New USC/Children’s Hospital Los Angeles lab to accelerate next-gen cell therapy

Published January 27, 2023

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New USC/CHLA cGMP Lab opens to accelerate next-generation cell therapy

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New USC/CHLA cGMP Lab opens to accelerate next-generation cell therapy

A new laboratory designed to advance early-stage research into lifesaving, commercially viable therapies was celebrated on the USC Health Sciences Campus Tuesday night.

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Housed at the USC Norris Comprehensive Cancer Center, the USC/CHLA cGMP Laboratory will manufacture cell and gene therapies under the Food and Drug Administration’s good manufacturing practice (cGMP) standards.

Therapies developed in the lab could one day be used to treat diseases such as arthritis, blindness and diabetes.

The 3,184-square-foot facility offers cleanrooms, laboratory space, cryostorage and state-of-the-art equipment for manufacturing and analytical testing. It was launched through a partnership between Children’s Hospital Los Angeles, Keck Medicine of USC and the Keck School of Medicine of USC.

The lab’s collaborative structure, broad expertise, specialized resources and regulatory knowledge will help accelerate big ideas and positive “disruption” to health care, said USC President Carol L. Folt, PhD.

“Effective partnerships can facilitate these breakthroughs while also supporting the steady, incremental and absolutely critical advancements” necessary to move an idea from lab to bedside, Folt said. “Billions of lives across the world could be changed by this work.”

Keck School of Medicine Dean Carolyn Meltzer, PhD, who began her position in March 2022, praised the countless hours teams spent bringing the idea to life.

“I came here because this institution really embodies interdisciplinary collaboration to solve the tough problems,” Meltzer said. “And this is a moment where we’re well positioned for disruptive growth and impact, which is really what’s most meaningful.”

The partnership demonstrates continued “representation of what world-class organizations can do working together,” said Paul Viviano, president and chief executive officer of CHLA, noting that his institution and USC have maintained an affiliation since 1932. “This magnificent center is a major step forward.”

The lab is part of a larger effort — the USC/CHLA Cell Therapy Program — to advance the science and translation of cell therapies at both institutions. (The program is tied to the USC+CHLA Alpha Clinic, which in November 2022 was awarded a five-year, $8 million grant from the California Institute for Regenerative Medicine.)

This effort marks continued momentum for expanding precision medicine. The cGMP lab’s multidisciplinary teams will work to further leverage the power of modified cells — as seen in CAR T-cell therapy, which reengineers patients’ immune cells to fight their own blood cancers — and apply them in new ways.

“The great thing about cell therapy is that patients are not passive receiving treatment; they are active participants,” said Mohamed Abou-el-Enein, MD, PhD, MSPH, executive director of the USC/CHLA Cell Therapy Program and director of the new cGMP lab.

The facility, he added, is “the missing puzzle piece that can enable us to bring homegrown discoveries to the clinic and to our patients.”

Abou-el-Enein expects the lab to serve 200 patients annually and partner with leading biotech companies. He also intends for it to help train a new generation of scientists and to prioritize pediatric and East Los Angeles patient populations.

Housing multiple parts of the development process under one roof offers a distinct advantage for researchers and patients, said Rod Hanners, chief executive officer of Keck Medicine.

“Cell-based therapies represent a quantum change in medical treatments,” Hanners said. “The establishment of the Translational Cell Therapy program between Keck Medicine of USC, Keck School of Medicine of USC and Children’s Hospital of Los Angeles, including the new cGMP facility, provides the collaboration, expertise and infrastructure to take new therapies and move them into clinical trials — all with the promise of curing diseases that affect our patient population.”

— Kevin Joy

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Americans don’t know what’s a healthy blood pressure — and that’s a problem

Published January 26, 2023

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False Confidence in Blood Pressure Knowledge Undermines Intentions to Seek Care

Most Americans don’t know the meaning of 120/80 mm Hg, but think they do — and that’s a potential problem for their health.

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Nearly half of adults in the U.S. have high blood pressure (hypertension). In the long run, high blood pressure damages blood vessels, increases risk of heart failure, and leads to other poor health outcomes, especially in patients with additional conditions such as heart disease, kidney disease and diabetes. High blood pressure is more common as we get older, and a majority of people will develop blood pressure in their lifetime.

Yet, almost two-thirds of adults do not know the upper thresholds for normal or healthy blood pressure, according to a survey a new USC study published this week in the journal Medical Decision Making.

“High blood pressure usually has no symptoms,” said Wandi Bruine de Bruin , who co-directs the Behavioral Sciences program at the USC Schaeffer Center for Health Policy & Economics and is provost professor of public policy, psychology and behavioral sciences at the USC Price School of Public Policy. “So it is important to have your blood pressure tested, and to take action if it’s too high.”

While most survey participants did not correctly identify the threshold for healthy blood pressure, Bruine de Bruin and her team found that the majority were overly confident in their knowledge of blood pressure readings – and this false sense of confidence may be undermining their intentions to seek care for stage 1 hypertension.

What blood pressure numbers mean and when to seek care
Blood pressure is measured with two numbers. The top number, called systolic blood pressure, measures the pressure in our arteries when our hearts beat. The second number is called diastolic blood pressure and measures the pressure in our arteries when our hearts are resting between beats.

