In January 2021, Dodger Stadium was one of California’s largest COVID-19 vaccination sites, dispensing vaccines to up to 12,000 people daily.

Cars lined up throughout the stadium parking lot as volunteers and staff from USC, the Los Angeles Fire Department and the nonprofit Community Organized Relief Effort prepped doses for L.A. residents.

Throughout the pandemic, the USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences partnered with Keck Medicine of USC, the Keck School of Medicine of USC, other health-related USC entities and L.A. city and county officials to spearhead a massive, multidisciplinary COVID-19 response that went far beyond Dodger Stadium — establishing mobile clinics, making door-to-door visits, busing patients to vaccination centers and hiring community vaccine facilitators.

The collaborative effort highlighted the university’s role in building local connections and championing the health and well-being of its adjacent communities. “Everyone stepped up,” says Vassilios Papadopoulos, dean of USC Mann.

“Everyone shared the same mission of getting the vaccines out into the community.” Richard Dang, an assistant professor of clinical pharmacy and assistant director of the residency programs at USC Mann, helped lead mass vaccination efforts throughout the city. “At the time, USC was recognized as the institution providing this moment of hope,” Dang says.

Despite the unprecedented scale of the pandemic, Dang adds that USC Mann is accustomed to being a good neighbor to local communities, frequently organizing free health education and screening programs. “We also provide free access to tests for diabetes, high cholesterol, and high blood pressure, and distribute Naloxone for opioid overdoses,” he says.

After all, the good health of its neighbors is an essential metric of success for USC’s health sciences schools and its medical enterprise (which includes Keck Medicine of USC’s four hospitals and more than 100 clinics).

The university’s constellation of health sciences schools demonstrates just how far that health extends beyond the hospitals: They include the USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences; the USC Mrs. T.H. Chan Division of Occupational Science and Occupational Therapy; the USC Division of Biokinesiology and Physical Therapy; the Herman Ostrow School of Dentistry of USC; the Keck School of Medicine of USC; the USC Leonard Davis School of Gerontology; and the USC Suzanne Dworak-Peck School of Social Work.

Trojans as good neighbors

USC’s community-based work includes a consortium of scientists, researchers and clinicians committed to tackling health disparities and making a visible, positive impact on the neighborhoods surrounding the University Park and Health Sciences campuses by providing access to high-quality medical and social services.

“We’re always thinking about how we can bring all our expertise and work with the community to improve the health of our neighbors,” says Rodney B. Hanners, CEO of Keck Medicine of USC, the university’s health system.

At Ostrow School, oral health initiatives combine dental care with social services. At the Keck School of Medicine, a street medicine program seeks to reach the county’s unhoused population. USC Leonard Davis faculty and graduate students use advocacy and research to illuminate the gaping holes in our social safety net for elder care.

This ongoing relationship with local communities is mutually beneficial: Patients receive highly specialized care from the academic health system and have the opportunity to engage with health science practitioners through research, clinical trials and more.

Community members that choose to participate in USC studies contribute to more comprehensive and applicable insights that researchers and clinicians can use to inform patient care and drive innovation. Varied in their ethnicity, housing status, complexity of disease and other metrics, their participation leads to a better understanding of all communities. This kind of translational research has the power to transform basic discoveries into treatment directly beneficial to patients suffering from complex diseases such as Alzheimer’s disease or cancer.

Prioritizing access to care

While innovation and evidence-based care form two pillars of USC’s community-oriented health care philosophy, accessibility is an important third pillar.

The most significant driver of health disparities is access to health care,” says Raffi Svadjian, PharmD/MBA ’03, assistant professor of clinical pharmacy at USC Mann.

Since 2017, Svadjian has served as USC’s executive director of community pharmacies, supervising the three pharmacies operated by USC Mann: one on the University Park Campus, one on the Health Sciences Campus and one next to USC Verdugo Hills Hospital.

The school-operated pharmacies are an essential resource for both the USC community and those living around the university’s campuses and health facilities who would otherwise have few points of access to health care. Svadjian and his colleagues at USC Mann emphasize the power that pharmacists have to address health care access issues in under-resourced populations as first-line health care providers who are essential fixtures in communities.

Bringing the pharmacy to the community

The issue of access also informs USC Mann’s decision-making and civic engagement. In 2017, Papadopoulos approached Svadjian about opening a new pharmacy in South Los Angeles after pharmacy alumni highlighted the significant need in the area. Svadjian and his team surveyed more than 10 potential sites, guided by research from colleague Dima M. Qato, assistant professor of clinical pharmacy and spatial sciences and a leading researcher in pharmacy access. Qato most recently developed an interactive tool to map “pharmacy deserts” and determined that 25% of neighborhoods lack reliable access to pharmacies.

The team settled on a location next to where a Rite Aid had recently closed. Svadjian says the South L.A. pharmacy — which aims to open next year — represents a long-term commitment to the community, going beyond shorter engagements such as health fairs and workshops.

He hopes the new pharmacy’s impact will extend beyond dispensing prescriptions: His goal is to increase health education in the community while also providing an avenue for USC Mann students to learn from and interact with their neighbors.

“Obviously, one pharmacy is not going to change the world, but we have to start somewhere,” Svadjian says. He explains that by establishing a new pharmacy in a community that large corporations such as Rite Aid and CVS have avoided or left, the project furthers the university’s efforts to be a “good neighbor” to the communities surrounding its campuses and health facilities.

Letting the community fuel the research

Lourdes Baezconde-Garbanati, a Distinguished Professor of Population and Public Health Science at the Keck School of Medicine, also believes that addressing access to care is key when tackling health disparities.

Her collaborative approach to community health closely aligns with USC President Carol Folt’s Health Sciences 3.0 “moonshot”: She leads teams on community engagement within the USC Norris Comprehensive Cancer Center, the Southern California Center for Latino Health, the Center for Health Equity in the Americas, the Department of Population and Public Health Sciences, and other health institutes in Southern California to efficiently translate academic research into health care treatments, public health practice and policy. She also works with more than 100 USC faculty and over 190 community partners to transform community research into solutions that address the entire spectrum of disease prevention.

“It typically takes eight to 10 years for scientific discoveries and advances in medicine to make it out into the community,” says Baezconde-Garbanati, “but we’re really trying to accelerate that so people can live longer and healthier lives.”

She also works with the All of Us research initiative via the National Alliance for Hispanic Health to encourage community participation in research and clinical trials. She argues that in the age of artificial intelligence in health care, it is “especially urgent” for the needs and data of traditionally underrepresented communities to be reflected in emerging databases.

