 at USC’s convocation ceremony. It was an exhilarating experience, he said. “I thought about my academic journey and how my experience might help others–especially how I got past the difficult moments throughout my journey. When I arrived at USC, I felt anxious and overwhelmed by the academic pace and new environment. But one thing kept me grounded: my acceptance letter. So, as I said to my fellow students that day, ‘Whenever you are feeling overwhelmed, think back to that acceptance letter,’ because by gaining admission to USC, we’ve all accomplished something incredible.”

Garza is currently considering roles in pharmaceutical consulting and development. To build on the scientific and regulatory expertise honed at USC Mann, he also plans to explore strategic leadership opportunities, including examining how data can be used to drive what happens next in the fields of pharmacy and pharmaceutical sciences.

Samuel Garza will address the graduates at the 116th USC Mann Commencement on Saturday, May 13, 2023.

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