According to the American Heart Association, there are five blood pressure (BP) categories:

Table explaining blood pressure categories
The American Heart Association recommends that everyone with stage 1 hypertension talk to their doctor about making lifestyle changes, including eating a low-sodium diet, limiting alcohol use, being more physically active, maintaining a healthy weight, managing stress and quitting smoking. Medication is recommended for people with stage 2 hypertension and for some people with stage 1 hypertension, including those who also have heart disease, kidney disease or diabetes.

Confidence outpaces knowledge of what constitutes normal/healthy blood pressure
Bruine de Bruin and colleagues surveyed 6,592 U.S. adults, including 1,342 who had hypertension without comorbidities (heart disease, kidney disease, and diabetes) and 795 who had hypertension with comorbidities. They assessed whether survey participants could identify the threshold for normal/healthy blood pressure as well as their confidence in understanding blood pressure numbers.

Among the whole sample, 64% of participants expressed confidence in their understanding of blood pressure numbers but only 36% stated that 120/80 mm Hg was the upper threshold for normal/healthy blood pressure. When counting 120-130/80 mm Hg as correct, it was 39%.

Participants with high blood pressure without comorbidities were also more likely to be confident (78%) than knowledgeable (47%), when counting 120-130/80 mm Hg as correct. The same was true for participants who had high blood pressure with comorbidities who were slightly more confident (81%) but less knowledgeable (40%).

The researchers suggest that this false confidence may stem from repeated exposure to a topic. “We tend to feel more confident about topics that are more familiar. And blood pressure feels like a familiar topic because it gets measured at pretty much every healthcare visit,” says Bruine de Bruin. “But if these blood pressure measurements are not explained well or at all, we may develop false confidence. And that false confidence makes is feel that we know when to seek care, even when we don’t.”

Indeed, the researchers find that this false confidence in understanding blood pressure readings may undermine intentions to seek care. Survey participants who were confident were more likely to express intentions to act on stage 2 hypertension readings, but less likely to express intentions to act on stage 1 readings compared to those who were not confident.

“Identifying, treating, and controlling high blood pressure is a major clinical and public health challenge,” says coauthor Mark Huffman, professor of Medicine at Washington University in St. Louis. “We know that the earlier patients seek and receive treatment, the better and easier it is to control their blood pressure.”

Every doctor’s visit is an opportunity to talk about blood pressure
“Blood pressure is measured every time we go to the doctor as well as the dentist and other medical offices,” said Bruine de Bruin. “But knowledge about what these blood pressure numbers mean is not being transferred from the provider to the patient.”

It’s not clear why doctors skip opportunities to talk about managing high blood pressure. Possibly, doctors are desensitized to seeing stage 1 hypertension. High pressure is very common among adults across the U.S. Some people also have elevated blood pressure readings due to the stress or anxiety of being at a doctor’s office, which may lead doctors to take no action after seeing a high blood pressure reading.

But lowering blood pressure can help people stay healthy. In fact, a recent study showed that lowering systolic blood pressure by 5 mm Hg through medication reduces the risk of major cardiovascular events by 10%. Providing patients with information about blood pressure levels and behaviors and treatments they can do is an easy way to improve health, explained the researchers.

In addition to Bruine de Bruin and Huffman, Yasmina Okan (Pompeu Fabra University and Centre for Decision Research, Leeds University) and Tamara Krishnamurti (Center for Research on Health Care, University of Pittsburgh) coauthored the study. The survey was administered through the Understanding America Study at the USC Dornsife Center for Economic and Social Research.

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Exactly how many senses do we really have?

Published January 19, 2023

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How Many Senses Do We Have?
If we think of our senses as limited to only five, we might be missing out.

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While the notion that people have five basic human senses is often considered a universal truth and can be traced back to Aristotle’s De Anima (On the Soul), many philosophers and neuroscientists are now debating whether we may have anywhere from 22 to 33 different senses.

Among these lesser-known senses are equilibrioception, which is associated with our sense of balance; proprioception, which enables us to know which parts of our bodies are where without looking; and chronoception, how we sense the passing of time.

And that’s just humans. “There are senses that other species have that we don’t, like directional senses and magnetic senses,” says Tok Thompson, professor (teaching) of anthropology. Iron oxide in the abdomen of honey bees, for example, can detect changes in the Earth’s magnetic field that enable them to navigate to their hive.

THE “X” SENSE

Then there is the hotly debated existence of the so-called “sixth sense.”

“The ‘sixth sense’ usually refers to an ‘unknown’ sense, but now that we know there are more than five senses, the idea could perhaps be better thought of as the ‘x sense,’ where ‘x’ equals the unknown — whether some yet undiscovered natural sense, or something more along the lines of psychic abilities,” says Thompson.

In some Indian philosophies, the mind, or “manas,” itself is considered a sixth sense that coordinates the five primary senses with other mental faculties.

Western societies generally equate the sixth sense with extrasensory perception — something that in Celtic culture is traditionally known as “second sight.” Among the supposed powers of those with the gift was the ability to predict death, even seeing fish scales (implying a watery grave) appear on someone they sensed would drown soon.

Do a little online digging into the sixth sense and you will find myriad claims of life-changing premonitions that appear to defy the idea that our five senses are our only faculties of perception.