“USC is an anchoring institution in community health care, and we’re developing various ways to further engage with our neighbors so we can develop great innovation and amazing discoveries together with our community partners,” Baezconde-Garbanati says. “I feel like it’s a renaissance moment at USC, and I’m very proud to be part of that.”

Inclusion as a strength

In an effort to build a more equitable, culturally competent and compassionate health care system, the Keck School of Medicine also partners with the USC Dornsife College of Letters, Arts and Sciences for a master’s program in narrative medicine that brings health professionals into local communities to better understand the importance of storytelling for individuals, community wellness and the health care system.

One of only two such programs in the country, students in the program — often from the creative writing or medical fields — have workshop opportunities to teach and learn from community partners in topics such as strategies for challenging the hierarchy between patient and clinician.

This year, Keck Medicine of USC hospitals and USC Student Health earned an LGBTQ+ Healthcare Equality Leader designation from the Human Rights Campaign Foundation’s 2024 Healthcare Equality Index (HEI) survey. The survey found that Keck Medicine of USC — which is earning the distinction for the seventh time in recent years and includes Keck Hospital of USC, the USC Norris Comprehensive Cancer Center, and community hospitals USC Verdugo Hills Hospital and USC Arcadia Hospital — deserved a top score due to its health care facility policies and practices that are dedicated to the equitable treatment and inclusion of LGBTQ+ patients, visitors and employees.

The USC Gender-Affirming Care Program embodies this commitment by featuring a centralized program with specialists and staff who tailor comprehensive health care to transgender, nonbinary and gender-diverse patients.

This includes individualizing patients’ health needs based on their personal goals, which could include hormone therapies and surgical interventions, but also routine care such as preventative medicine and mental health care.

Program leaders developed early partnerships with community organizations such as The TransLatin@ Coalition, one of the largest trans-led nonprofit organizations in the country, to ensure that community members have a say in solidifying the program’s vision. USC clinicians and staff also host regular bilingual focus groups both at USC facilities and at The TransLatin@ Coalition’s headquarters in Koreatown to continue to promote mutual listening between the health system and the community.

Meeting people where they’re at

The COVID-19 pandemic revealed that sometimes, health care workers have to serve their communities even when face-to-face interaction isn’t possible.

Prior to the pandemic, the USC Suzanne Dworak-Peck School of Social Work’s telebehavioral health program was fairly small, with graduate students providing online mental health counseling to a mostly migrant worker population through a contract with Monterey County. Students also provided some pro bono services to local residents in L.A.

When the COVID-19 pandemic hit, the school was able to pivot and rapidly expand its online services and provide remote practicum opportunities for its graduate students who could no longer practice in person.

“There was this huge mental health need, with people dealing with the stresses related to COVID-19, such as grief and health issues,” says Professor Ruth Supranovich, associate dean of community and clinical programs at the school. “We were able to respond both to the need for the students, but also to the need in the community.”

Since that initial expansion, the program has partnered with CALHOPE, a crisis counseling assistance and training program that receives funding from the Federal Emergency Management Agency (FEMA) and is run by the California Department of Health Care Services to provide crisis support and counseling to the entire state. Through CALHOPE@USC, USC’s Telebehavioral Health Clinic — which opened in 2012 — provides inclusive individual and group counseling to anyone age 12 and older who lives in California. Services are free to the public and designed to be short term — the limit is six sessions per person.

Beyond short-term counseling, the clinic also connects community members to longer-range resources such as food assistance, mental health services, housing assistance and other forms of support.

The school also applied for and received funding from the California Victims Compensation Board to open a trauma recovery center for victims of violent crime. With the funding, USC therapists — including many graduate students and graduates of the master’s in social work program — provide evidence-based mental health treatment for trauma along with case management.

In addition to referrals from nonprofits, legal offices and word of mouth, the program receives client referrals from Keck Medicine of USC, USC’s occupational and physical therapy programs, the USC Department of Public Safety, and L.A. General Medical Center’s Hospital Violence Intervention and Prevention program.

With Trojans of all disciplines engaging in community-based initiatives and research, the university is well-poised to help Angelenos live longer, healthier lives.

“The stars are aligned — from the president’s office to our deans and faculty and to our students — in embracing our communities so its members can lead healthier lives,” Baezconde-Garbanati says. “There’s so much that we still need to do, and it really is going to take all of us coming together.”

This spring, scientists from the Keck School of Medicine of USC opened a new window into understanding the brain — literally.

Thirty-nine-year-old Jared Hager had injured his brain in a skateboarding accident. During emergency surgery, half of Hager’s skull was removed to relieve pressure on his brain, leaving part of the organ covered only with skin and connective tissue. A team at the Keck Medical Center of USC reconstructed his skull using a custom prosthesis that contained a transparent window.

The window, designed in collaboration with colleagues at California Institute of Technology, allowed the researchers to evaluate Hager’s brain function in a remarkable new way. While Hager played video games and strummed a guitar, the research team collected high-resolution brain data using functional ultrasound imaging. This type of imaging reveals brain changes that occur when a patient is performing a task — information that can be critical for assessing and treating traumatic brain injury.

“Functional ultrasound imaging can’t be done through the skull or a traditional prosthesis,” says Charles Liu, a professor of clinical neurological surgery, urology and surgery at the Keck School of Medicine and director of the USC Neurorestoration Center, who led the research team. “This is the first time physicians have been able to do it noninvasively in an awake patient through a window. The window allows us to monitor brain function and guide treatment in ways that were not possible before,” he says.

Effective treatment options for brain injuries and diseases have long been elusive. That’s in part because the brain — the command center of thinking, sensing, movement and emotion — is so complex to understand. The brain is also challenging to observe and study, especially in living humans.

Liu’s team at the USC Neurorestoration Center, which specializes in developing novel strategies to restore neurological function in those with injured or diseased nervous systems, is one of the many research groups at USC working to address the formidable challenges presented by brain diseases, from traumatic brain injuries and epilepsy to Alzheimer’s disease and other forms of dementia. Using advanced technologies and methodologies, they’re finding revolutionary ways to bring new clarity to the mysteries of our gray matter.

MAPPING THE BRAIN

Alzheimer’s disease is one of the most enigmatic brain afflictions and among the greatest health care challenges facing the nation. It affects nearly 7 million Americans — a number expected to double by 2060 — and there’s no known cure.

The disease is characterized by two hallmark changes in the brain: plaques made of a protein called beta-amyloid and tangles made of a protein called tau. Scientists have yet to discover what causes these proteins to accumulate. Some have speculated that dysfunction in the blood-brain barrier (a membrane that keeps harmful substances in the blood from reaching the brain) and inflammation of the brain’s blood vessels may set the stage for protein buildup.