Among them is the inner voice that Wall Street executive Barrett Naylor claimed saved his life — twice. According to a 2009 book about premonitions by physician Larry Dossey, Naylor was heading to work at the World Trade Center on Feb. 26, 1993, when something told him not to go into the building. Later that day, it was bombed. That same instinct, Naylor claimed, also saved him from the 9/11 terrorist attacks in 2001. But a belief in mystical, psychic abilities isn’t required to believe that our perceptions can extend beyond the physical senses.

“There are many layers to the mind,” says University Professor Antonio Damasio, professor of psychology,philosophy and neurology, and David Dornsife Chair in Neuroscience. “Facts, actions, feelings — all those contents can be retrieved, but are not equally accessible. Some are essentially shrouded in darkness, making conscious access to them difficult.”

As a result, Damasio notes, our unconscious mind can suddenly provide us with an answer when we least expect it.

“Intuition is not a myth; it calls attention to the richness of our minds,” he says.

ASSISTED VISIONS

Seeing what others don’t can sometimes require a catalyst. In many indigenous cultures, psychedelics are ingested to induce ecstatic experiences that bring revelations. The mushroom Psilocybe mexicana is regarded with such awe by Mexico’s indigenous communities that the Aztecs dubbed it “teonanacatl,” or “God’s Flesh.”

Visions, primarily those brought on by lysergic acid diethylamide, or LSD, have also been the focus of scientific study. A chemical compound accidentally invented by Swiss researcher Albert Hofmann in 1938, LSD induces powerful, emotional hallucinations.

Of course, LSD eventually found its way into the counterculture, and its ability to inspire visions of an interconnected world helped power the nascent environmental movement of the 1960s. However, the drug’s potent effects also triggered numerous tragic outcomes.

Researchers are now evaluating the potential for microdoses of other hallucinogenic substances such as psilocybin mushrooms to help people suffering from PTSD, depression and anxiety.

SEEING IS BELIEVING

Not all visions require chemical prompting, however. Catholic saints who claimed to have striking visual or auditory hallucinations often lived piously in religious orders. Saint Catherine of Siena is said to have had her first visitation from Christ at the age of 5 or 6. Those in deep, meditative states sometimes tell of encounters with light beings or other strange, visual phenomena.

Nowadays we might assume that these sorts of visions, if not induced by mind-altering substances, are the product of a brain disorder like schizophrenia. But even in medieval times, the church questioned the authenticity of such visions and imposed strict rules to evaluate a vision’s legitimacy.

“This is well before psychiatry, of course, but people living during this era still recognized crazy when they saw it,” says Lisa Bitel, Dean’s Professor of Religion and professor of religion and history. “If someone was mentally ill, their visions would not be taken seriously. You had to be well-regarded in the community and whatever you saw had to be doctrinally correct. A claim that you saw the Virgin Mary riding in on [the medieval equivalent of] a celestial skateboard wouldn’t be taken seriously.”

For the devout, the modern argument that seeing angels is actually evidence of insanity, or at the very least the result of an overactive imagination, appears absurd. The devout believe that a person who has spiritual visions has gained special access to the truth, not lost their mind. “They would say that the enlightened person is actually seeing things as they really are,” says James McHugh, professor of religion.

Visions are still a regularly occurring phenomenon, despite our supposedly more rational approach to the world, says Bitel. Today’s reported sightings of UFOs, sometimes said to be inhabited by celestial beings bearing wise words, might just be the descendants of yesteryear’s angels.

“Cultural terms may have changed, but the apparitions go on,” she says. “The visions we hear about are just the tip of the iceberg.”

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Researchers find music education benefits youth wellbeing

Published January 18, 2023

The latest USC research on the impact of music education shows that for adolescents, the benefits appear to extend beyond a surge in neural connections in their brains. It actually boosts their wellbeing.

The study published Wednesday by the journal Frontiers In Psychology comes just weeks after voters statewide approved Proposition 28 to increase funding for arts and music education in California public schools.

A USC Thornton School of Music researcher said the results are especially meaningful amid a nationwide mental health crisis.

“We know that the pandemic has taken a toll on student mental health. The many narratives of learning loss that have emerged since the start of the pandemic paint a grim picture of what some call a ‘lost generation,'” said Beatriz Ilari, a USC Thornton associate professor of music education and corresponding author of the study. “Music might be an activity to help students develop skills and competencies, work out their emotions, engage in identity work and strengthen connections to the school and community.”

The work was supported by grants including one from the Fender Play Foundation, a nonprofit organization that places instruments in the hands of youth who aspire to play and reap the powerful benefits of music education.

Evidence of those benefits continues to mount, although many states and school districts have reduced the amount of class time, faculty and curriculum dedicated to the arts amid budget crunches and changes in curriculum standards.

Ilari contributed to prior studies, including a longitudinal one by the USC Brain and Creativity Institute, that demonstrated children who learn a musical instrument have enhanced cognitive function. Other research also has shown music education contributes to improved creativity and confidence, better mental health and emotional stability, and student performance, according to a paper published last year by the International Journal of Environmental Research and Public Health.

Music education and hope for the future

For the study, researchers examined the impact of music on “positive youth development,” a measure of the strengths of adolescents and their potential to contribute to society developed by scholars from Tufts University. Researchers also included measures for school connectedness and hopeful future expectations.

The researchers administered anonymous, online surveys to 120 students from 52 Los Angeles Unified School District middle schools. The survey questions covered the key domains of positive youth development including competence and confidence. Past research shows that adolescents who manifest these attributes are more likely to make positive contributions to society and less likely to engage in risky behaviors later in life.