Arthur Toga — Provost Professor of ophthalmology, neurology, psychiatry and the behavioral sciences, radiology and engineering and the Ghada Irani Chair in Neuroscience at the Keck School of Medicine — has developed cutting-edge imaging techniques that offer new insight into these parts of the brain.

At the Laboratory of Neuro Imaging (LONI) in the USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Toga and his research team program the radio frequency pulses used in magnetic resonance imaging (MRI) to observe the blood-brain barrier and the fluid-filled spaces around the brain’s blood vessels.

“These innovative techniques are really improving our ability to look at the most minute features of brain organization and brain function that may be affected by this disease process,” Toga says.

As Toga’s team works to create the most detailed neurological maps in existence, they’re also adding to LONI’s Image and Data Archive, a tool developed by Toga and his collaborators to facilitate real-time data sharing among thousands of researchers worldwide. Toga believes that such cross-institutional collaboration is essential for solving the riddle of Alzheimer’s.

He is one of the principal investigators on the Health and Aging Brain Study – Health Disparities (HABS-HD), a joint effort among five institutions to address the lack of diversity in Alzheimer’s disease research. Hispanic and African American populations experience a significantly greater risk of developing Alzheimer’s disease than non-Hispanic whites, yet much of what is known about the disease is based on data gathered among the latter group. HABS-HD has enrolled thousands of participants from underrepresented groups and is generating the world’s largest repository of data describing these populations.

“The path to discovery is paved with data,” Toga says.

PREVENTION IN PILL FORM

Thanks in part to the Image and Data Archive, the first drug to slow progression of Alzheimer’s disease — lecanemab — came on the market last year.

Pharmaceutical companies used data from the archive to develop the drug and design clinical trials. Those trials have shown that lecanemab, which targets and removes abnormal beta-amyloid deposits in the brain, slows down declines in memory and thinking by about 30% in those with early-stage Alzheimer’s.

For Paul Aisen, professor of neurology at the Keck School of Medicine and the founding director of the Alzheimer’s Therapeutic Research Institute, 30% improvement is not enough. “We’re very focused on research to find the best drugs to do better,” says Aisen, who leads research into evaluating drugs to treat — and even prevent — the disease’s underlying pathology in the brain.

Lecanemab is approved for people who have a confirmed diagnosis of Alzheimer’s disease in its mildest symptomatic stages. Aisen’s team is investigating the drug’s potential use in those whose brains are beginning to show Alzheimer’s changes but do not yet have any symptoms. “We believe if we remove the beta-amyloid as it’s starting to accumulate, while the brain is still functioning normally, we’re going to have an impact that is much better than a 30% slowing of disease progression,” Aisen says.

Another of the institute’s projects focuses on using lecanemab in conjunction with drugs that target brain tangles made of tau. By targeting both tau and beta-amyloid deposits at once, Aisen’s team aims to put the brakes on the disease even more effectively.

Aisen believes that within a decade, such pharmaceutical advances may make Alzheimer’s disease a thing of the past. He sees a future where clinicians will monitor everyone starting in middle age, identifying those who are at risk for the disease and prescribing drugs that can keep proteins from accumulating abnormally in the brain.

“It will be like checking your cholesterol and treating high levels in midlife so that you don’t get heart attacks and strokes in later life,” he says. “We think we can prevent Alzheimer’s disease the way statins [drugs that lower cholesterol] have dramatically lowered the occurrence of heart attacks.”

BESPOKE BRAIN FITNESS

While Aisen envisions routine Alzheimer’s prevention for all, researchers at the USC Center for Personalized Brain Health at the Keck School of Medicine are focusing their prevention efforts on a subset of people who are known to have a high risk of developing the disease: those who are carriers of a fairly common genetic variant called APOE ε4.

Roughly one in four people carry one copy of the gene, elevating their risk of Alzheimer’s. Those who have two copies of the gene — 2% to 3% of the population — face eight to 12 times the risk for the disease.

“When people take a genetic test and find out they have the APOE ε4 gene, they are often scared and unsure of what to do — especially if they have a family member who already has dementia,” says Hussein Yassine, professor of neurology and gerontology at the Keck School of Medicine and director of the center. “We’re trying to fill this gap by providing resources to help patients do what they can to prevent the disease.”

The center has two components that inform one another: a clinic that develops personalized diet and exercise interventions for each patient to potentially slow cognitive decline, and a research wing focused on the development of new drugs. “This bridge between research and the clinic is quite novel,” Yassine says.

One example of the center’s translational approach is a multi-pronged investigation into the role of omega-3 fatty acids, which are found in foods like salmon and walnuts, in the brain health of APOE ε4 carriers. Imaging studies have shown that the brains of APOE ε4 carriers are deficient in omega-3s years before Alzheimer’s brain changes set in. Yassine launched a clinical trial to test whether early omega-3 supplementation in people with APOE ε4 can slow down disease progression. He also partnered with Kai Chen, professor of research radiology at the Keck School of Medicine, to invent a new imaging technique that traces omega-3s in the brain.

AI SEE YOU

High-resolution imaging techniques like those used by Liu, Toga and Yassine help researchers visualize the intricacies of brain tissue in never-before-seen ways. Yet the human eye itself has limitations that affect how brain images are interpreted. Andrei Irimia, associate professor of gerontology at the USC Leonard Davis School of Gerontology, is using artificial intelligence to push past those limits.

Irimia and his colleagues use an AI technology called deep neural networks to analyze MRI brain scans. The AI model allows Irimia’s team to identify subtle patterns in the brain scans that the human eye might not be able to detect.

One application of the technology is assessing biological brain age, an important factor in the development of Alzheimer’s disease and other forms of dementia. While the risk of developing these neurodegenerative diseases increases with age, not everyone’s brain ages at the same rate. “A person who is very fit and has a healthy lifestyle might experience low and relatively much slower rates of atrophy in the brain compared to more sedentary individuals,” Irimia explains.

He notes that traditional measures of brain aging, which include judging brain age by the thinning of the cerebral cortex, may not offer the fullest picture.

“By identifying patterns in a very large array of changes pertaining to brain anatomy, these deep neural networks can estimate brain age a lot better than we could based on measures that have been identified by humans,” Irimia says.

THE BRAIN ELECTRIC

At the Keck Medical Center of USC, where Liu and his colleagues implanted the transparent skull prosthetic, digital technologies are being integrated into the brain itself to help restore function in those with brain and spinal cord injuries.

In collaboration with colleagues at Caltech and the University of California, Irvine, Liu’s team is developing brain-computer interfaces to help paraplegic patients regain feeling in their legs and walk again. These interfaces offer a bidirectional communication link between the brain’s electrical signals and a bionic bodysuit (aka “robot exoskeleton”) worn by patients that can aid in movement.