Ilari and her fellow researchers, including USC Thornton alumna Eun Cho, found many positive effects. They found that students who started music education before age 8 were more hopeful about the future, and younger students who received musical training scored higher in key measures of positive youth development.

The research team also found that younger students scored higher in key development measures than their older peers. Sixth-grade students, for example, scored higher for overall positive youth development than eighth graders, and scored higher in the confidence domain than both seventh- and eighth graders. Seventh grade students also scored higher in overall positive youth development than eighth graders.

In completing the study’s survey questions, students were invited to choose from multiple gender categories beyond the usual binary gender options, including “non-binary” and “prefer not to answer,” to identify themselves. Non-binary students scored lower in overall positive youth development and connection than girls. They also scored lower in confidence and connection than boys.

Our study can be used to inform the development of programs and policy for all young people.

Beatriz Ilari, USC Thornton

“Given the high levels of depression and suicide ideation among LGBTQ+ and non-gender-conforming students, it is crucial that research examining adolescent well-being move beyond the gender binary,” Ilari said. “In addition to filling critical gaps in the existing literature, results from our study can be used to inform the development of programs and policy for all young people.”

The study included students of diverse backgrounds. However, students participating in a virtual music education program primarily came from poor neighborhoods, indicating disparities in access to formal music education.

In addition, the study explored students’ engagement in different music programs, including the Virtual Middle School Music Enrichment (VMSME), a tuition-free, extracurricular program that focuses on popular music education and virtual learning. The program is available through a school district partnership with the Fender Play Foundation. Researchers found that students participating in multiple forms of music education and for longer periods of time scored higher in measures for competence and hopeful future expectations. Some participants in these groups were also enrolled in private lessons and/or playing in small ensembles that offer more individual attention than large group classes. In contrast, students in the extracurricular enrichment program came from low-income neighborhoods and participated in fewer extracurricular activities.

“By expanding access to instruments and music classes for students from low socioeconomic areas – a population that is often left out of school music programs – VMSME contributed to the democratization of music education,” Ilari said. “Throughout the pandemic, students in public schools, especially in urban areas, were disproportionately impacted by the lockdowns that deprived them of physical and social contact with peers. VMSME brought together students from different neighborhoods and at a time when forming peer groups is essential to social identity development.”

More research is needed to better understand disparities in access to formal music education, Ilari said, but she said programs that give student agency in their learning and allow them to engage with peers from other schools, like VMSME, have the potential to promote learning and well-being.

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USC study reveals the key reason why fake news spreads on social media

Published January 17, 2023

USC researchers may have found the biggest influencer in the spread of fake news: social platforms’ structure of rewarding users for habitually sharing information.

The team’s findings, published Monday by Proceedings of the National Academy of Sciences, upend popular misconceptions that misinformation spreads because users lack the critical thinking skills necessary for discerning truth from falsehood or because their strong political beliefs skew their judgment.

Just 15% of the most habitual news sharers in the research were responsible for spreading about 30% to 40% of the fake news.

The research team from the USC Marshall School of Business and the USC Dornsife College of Letters, Arts and Sciences wondered: What motivates these users? As it turns out, much like any video game, social media has a rewards system that encourages users to stay on their accounts and keep posting and sharing. Users who post and share frequently, especially sensational, eye-catching information, are likely to attract attention.

“Due to the reward-based learning systems on social media, users form habits of sharing information that gets recognition from others,” the researchers wrote. “Once habits form, information sharing is automatically activated by cues on the platform without users considering critical response outcomes, such as spreading misinformation.”

Posting, sharing and engaging with others on social media can, therefore, become a habit.

[Misinformation is] really a function of the structure of the social media sites themselves.

Wendy Wood, USC expert on habits

“Our findings show that misinformation isn’t spread through a deficit of users. It’s really a function of the structure of the social media sites themselves,” said Wendy Wood, an expert on habits and USC emerita Provost Professor of psychology and business.

“The habits of social media users are a bigger driver of misinformation spread than individual attributes. We know from prior research that some people don’t process information critically, and others form opinions based on political biases, which also affects their ability to recognize false stories online,” said Gizem Ceylan, who led the study during her doctorate at USC Marshall and is now a postdoctoral researcher at the Yale School of Management. “However, we show that the reward structure of social media platforms plays a bigger role when it comes to misinformation spread.”

In a novel approach, Ceylan and her co-authors sought to understand how the reward structure of social media sites drives users to develop habits of posting misinformation on social media.

Why fake news spreads: behind the social network

Overall, the study involved 2,476 active Facebook users ranging in age from 18 to 89 who volunteered in response to online advertising to participate. They were compensated to complete a “decision-making” survey approximately seven minutes long.

Surprisingly, the researchers found that users’ social media habits doubled and, in some cases, tripled the amount of fake news they shared. Their habits were more influential in sharing fake news than other factors, including political beliefs and lack of critical reasoning.

Frequent, habitual users forwarded six times more fake news than occasional or new users.

“This type of behavior has been rewarded in the past by algorithms that prioritize engagement when selecting which posts users see in their news feed, and by the structure and design of the sites themselves,” said second author Ian A. Anderson, a behavioral scientist and doctoral candidate at USC Dornsife. “Understanding the dynamics behind misinformation spread is important given its political, health and social consequences.”