Patients control the movement of the exoskeleton with their thoughts. Electrodes implanted in the brain record electrical impulses that orchestrate movement, which are then translated into commands that control the robotic suit. Not only do patients move, they can feel the motion. “When the robot exoskeleton moves, patients feel every step because key areas of the brain are stimulated,” Liu says.

Implantable brain devices are also being used for epilepsy treatment at the center. Responsive neurostimulation (RNS) implants monitor waves in parts of the brain where seizures begin, detect unusual electrical activity that can lead to a seizure and, within milliseconds, deliver small bursts of electrical stimulation to “stop the seizure in its tracks,” says Christianne Heck, professor of clinical neurology at the Keck School of Medicine, medical director of the USC Comprehensive Epilepsy Program and co-director of the USC Neurorestoration Center.

Keck Medical Center was the world’s first medical center to implant the FDA-approved RNS device in an epilepsy patient, setting an important precedent for the approval of all brain computer technologies worldwide. After nearly two decades of researching RNS, Heck believes these responsive brain devices hold promise for treating other neurological conditions such as stroke and for advancing neuroscience as a whole.

“RNS is a great window to what’s going on in the brain and has great potential for us to understand basic questions about how complex the interconnections are from one part of the brain to another,” Heck says.

Whether the windows that USC researchers are opening are literal or figurative, they’re not just illuminating the brain’s inner workings — they’re defining the next frontier of brain science.

In April 2022, USC President Carol Folt gave her first in-person State of the University address at Bovard Auditorium. After two years of pandemic uncertainty, the USC community was ready to come together and hear Folt’s agenda for what lay ahead.

“With our unrivaled size, scale, breadth and excellence, we can become national leaders in access and belonging, in sustainability and in partnering with communities for health, safety, freedom and prosperity,” Folt said.

She went on to articulate her vision for establishing USC as the international standard-bearer for collaborative learning and discovery through what she dubbed “moonshots” — one of which was a major expansion of the university’s health sciences efforts.

“No other university has this constellation of resources and schools to create a healthier society for the future,” she added.

It was a clarion call. Folt, who declares USC to be the “school of schools,” added that with Trojans working across disciplines to drive innovation in health care, “the potential is limitless.”

Her ambitious plan has resonated throughout the faculty: “USC is exactly the place for an initiative like President Folt’s health care moonshot,” says Mark S. Humayun, University Professor of ophthalmology and biomedical engineering at the Keck School of Medicine of USC. “We can leverage the expertise of USC’s unique cross-disciplinary minds to really tackle the health care issues of today and into the future.”

Collaborate and create

Folt’s announcement marked an important first step in supercharg-ing collaboration within USC’s five health schools and its academic medical system, Keck Medicine of USC. The initiative, dubbed the Health Sciences 3.0 moonshot, aims to catalyze team-based research and education to develop new models of care for the communities surrounding USC’s campuses. The moonshot will take advantage of the AI revolution and collaborative care to overcome the greatest challenge of health care — providing improved outcomes at an affordable price.

Even before the initiative’s announcement, Folt was already in motion, creating the Office of Health Affairs to facilitate cross-disciplinary and cross-school collaboration. In May 2021, she hired physician-scientist Steven Shapiro to lead that office as the first senior vice president for health affairs.

Shapiro previously served as president of University of Pittsburgh Medical Center health services, the largest academic health system in the United States. His mission at USC: to create an infrastructure to help the university’s health entities — which represent 65% of the university’s total research, 70% of total full-time faculty and 54% of full-time staff — work with each other and the university as a whole to develop these new models of care.

“We are also on the verge of understanding the molecular basis of disease with the opportunity to cure diseases that have plagued the world for centuries,” Shapiro says. “Indeed, we are about to enter another golden age of medicine.”

In addition to building interdepartmental partnerships around artificial intelligence, digital health and health technology, the office also creates incentives for this work, such as the Nemirovsky Engineering and Medicine Opportunity Prize, which supports early-stage research at the intersection of health sciences and engineering.

The university’s health enterprise includes four hospitals — Keck Hospital of USC, USC Norris Cancer Hospital, USC Verdugo Hills Hospital and USC Arcadia Hospital — more than 900 faculty physicians, and more than 100 unique clinics in Southern and Central California and Las Vegas.

“We are realizing the future of medicine with research-based inputs combined with AI, brilliant minds and compassionate care-givers to deliver tomorrow’s medicine today,” Shapiro says.

A pioneer from the beginning

Ever since USC founded the region’s first medical school in 1885, the university has been a critical part of providing health care to the Los Angeles community, particularly its most vulnerable patients. Beyond training physicians in the newest, most advanced clinical interventions available, USC has pioneered new treatments for some of the most complex diseases.

Today, the USC Health Affairs office comprises the USC Suzanne Dworak-Peck School of Social Work, the Herman Ostrow School of Dentistry of USC, the USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, the USC Mrs. T.H. Chan Division of Occupational Science and Occupational Therapy, the USC Division of Biokinesiology and Physical Therapy, the USC Leonard Davis School of Gerontology, the Keck School of Medicine of USC, and the USC health system — Keck Medicine of USC.

Faculty from other schools, including the USC Dornsife College of Letters, Arts and Sciences, USC Price School of Public Policy, and the USC Viterbi School of Engineering, are intrinsically involved in research, education and programs that address the pressing health needs of our time.

The ‘school of schools’

While Trojans across schools have long collaborated, there was a limit to what researchers, scientists and clinicians could achieve within individual disciplines to spur discoveries that help patients live longer, healthier lives.

“The United States has been criticized for both the high cost of care and outcomes such as life expectancy, which have lagged behind our peer nations,” Shapiro says. In reality, he adds, only a small fraction of this cost is directly related to health care.

He points out that despite health issues such as homicide, suicide, drug addiction, and behaviors such as diet, exercise, sleep, smoking and significant health inequity, “There is no better place than the United States to care for the most complex acute health problems.”

Every school at USC, he says, is playing a role to improve health for all. “Never before have our physicians and scientists worked so closely together,” Shapiro says. “At USC, we are tackling the many factors to lead a life well-lived.”

In June 2023, for the first time, USC’s annual research expenditures surpassed $1 billion, including USC in an exclusive group of just 13 private universities in the country that can boast the same. A nationally recognized measure of a university’s innovation potential, the $1 billion included significant investments in Folt’s moonshots in computing, sustainability and health.

That huge number represents the breadth of research that Trojans are engaged in — from oncology to the onset of aging, to cardiac care, to AI in health care — all to tackle humanity’s biggest problems.

Ishwar K. Puri, senior vice president of the USC Office of Research and Innovation, calls USC’s interdisciplinary work in the health space the “backbone” of the entire university. “It allows us to leverage the strength of the university both within the health sciences schools and outside the health sciences schools,” Puri says.

For example, at the USC Institute for Addiction Science, faculty members across disciplines produce innovative and adapt-able scientific evidence and educational programming to increase awareness, correct misperceptions, counteract stigma and inform policy on addiction. The institute is a partnership between the USC Suzanne Dworak-Peck School of Social Work, Keck School of Medicine of USC, and USC Mann School of Pharmacy and Pharmaceutical Sciences.

Another exciting example of an interdisciplinary feat involves the USC Information Sciences Institute — led by University Professor Shri Narayanan of USC Viterbi and involving other researchers from USC Viterbi, USC Dornsife, the Keck School of Medicine and the University of California, Los Angeles — where researchers are attempting to predict psychological health risk factors to support clinical screenings for issues such as depression and suicidal ideation.

In line with Folt’s vision of the university as an international standard-bearer for collaborative learning and discovery, USC researchers such as Arthur Toga and Paul M. Thompson at the Keck School of Medicine and the USC Mark and Mary Stevens Neuroimaging and Informatics Institute are discovering new ways to use neuroscience, mathematics, computer science and software engineering for brain research.

Likewise, University Professor Peter Kuhn of USC Dornsife works with experts in machine learning and artificial intelligence from USC Viterbi to analyze thousands of blood sample images from “liquid biopsies” to work toward better outcomes in cancer therapies. The minimally invasive alternative to tissue biopsies aids physicians in detecting and managing early- and late-stage cancers.

Diversity spurs new models of care

At almost 10 million people, Los Angeles County’s population is larger than that of 40 states and extremely diverse. Residents include people from more than 140 countries who speak a combined total of more than 200 languages. There is no ethnic majority, and more than one-third of residents are born outside the United States.

It’s a microcosm of the world — and what ails it.

Serving the communities around USC drives innovation, says Rodney B. Hanners, CEO of Keck Medicine of USC and president and CEO of the USC Health System.

“L.A.’s diverse population provides a rich foundation for science and research in tailoring leading-edge treatment and care to individual needs, whether it’s based on race, gender or other demographics,” Hanners says.

For example, roughly 60% of cancer patients in clinical trials at the USC Norris Comprehensive Cancer Center are from historically underrepresented populations. The center works with community organizations to connect patients who want to participate in clinical trials, which contributes to a wealth of varied perspectives and to closing the gap on health equity.

Meeting patients where they are

The Office of Health Affairs is also working to transform health care by delivering exceptional team-based care, not just in a hospital setting, but increasingly in patients’ homes, in the community and in the streets.

One example is new research led by Keck Medicine of USC medical oncologist Jorge Nieva. In his work, Nieva is exploring the benefits patients experience when receiving cancer care at home combined with telemedicine appointments and remote monitoring. He is leading the first clinical trial to test at-home administration of immunotherapy in the treatment of non-small cell lung cancer, which could lay the foundation for the future of at-home cancer care.

Since the inception of the Keck School of Medicine of USC 140 years ago, USC has also collaborated with Los Angeles General Medical Center to provide the equitable and leading-edge care of its academic health center to surrounding communities.

USC patients have the highest case mix index (CMI) nation-wide for acute care hospitals, partly because many other hospitals transfer their patients to Keck Hospital to care for cases too com-plex for them to handle. CMI is a metric that reflects the heterogeneity of the patients treated at the hospital and the complexity and severity of their cases.

In other examples, for the past 50 years, the Ostrow School has combined dental care with social services to address the oral health needs of L.A. communities holistically through mobile dental clinics, health fairs, screenings and educational programs.

Outside the U.S. military, the school boasts the world’s largest fleet of mobile clinics, which provides treatment to school-age children across Southern California. The school also operates stationary clinics where Angelenos need it the most, such as the Union Rescue Mission in downtown L.A.’s Skid Row.

Likewise, each year, students from the USC Suzanne Dworak-Peck School of Social Work contribute nearly 1 million hours of service to communities through internships. Students from USC Leonard Davis and USC’s occupational and physical therapy pro-grams, among other programs from the health sciences schools, have also devoted their internship practicums to serving the needs of L.A.’s diverse communities for decades.

The university also boasts the largest street medicine program in the country. In addition to medical clinicians, the program’s inter-disciplinary team brings together professionals from many of the health sciences schools, including dentists, occupational therapists, social workers and other experts dedicated to meeting unhoused Angelenos where they are.

And USC continues its long-standing relationship with Children’s Hospital Los Angeles (CHLA), through which USC physicians care for some of the most medically complex pediatric patients.

Building a culture of innovation

These programs illustrate one of USC’s biggest strengths: its approach to innovation. Puri says, “We move from discovery to life-saving therapy for patients.”

USC entities such as the Alfred E. Mann Institute for Biomedical Engineering and the Stevens Center for Innovation encourage entrepreneurship among researchers and practitioners by providing an avenue to commercialize discoveries such as at-home testing kits for lithium toxicity or stretchable microneedles.

The Keck School of Medicine of USC also has one of the nation’s highest rates of funding per investigator from the National Institutes of Health, highlighting the school’s prowess in advancing medical knowledge and funding novel discoveries. According to Shapiro, this means USC researchers are able to bring in more resources and have the wherewithal to form larger, multidimensional collaborative groups. This gives USC the agility to translate research into clinical therapies that benefit local and global communities.

“Our moonshots take advantage of this special time of computational AI-driven scientific progress,” Shapiro says. “We have an opportunity to understand and cure disease while delivering continuous, often digital, care to our patients wherever they are. This is how we will improve human health.”

 

A custom heart or vascular stent for everyone who needs one. Your own stem cells providing the material for 3D-printed organs. Spray-on skin. A powerful diagnostic partner that enables more equitable health care. This is the promise of artificial intelligence (AI), now a full member of any health care team — and USC is leading the way.

AI excels at analyzing large amounts of datasets, and it has applications across every aspect of health care. At USC, researchers and clinicians are using AI to minimize risks and improve patient outcomes, create precision surgical techniques, hasten drug discovery and interpret medical images with impressive accuracy — all treatments thought out of reach just a few years ago.

“In 1980, medical knowledge doubled every seven years,” says Summer Decker, founding director of USC’s Center for Innovation in Medical Visualization. “Today, it more than doubles every 72 days. AI enables us to track patterns we couldn’t see before, because it would be almost impossible to analyze that volume of data. It will help us start seeing those patterns earlier so we can begin addressing problems earlier.”