Experimenting with different scenarios to see why fake news spreads

In the first experiment, the researchers found that habitual users of social media share both true and fake news.

In another experiment, the researchers found that habitual sharing of misinformation is part of a broader pattern of insensitivity to the information being shared. In fact, habitual users shared politically discordant news — news that challenged their political beliefs — as much as concordant news that they endorsed.

Lastly, the team tested whether social media reward structures could be devised to promote sharing of true over false information. They showed that incentives for accuracy rather than popularity (as is currently the case on social media sites) doubled the amount of accurate news that users share on social platforms.

The study’s conclusions:

Habitual sharing of misinformation is not inevitable.
Users could be incentivized to build sharing habits that make them more sensitive to sharing truthful content.
Effectively reducing misinformation would require restructuring the online environments that promote and support its sharing.

These findings suggest that social media platforms can take a more active step than moderating what information is posted and instead pursue structural changes in their reward structure to limit the spread of misinformation.

About the study: The research was supported and funded by the USC Dornsife College of Letters, Arts and Sciences Department of Psychology, the USC Marshall School of Business and the Yale University School of Management.

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Discoveries help bone marrow transplant recipients

Published January 17, 2023

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Why multipotent progenitor cells matter for patients receiving bone marrow transplants
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When patients receive bone marrow transplants, they are infused with complex admixtures of many different cell types with the power to regenerate their blood and immune systems. In a new study in Experimental & Molecular Medicine, scientists from the USC Stem Cell laboratory of Rong Lu share new discoveries about the influence of multipotent progenitor cells (MPPs) that are co-transplanted along with stem cells during bone marrow transplants.

“This is the first study to investigate the influence of MPPs, which we found stimulated stem cells to produce more T cells,” said Lu, the study’s corresponding author and an associate professor of stem cell biology, biomedical engineering, medicine, and gerontology at USC. “Improving T cell production in bone marrow transplantation can help prevent infections, a major complication that can be fatal for patients undergoing this treatment.”

In the study, first author Zheng Wang and his colleagues used genetic labels to “barcode” individual stem cells in bone marrow transplants in mice. The bone marrow transplants included MPPs along with blood-forming or “hematopoietic” stem cells (HSCs)–similar to what patients receive when being given bone marrow transplants to treat leukemia or other life-threatening conditions.

The scientists then tracked the blood production of the barcoded HSCs over a short-term period of 2.5 months and a long-term period of 6.5 months. When co-transplanted with MPPs, the HSCs produced many different cell types in the short-term, but ultimately increased their production of T cells in the long-term.

“The more we learn about these cellular interactions, the more we can inform clinicians about how to optimize bone marrow transplants for patients,” said Lu.

Additional co-authors include Du Jiang, Mary Vergel-Rodriguez, and Anna Nogalska from the Lu Lab.

The research was funded by the Chongqing Natural Science Foundation (cstc2019jcyj-msxmX0421), National Institutes of Health (R00-HL113104, R01HL135292, R01HL138225, and R35HL150826). Rong Lu is a scholar of the Leukemia & Lymphoma Society (LLS-1370-20) and was a Richard N. Merkin Assistant Professor.

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How to rewind the clock on arthritic cartilage

Published January 14, 2023

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How to rewind the clock on arthritic cartilage … stat!
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A new study in Aging Cell describes how a key protein, called Signal Transducer and Activator of Transcription 3 (STAT3), might turn back the clock on aging cartilage that leads to osteoarthritis.

“STAT3 performs an astonishing repertoire of roles in development and regeneration, as well as inflammatory disease and cancer. In this study, we found an innovative chemical approach for reversing aging of joint-forming cells in a clinically relevant manner, because this intervention is simple and fully controlled,” said the study’s co-corresponding author Denis Evseenko, who is an Professor of Orthopaedic Surgery, and Stem Cell Biology and Regenerative Medicine at USC, and holds the J. Harold and Edna LaBriola Chair in Genetic Orthopedic Research.

“We wanted to understand the role of STAT3 in cartilage cells during embryonic development as well as in the context of osteoarthritis,” said co-corresponding author Steve Horvath, a Professor of Human Genetics and Biostatstics at UCLA.

To accomplish this, first authors Arijita Sarkar, Nancy Q. Liu and their colleagues at USC and UCLA performed a series of experiments to uncover how STAT3 turns genes on and off through a process known as epigenetic regulation. Specifically, the team identified patterns of epigenetic regulation that correlate with the age of cartilage cells. These correlations served as the basis for creating what the researchers dubbed an “epigenetic clock” for cartilage cells.

By using a molecule to activate STAT3, they were able to reverse the hands of the epigenetic clock–turning on many genes and creating an epigenetic pattern typical of younger cartilage cells. When they genetically inactivated STAT3, the epigenetic clock ticked faster–turning off many genes and promoting an epigenetic pattern observed in older cartilage cells.

The scientists then focused their attention on an important enzyme called DNA methyltransferase 3 beta (DNMT3B), which interacts with STAT3. When STAT3 was inactivated, DNMT3B kicked into high gear to add aging marks to the DNA molecule, and promoted the progression of knee osteoarthritis in injured mice.

In the arthritic knee cartilage of the mice, there was a significant population of cartilage cells that appeared to be turning back time and reverting to an immature state.