Already, AI-powered wearables monitor patients’ health metrics 24/7, while 3D printing produces replicas of human organs for study in various applications such as transplantation, disease modeling and drug testing. “This isn’t science fiction,” says Inderbir Gill, executive director of Keck Medicine’s USC Urology, who himself regularly performs AI-assisted robotic surgery. “How can you not be impressed by the potential of AI? It’s coming at us at breakneck speed.” Gill is also Distinguished Professor and chair of the Catherine and Joseph Aresty Department of Urology at the Keck School of Medicine of USC, which hosted the first AI West Med Symposium in February.

AI also helps solve a more mundane — and yet very real — health care challenge: physician burnout from administrative tasks. By using AI to update electronic health records, clinicians can free up time for patient care.

“The opportunity of AI is to take this massive amount of data and improve humanity,” says Steve Shapiro, USC’s senior vice president of health affairs. “By having all this incredible wealth of data and AI algorithms, we’re going to be able to ignite discovery.

“Once we have all this information, we can generate hypotheses, take that to the lab and make real discoveries,” Shapiro adds. “Our scientists, students, clinicians can ask the most important questions and challenge dogma.”

A strong partnership among Keck Medicine of USC, the university’s health schools and the USC Viterbi School of Engineering, alongside national and global colleagues, provides the ingredients for medicine that ultimately may help millions worldwide.

But will AI replace our doctors? Not at all, says Carolyn Meltzer, dean of the Keck School of Medicine. For all of AI’s capabilities, algorithms can’t do everything: Compassion, ethics and creative, nonlinear thinking remain strictly human. “It’s not that AI will replace the physician,” Meltzer says. “It’s that the physician who uses AI will replace the physician who does not use AI.”

Meet some of the physicians at USC who are deploying AI tools to transform healing.

From the Virtual to the Physical

Summer Decker, founding director of USC’s Center for Innovation in Medical Visualization and professor of Clinical Radiology, Surgery and Pathology, creates 3D-printed models of human anatomy — for surgical planning, teaching, medical device development and patient care. Leveraging AI, she says, can improve print quality, detect and correct errors before they happen and make 3D printing more accessible by simplifying the process.

“With 3D printing, we can reduce the time needed for surgery, minimize the risk to patients and know exactly what size surgical device or replacement part to use for each individual. It gives surgeons a road map inside the body with real-time 3D views of a patient’s anatomy. There’s so much we can do with 3D information, whether you’re a surgeon planning an operation or a student learning a procedure. Our patients are the ones who will benefit. When I looked at where I wanted to be to push this technology, the answer was USC because it’s a world leader.

“Our lab holds several patents on a technology that will seed a 3D print with demineralized bone matrix, which can form a custom internal scaffold for facial injuries in kids. Unlike a metal plate, the print and tissue will grow with them. In bioprinting, which is already here, you take a person’s stem cells and reprint their anatomy. Of course, certain organs are easier than others to print. The brain is a long way away — if ever. AI will give us the tools to be better at what we do. We’ve just got to drive it.”

Building Custom Stents

Sukgu Han is a vascular surgeon and biomedical engineer who designs and crafts custom stents for his patients. He is a professor of clinical and neurological surgery and chief of the Division of Vascular Surgery and Endovascular Therapy at Keck Medicine. He also serves as the co-director of the Comprehensive Aortic Center at Keck Hospital and program director of vascular surgery residency and fellowship at Keck School of Medicine.

“Everybody’s anatomy is a little different. An aneurysm — a bulging, weakened area in the aorta — can distort the anatomy as the blood vessel twists on itself. Having the ability to tailor each patient’s stent to fit their anatomy and protect the aorta can make surgery safer. I began making complex, custom aortic stent grafts for my patients 10 years ago. I’ve now done more than 500 — a lot of it I’ve done manually. The next phase will be automated AI analysis, which will speed the process of sizing the stents in three dimensions to fit each patient.

“We recently launched a project using an AI vessel-segmentation algorithm that will compare a patient’s CT scan with their previous scan to determine what is happening in their aorta in much greater detail than how we’re doing this currently — which is basically a radiologist or surgeon putting the images side by side and hoping to detect any changes that make a difference in the patient’s care, but can easily be missed due to human error.

“We haven’t even scratched the surface in tailoring each patient’s treatment to a deeper granularity. No one has the technology to 3D print some of these custom stents — yet. That may be coming our way sooner than expected. Next is printing cardiac structures like heart valves for implantation. Who knows what we’ll be talking about in five years?”

Preventing Avoidable Injuries

William Padula is an advocate for using AI to better predict pressure injuries, commonly known as bedsores. He is assistant professor of pharmaceutical and health economics at the USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences.

“More people die from pressure injuries acquired in the hospital than from car accidents. The annual cost of hospital-acquired pressure injuries in the United States is $30 billion and 60,000 deaths. By my calculation, we could probably prevent most injuries in a smart hospital infrastructure using data science for $10 billion to $15 billion and eliminate $30 billion in waste and save many lives. This would give us a lot of financial bandwidth to do other things, such as gene therapy for sickle cell disease or for kids with cystic fibrosis.

“In the 1980s, nurses began using a paper-based tool to document pressure injury risk factors on a scoring sheet — an antiquated method by today’s capabilities. USC is collaborating with Johns Hopkins University and UH Cleveland Medical Center; we developed a risk-assessment model using machine learning, which increased the accuracy of risk prediction to 74% — a more than 20% jump over human methods.

“An unbiased machine-learning tool based on data consistent across all patients — whether sensory data or blood tests — will enable us to better predict the risk each patient faces of developing a pressure injury or other adverse health outcomes. Through AI, we can make health care more equitable and more focused on prevention and treatment. That’s the potential of AI.”

Offering ‘An Extra Set of Eyes’

Melinda Chang, assistant professor of clinical ophthalmology at USC Roski Eye Institute, part of Keck Medicine of USC, wants to improve diagnosis of swollen optic nerves in kids, a potentially serious neurologic problem. She believes AI can reduce the need for diagnostic procedures that require sedation of children.

“Swollen optic nerves, known as papilledema, can be a sign of a brain tumor, hydrocephalus or meningitis. It’s one of the most common reasons kids are referred to our pediatric neuro-ophthalmology clinic. Complicating the diagnosis is pseudopapilledema, in which the optic nerves also appear swollen but are essentially benign.

“No single imaging technique can accurately differentiate between the two conditions on its own. Even combining them all might not be accurate enough. A full workup requires an invasive lumbar puncture and sedation in kids, which we want to avoid. We recently initiated a multicenter study comparing human diagnoses and an AI model programmed to scrutinize minute details in photos of the back of the eye.

“The human experts did very well in distinguishing severe papilledema from pseudopapilledema, but AI did much better. In cases of mild papilledema, which is harder to differentiate, AI achieved an accuracy of approximately 70% and sensitivity close to 90%, far surpassing the performance of human experts, whose accuracy ranged from 53% to 59% and sensitivity from 39% to 53%. For us, that means AI has promise in these difficult cases in potentially reducing the rate of kids undergoing unnecessary tests and missed neurological problems. AI won’t replace doctors but will serve as an extra set of eyes.”

Cancer Care at Home

Jorge Nieva is exploring at-home care for patients with non-small cell lung cancer, which is made possible by telemedicine and remote monitoring. A Keck Medicine of USC medical oncologist and lung cancer expert, he is associate professor of clinical medicine, Keck School of Medicine of USC.

“These days, 30% to 40% of my lung cancer patients can be treated with a pill. Some cancers, like non-small cell lung cancer, still require injections. Our new clinical trial deploys nurses to patients’ homes to administer immunotherapy medication under the skin. During the pandemic, the use of telemedicine exploded, and patients appreciated the convenience, especially in Los Angeles, which can be hard and stressful to navigate. The trial also relies on telemedicine visits and remote monitoring. It’s like a modern house call. My excitement about digital tools like these is having access to real-time and self-reported data on the patient’s vital signs, movement data and symptom management. It leads to better decision-making.

“Some applications of AI in health care will be very important, such as assistance with the analysis of medical images and pathology slides, and chatbots for triaging patient communications. When seeking to improve the health of a population through better care coordination and patient engagement, AI can help ensure patients get timely cancer screenings and follow-up. But we’re not at the day yet when someone will type their symptoms into a box, receive a diagnosis and a prescription in the mail.

“With something as critical as a diagnosis, you’re always going to want a human who has thought about the problem enough that they’re willing to say, ‘No, I’m responsible. The buck stops with me.’”

From Skin-Like Wearables to Gut Clues

Yasser Khan invents AI-powered wearable, implantable and ingestible medical devices. He is an assistant professor of electrical and computer engineering at the USC Viterbi School of Engineering and the USC Institute for Technology and Medical Systems Innovation, a joint Keck School of Medicine of USC-USC Viterbi initiative.

“Imagine using AI-enabled devices to track your physical and mental health. By printing electronics on plastic and rubber, wearables become so thin, flexible and stretchable, they behave like a second skin. One study I was involved in developed a ‘bandage’ that can measure tumor growth within the width of one human hair. Now we’re designing a wearable sensor in patch form with physiological and bio-chemical sensing capability to help classify mental states. And the skin-like electronics revolution is just starting.

“In addition, my lab is focused on implantables and ingestibles — the latter is brand-new work out of USC. We are now designing a combination wearable/ingestible system that could someday serve as a ‘Fitbit for the gut’ for early disease detection. It combines a smart pill that can measure gases, chemical markers and neurotransmitters, plus a wearable system (essentially a coil over your shirt) with high resolution to follow the capsule. There’s no way now to measure these things noninvasively. The hope is this capsule someday can carry a chemotherapy drug and be released in the exact location to target the cancer.”

Hope for Diabetics

David G. Armstrong is a professor of surgery and neurological surgery at the Keck School of Medicine of USC, a podiatric surgeon and limb preservation specialist with Keck Medicine of USC. A diabetic wound care expert, he works within a coordinated program to treat diabetic foot ulcers and other chronic wounds. Their work is merged with technologies such as injectable sensors, gene-therapy- directed wound healing and Bluetooth-enabled artificial blood vessels.

“Every second someone develops a diabetic foot ulcer. Half of these people get a foot infection, and 20% end up in the hospital. Every 20 seconds there’s an amputation. We believe virtually all of this is preventable. That’s why we developed the predictive Smart Boot, a wearable technology supported by AI-based algorithms that can help diabetic patients recover from dangerous foot wounds. It can identify not only whether people are wearing it but how fast they move, the steps they take, if they’re unsteady or about to fall.

“Right now, there’s a fundamental blurring of the lines between consumer electronics and medical devices. With our Caltech colleagues, we’re bringing smart bandages that sense and respond to inflammation or infection to clinical use. Having worked with augmented/virtual reality for two decades, I’m also excited about the Apple Vision Pro opening up possibilities for surgical procedures, medical training and care.

“These devices capture the imagination — and they’re getting better at helping us look after our patients better and drive medicine forward. By marrying our humanity with the technology, we can effect positive change on ourselves and the planet. We don’t have to predict the future. It’s all happening now.”

Anyone who’s healed from a cut or a scrape has witnessed the incredible regenerative power of stem cells. These cells can create identical copies of themselves, creating new cells and tissues that replace damaged ones.

Stem cells are active in some areas of our body throughout our lives, like the skin and blood. But in many critical organs, including the heart and kidneys, stem cells are absent. When such tissues are damaged due to aging, injury or disease, they don’t regenerate, leading to devastating health consequences.

USC researchers are at the forefront of an emerging field called “clinical regenerative medicine,” which taps stem cells’ restorative powers to tackle some of the hardest-to-treat diseases, ranging from heart failure to blindness.

“We now have the ability through stem cells to generate replacement cells that we can use as therapeutics to rebuild the human body,” says Charles (Chuck) Murry, a renowned expert in regenerative heart medicine. In August, Murry joined Keck School of Medicine of USC as the new head of USC Stem Cell, chair of the department of stem cell biology and regenerative medicine, and director of The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research.

Launched in 2013, USC Stem Cell is a universitywide initiative that connects over 100 research and clinical faculty in multiple disciplines across USC and Children’s Hospital Los Angeles (CHLA) with the common goal of translating basic stem cell science into clinical therapies. It has matured over the past decade with support from the Eli and Edythe Broad Foundation as well as the California Institute for Regenerative Medicine (CIRM), a state organization created to accelerate stem cell research.

USC Stem Cell collaborators are employing stem cells to grow organ and tissue replacements, halt or reverse the progression of life-threatening diseases and create living models of human organs in the lab, providing novel platforms to screen for disease-fighting drugs.

“Clinical regenerative medicine is going to have an impact on par with antibiotics or vaccinations,” Murry says. “It’s going to be revolutionary.”

The stem cell projects currently underway across USC will transform treatments from our skull to our knee and many organs in between. As with the classic board game Operation, we’ve broken down a selection of these projects by body part — funny bone not included.