“These cells may be assuming more embryonic-like state as an attempt to enhance their capacity to develop new knee cartilage,” said Sarkar, who is a postdoc in the Evseenko Lab.

Unfortunately, while these immature cells make cartilage that is youthfully regenerative during embryonic development or acute injury, they seemed to create cartilage that is dysfunctionally immature in the context of a chronic condition such as osteoarthritis.

“When present on a longer term basis, hyperactivation of the immature program in cartilage cells is likely to promote inflammation and, ultimately, degeneration and fibrosis,” said Liu, a senior scientist in the Evseenko Lab.

In the future, the results of this study can inform the quest to develop treatments that harness STAT3’s power to promote regeneration without tapping into its tendency to trigger inflammation.

Additional co-authors include Jenny Magallanes, Jade Tassey, Siyoung Lee, Ruzanna Shkhyan, Youngjoo Lee, Jinxiu Lu, Yuxin Ouyang, Hanhan Tang, Fangzhou Bian, Litao Tao, and Neil Segil from USC, and Jason Ernst and Karen M. Lyons from UCLA.

This work was supported by grants from the National Institutes of Health (R01AR071734 and R01AG058624), Department of Defense (W81XWH-13-1-0465), and the California Institute for Regenerative Medicine (TRAN1- 09288).

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How USC-led innovation can solve global challenges

Published January 12, 2023

With nearly $1 billion in actively funded research, USC is among the nation’s leading institutions for innovative, impactful discovery. Leading that effort is Ishwar Puri, who arrived at USC in 2021 and was recently promoted to senior vice president for research and innovation.

In the two years since his arrival, the university has continued to build on its research successes, winning major federal grants for research and innovation in computing, biomedical device and drug therapy development, medical research, as well as collaborative research projects with local governments and organizations that solve social problems and policy issues.

Puri has been charged with increasing interdisciplinary partnerships and speeding up discovery in an era of increasingly tech-dependent, rapid scientific inquiry. We spoke with the internationally recognized scientist and engineer about some of the past year’s major accomplishments, what might be in store for 2023 and how USC-led innovation can solve global challenges.

Congratulations on your new title. The most notable change is the addition of innovation under the umbrella of research. What does that new area of focus represent, practically?

Thank you, but really the story isn’t about me — it’s about USC President Carol L. Folt’s vision for the university since she arrived. During her time at USC, our sponsored research has increased at 7% annually, which would put us close to doubling that figure by 2028 or so. Money isn’t everything; it is trumped by impact. So, Dr. Folt has asked us to work toward audacious moonshots in areas such as computing and health. She has tasked us with improving our impact on society by developing innovative solutions for complex problems.

Money isn’t everything; it is trumped by impact.

Ishwar Puri

Innovation can take many forms. It can be through entrepreneurship, licensing to corporate entities and also thinking in a different way. If you think of sustainability, it’s not just about climate change research or providing solutions for electrification or other forms of renewable energy. Sustainability is about finding the kind of human solutions that will take us away from fossil fuel consumption. It’s finding environmentally friendly ways to eliminate or reduce waste. These are human problems, social science problems, health problems. That is where innovation comes in.

Practically, we are developing a partnership model of innovation and entrepreneurship. We are working with all our schools to help each of them flourish. We help them take their best examples and accelerate these through central means, including the Alfred E. Mann Institute, which is now part of the Office of Research and Innovation.

You mentioned an emphasis on research and innovation that is impactful. What are some examples of USC research that made an impact in 2022?

Due to the depth and breadth of expertise at USC, researchers across the university conduct impactful research every day. One example is our world-leading work in Alzheimer’s disease research. Publications (such as a recent one from Paul Thompson, Arthur Toga and Julie Zissimopoulos) have greatly expanded our collective knowledge of the causes and potential solutions for neurodegenerative cognitive diseases. In other areas, Kristina Lerman and Emilio Ferrara from the USC Information Sciences Institute examined the effects of polarization on social media users. Gale Sinatra co-authored a piece for The Conversation that examined how Hollywood perpetuates myths that fuel science skepticism. And earlier this year, Sergey Nuzhdin partnered with AltaSea at the Port of Los Angeles to open a massive 6,000-square-foot seaweed lab that will help grow the blue economy. These are just a few examples; there are countless others.

How is USC looking to expand its impact in 2023?

The president’s view is that if we’re really going to have an impact, it must be through partnerships. USC has very strong local community partnerships in environmental health, for instance. We’ve also started to form partnerships with area universities, notably with UCLA and Caltech, on grant proposals that combine the strengths of each institution to address complex challenges. In fact, USC is the lead partner of the new National Science Foundation Innovation Corps Hub: West Region, a consortium of engineers and scientists from top research universities in the Western United States. And because we are committed to developing a diverse talent pipeline, we are partnering with minority-serving institutions and community colleges through outreach activities and other partnerships. The president has insisted on and successfully developed a culture of collaboration among university leaders.

That emphasis on collaboration applies within the university as well?

Yes. Take entrepreneurship for example. When you think of entrepreneurship in the university setting, you typically think of the classic tech transfer model: Do some research, and then commercialize it. But the real talent at USC lies in the sheer number of our potential entrepreneurs. We have business-minded undergraduate and graduate students, postdocs and faculty members, and to support them we must meld research with experiential learning, where different parts of the university come together.

We do amazing discovery research. But maybe it’s not just the researcher who takes that work to fruition as a solution. Instead, it is a partnership with students, postdocs and others.

Ishwar Puri

We do amazing discovery research. But maybe it’s not just the researcher who takes that work to fruition as a solution. Instead, it is a partnership with students, postdocs and others. In partnership with the provost and the senior vice president for health sciences, the Office of Research and Innovation now works with deans to develop programs that take advantage of internal partnerships in different areas of the university. We cannot afford to segment or sector different areas because they are synergistic. The future lies in partnership and collaboration.

Speaking of the future, if you were a young researcher, why would you want to be at USC?

It really comes down to three things: excellence, scale and opportunity. Undoubtedly, USC offers excellence and hence we are a great attractor of talent. USC also offers scale. Where else in the world can one go to collaborate with leading scholars in communications, technology and cinematic arts? Not many other places. That school of schools model, and the scales of those schools, coupled with our excellence in health sciences, technology, humanities and the arts is a great launch pad for a young person’s career. In addition, the president’s expansive research vision for the university — increased partnerships; investments in internal support programs like internal grants, startups and mentoring; and her moonshots — provides young researchers with incredible opportunities to rub shoulders with experienced academics who have been in the business for a while and contributes to everyone’s success.

These all combine to make USC a very exciting place to work. I feel very fortunate to have the opportunity to be at USC and work with brilliant researchers across disciplines. This truly is an exceptional place with unrivaled talent and leadership.

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How old is your brain, really? Artificial intelligence knows

Published January 11, 2023

The human brain holds many clues about a person’s long-term health — in fact, research shows that a person’s brain age is a more useful and accurate predictor of health risks and future disease than their birthdate. A new artificial intelligence model that analyzes MRI brain scans developed by USC researchers could be used to accurately capture cognitive decline linked to neurodegenerative diseases like Alzheimer’s much earlier than previous methods.

Brain aging is considered a reliable biomarker for neurodegenerative disease risk. Such risk increases when a person’s brain exhibits features that appear “older” than expected for someone of that person’s age. By tapping into the deep learning capability of the team’s novel AI model to analyze the scans, the researchers can detect subtle brain anatomy markers that are otherwise very difficult to detect and that correlate with cognitive decline. Their findings, recently published in the journal Proceedings of the National Academy of Sciences, offer an unprecedented glimpse into human cognition.

“Our study harnesses the power of deep learning to identify areas of the brain that are aging in ways that reflect a cognitive decline that may lead to Alzheimer’s,” said Andrei Irimia, assistant professor of gerontology, biomedical engineering and neuroscience at the USC Leonard Davis School of Gerontology and corresponding author of the study.

People age at different rates, and so do tissue types in the body. We know this colloquially when we say, ‘So-and-so is 40, but looks 30.’

Andrei Irimia, USC Leonard Davis
School of Gerontology

“People age at different rates, and so do tissue types in the body,” Irimia said. “We know this colloquially when we say, ‘So-and-so is 40, but looks 30.’ The same idea applies to the brain. The brain of a 40-year-old may look as ‘young’ as the brain of a 30-year-old, or as ‘old’ as that of a 60-year-old.”

Brain aging: A more accurate alternative to existing methods

Researchers collated the brain MRIs of 4,681 cognitively normal participants, some of whom went on to develop cognitive decline or Alzheimer’s disease later in life.

Using these data, they created an AI model called a neural network to predict participants’ ages from their brain MRIs. First, the researchers trained the network to produce detailed anatomic brain maps that reveal subject-specific patterns of aging. They then compared the perceived (biological) brain ages with the actual (chronological) ages of study participants. The greater the difference between the two, the worse the participants’ cognitive scores, which reflect Alzheimer’s risk.

The results show that the team’s model can predict the true (chronological) ages of cognitively normal participants with an average absolute error of 2.3 years, which is about one year more accurate than an existing, award-winning model for brain age estimation that used a different neural network architecture.

“Interpretable AI can become a powerful tool for assessing the risk for Alzheimer’s and other neurocognitive diseases,” said Irimia, who also holds faculty positions with the USC Viterbi School of Engineering and the USC Dornsife College of Letters, Arts and Sciences.

“The earlier we can identify people at high risk for Alzheimer’s disease, the earlier clinicians can intervene with treatment options, monitoring and disease management.“

Brain aging: differences according to sex

The new model also reveals sex-specific differences in how aging varies across brain regions. Certain parts of the brain age faster in males than in females, and vice versa.

Males, who are at higher risk of motor impairment due to Parkinson’s disease, experience faster aging in the brain’s motor cortex, an area responsible for motor function. Findings also show that, among females, typical aging may be relatively slower in the right hemisphere of the brain.

An emerging field of study shows promise for personalized medicine

Applications of this work extend far beyond disease risk assessment. Irimia envisions a world in which the novel deep learning methods developed as part of the study are used to help people understand how fast they are aging in general.

“One of the most important applications of our work is its potential to pave the way for tailored interventions that address the unique aging patterns of every individual,” Irimia said.

“Many people would be interested in knowing their true rate of aging. The information could give us hints about different lifestyle changes or interventions that a person could adopt to improve their overall health and well-being. Our methods could be used to design patient-centered treatment plans and personalized maps of brain aging that may be of interest to people with different health needs and goals.”

The post How old is your brain, really? Artificial intelligence knows appeared first on USC News.

Tracking the pulse of the nation during a pandemic

Published January 11, 2023

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https://dornsife.usc.edu/news/stories/3805/unique-agile-survey-tool-tracks-pandemic-trends/
Story Headline and Deck – USC News *
Unique survey tool closely tracked the pulse of the nation throughout the COVID-19 pandemic

The Understanding America Study, created and managed by USC Dornsife’s Center for Economic and Social Research, enables researchers at USC and other institutions to quickly field timely surveys to the public.
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In the early, hectic days of the COVID-19 pandemic, government officials, scientists, researchers and the world at large were scrambling to understand (and contain) the virus. But some scholars were already turning their attention to how the crisis was affecting nearly every other facet of life, from young people’s mental health to students’ knowledge retention rates to the economic outlook for small business entrepreneurs.

One tool proved particularly useful for researchers to quickly gather and synthesize data on the pandemic: the Understanding America Study (UAS), based at the Center for Economic and Social Research (CESR) at the USC Dornsife College of Letters, Arts and Sciences.

The study comprises numerous surveys assessing public attitudes on a wide variety of topics, including health, work and finances, cognitive ability, physical activity and dietary habits, personality, and religion.

UAS comprises an internet panel of households created and managed by CESR to provide a flexible resource for researchers to quickly field timely surveys to the public. The panel totals about 10,000 people and provides a representative sample of adults in the nation. Statistical adjustments are provided to align the sample with the country’s population in terms of gender, age, race/ethnicity, education and geographic region.

“Respondents are invited by sending them letters through the U.S. mail and providing them with a computer tablet and free internet access if needed,” says Arie Kapteyn, CESR director and professor (research) of economics at USC Dornsife. “This avoids the biases of most popular internet surveys, which systematically miss the part of the population that has no internet access.”

Surveys gather data on the COVID-19 pandemic’s effects

Shortly after the nation’s pandemic lockdown began, CESR researchers began using UAS to assess the effects of the crisis in real time.

“We started administering surveys to parents asking about their children’s educational experiences by the end of March 2020. We were very fast but always careful about what we were asking and how we were asking it from the very beginning, which gave us high-quality data,” says Anna Saavedra, a research scientist at CESR.

Saavedra says that the longevity and scope of the UAS — the study was first launched in 2014, and dozens of surveys are ongoing at any given point in time — and its robust relationships with participating households are two key elements that made it a good tool for quickly gathering COVID-related data.

Marco Angrisani, assistant professor (research) of economics and one of the original developers of the UAS, adds that the survey was also designed to be “flexible” to allow for the rapid development and dissemination of new questions and topics, and has always worked to incorporate new technologies, such as apps, Fitbits and air pollution devices, that allow data to be gathered quickly.

“We aimed to make the surveys kind of fun and easy to administer, and to allow people to respond at their own pace — things that were really different from what other national studies were doing,” Angrisani says.

USC Dornsife program provides “warp speed” studies

UAS surveys are developed not only by USC faculty but also by researchers at other institutions. During the COVID-19 pandemic, many turned to the UAS to gather near real-time data on how the virus was affecting various facets of life.

One study, conducted by scholars in Florida, Michigan and France, and cited last fall in a New York Times article, assessed the long-term effects of the COVID-19 pandemic on the mental health of people younger than 30. Another, by a Spanish researcher, looked at gender differences in the risk perception of COVID-19. And The Wall Street Journal recently cited UAS data in an opinion piece.

Felix Kabo, formerly a member of the research faculty at the University of Michigan, Ann Arbor, and now the research director at CannonDesign, helped design a UAS survey on how pandemic-related government aid was distributed to Black-owned versus non-Black-owned businesses. He says he had been designing research on entrepreneurship before the pandemic, but the structure of the UAS allowed him to quickly pivot to looking at how the crisis was affecting businesses in real time.

“We realized very quickly that COVID was doing a number on small businesses and entrepreneurs, and we wanted to collect data on how it was affecting them in 2020; we didn’t want to wait until 2021 or later,” he says. “This is where the flexibility of the UAS really came into play for us because we were able to design an instrument in a month or two, and they were able to code it within a matter of a week or two. And by May or June 2020, we had our COVID-specific survey out in the field, gathering data. This may not sound like much, but it’s like warp speed in study years.”

Understanding American Study is made to make a difference

Because UAS data are publicly available, they are often consulted by researchers, government officials, private businesses and others. Saavedra says that one of her studies, about children’s academic achievement during the 2020-21 school year, was cited in correspondence between several U.S. Senators and former Senate Majority Leader Mitch McConnell. Another, regarding the effect of COVID on classroom learning, was cited by Orange County officials when they were trying to figure out an education plan for local students.

Now that the initial shock of the pandemic has passed, Saavedra adds, UAS studies are following long-term trends to gauge the crisis’ more lasting effects on mental health, learning and other educational aspects.

“We have asked a number of times about children’s participation in interventions designed to help mitigate the negative effects of the pandemic, like tutoring, summer school, mental health supports. And that work has gotten a lot of attention because it’s policy relevant — there’s $122 billion in American rescue plan spending, and a lot of it’s being spent on these interventions,” Saavedra says.

Angrisani adds that one of the core strengths of UAS is how accessible it is to a diversity of users. “Being able to connect with different spheres is important to what we want to do,” he says, and it enables the survey to make a difference in the larger world beyond academia.

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