SKULL

The bones of our skull protect one of the most important human organs: the brain. When those bones are compromised either because of a congenital condition, injury or surgery, the defect may affect not only the appearance of the skull but also brain function itself. Since skull bones do not regenerate after infancy, surgery is often needed to repair defects.

Yang Chai, University Professor, interim dean and associate dean of research at the Herman Ostrow School of Dentistry of USC, treats craniofacial birth defects. His work inspired him to develop an innovative treatment option for patients with significant defects — essentially holes — in the calvarial bones at the top of the skull.

Typically, these holes are surgically closed with a metal or plastic plate. For pediatric patients, neither option is ideal because a synthetic plate will not grow in concert with the child’s developing brain. Many of these implants fail within 20 years.

Collaborating with Yong Chen, professor of aerospace and mechanical engineering and industrial and systems engineering at the USC Viterbi School of Engineering, Chai designed a “living” implant for skull bone regeneration. It’s a 3D-printed scaffold made of a mineral found in teeth and bones called hydroxyapatite. The scaffold can be customized to fit a patient’s defect precisely and seeded with a patient’s own bone marrow-derived stem cells.

In animal models, as the stem cells mature, they grow and integrate with the surrounding skull to cover the defect within about six months. The new bone becomes as strong as the native bone. Chai and his collaborators — including Mark Urata, professor of clinical surgery at the Keck School of Medicine of USC — are poised to begin clinical trials in humans.

“Ours is going to be a biological solution for a biological problem, instead of a mechanical solution [i.e., a synthetic plate] for a biological problem,” Chai says.

BRAIN

Studying human brain development is important in understanding how neurodevelopmental issues such as autism spectrum disorder arise and progress. But traditional research methods have proved insufficient for observing the human brain as it develops. Current brain imaging techniques don’t offer a resolution that is high enough to understand brain functionality at the cellular level. Postmortem human brains don’t provide a window into early growth, and animal models don’t possess the complexity of the human brain.

“The best way to access human brain development is really to take advantage of human stem cells,” says Giorgia Quadrato, assistant professor of stem cell biology and regenerative medicine at the Keck School of Medicine of USC.

Quadrato has pioneered a way to grow masses of brain cells in the lab from stem cells. Within six months, these cells mature into tiny structures (“brain organoids”) about two millimeters in diameter that contain all the various cell types of specific brain regions. The organoids allow Quadrato’s team to study the cells’ development in real time, model neurodevelopmental diseases and screen for potential new treatments.

One of her lab’s most noteworthy innovations is an organoid model of the cerebellum, a brain region that plays a role in movement, cognition and emotion. In certain neurodevelopmental and neurodegenerative disorders like autism spectrum disorder and cerebellar ataxia, cells in the cerebellum called Purkinje neurons degenerate. Quadrato’s team is the first to succeed in growing Purkinje cells with all the features of functional neurons in a human system.

While the cerebellum models were grown from healthy cells, Quadrato has also grown organoid models of the cortex — a brain region involved in cognitive function — derived from the cells of a patient with a disease-causing variant of the SYNGAP1 gene. This variant is one of the top risk factors for autism spectrum disorder. The lab’s organoid models shed new light on how the variant disrupts early development of the cortex.

 

EYES

As we age, changes to the retina, the delicate tissue at the back of our eyes, can lead to vision loss. Photoreceptor cells that sense light and send signals to the brain can deteriorate due to inflammation, genetics and lifestyle habits such as smoking. At the center of the retina, the macula, which controls straight-ahead vision, is particularly vulnerable to damage.

Age-related macular degeneration (AMD) is the leading cause of severe vision loss among people over 50 in Western countries. Because there’s no known way to regenerate photoreceptors, AMD has had no effective treatments — until now.

Mark Humayun, University Professor of ophthalmology at the Keck School of Medicine of USC and co-director of the USC Roski Eye Institute, and his collaborators are using stem cells as a gateway to restoring vision in people with dry AMD, the most common form.

The disease affects not only photoreceptor cells but also a vital group of cells that protect them from damage called retinal pigment epithelium (RPE) cells. Humayun and his team developed a tiny patch filled with RPE cells derived from stem cells that can be surgically implanted in the eye, where the young cells can shield patients’ photoreceptors from further degeneration.

Clinical trials of the patch are run by Regenerative Patch Technologies, the company he co-founded with Dennis Clegg and the late David Hinton. In the first phase of the trial, 27% of patients experienced improved vision.“We found that these young RPE cells are very robust,” Humayun says. “They survive much better than adult-aged RPE. Patients who improved are still keeping the same level of vision three years later.”

This fall, during the trial’s second phase, the patch will be tested in a larger number of dry AMD patients. Among them will be patients with less severe disease than patients in the first phase. Humayun expects that in this phase the patch will improve vision in even more patients and to a greater extent.

MOTOR NEURONS

Amyotrophic lateral sclerosis (ALS) — often called Lou Gehrig’s disease — is a devastating neurodegenerative disease with no known cure. It affects motor neurons, which are nerve cells in the brain and spinal cord that control voluntary muscle movement and breathing. Over time, as motor neurons degenerate, the brain can no longer command muscle movements, and people with ALS may lose their ability to speak, eat, walk and breathe.

Finding universally effective treatments has been difficult because the disease’s root causes are not fully understood. While having a family member with ALS increases your risk of developing it, most cases occur with no family history or clearly associated risk factors. “In these cases, we believe that multiple gene mutations come together in one person,” says Justin Ichida, an associate professor of stem cell biology and regenerative medicine at the Keck School of Medicine of USC whose research is centered on fighting the disease.

Stem-cell technology has provided Ichida an avenue for new leaps in discovery. He and his team reprogram adult skin or blood cells from an ALS patient into stem cells. These cells are then coaxed into developing into motor neurons that are genetically identical to the patient’s own motor neurons. The process has allowed Ichida’s lab to test thousands of compounds to see how the neurons respond.

One of Ichida’s most exciting discoveries is that inhibiting a protein called the PIKFYVE kinase improves the survival of motor neurons derived from patients with varying types of ALS. His startup company, AcuraStem, developed a druglike molecule to suppress this kinase and licensed it to a pharmaceutical company, which is now developing it into a drug for clinical trials. “This could be applicable for essentially all ALS patients, rather than just a subset that have a certain type of mutation,” Ichida says.

EARS

Inside your cochlea — the spiral structure inside your inner ear — a few thousand tiny sensory receptors with bundles of hairlike protrusions (so-called “hair cells”) perform a function essential for hearing. They convert the mechanical vibration evoked by sound waves into electrical signals that your brain interprets. When they’re damaged either from wear and tear or disease, hair cells can’t be normally replenished.

That’s true in humans, mice and other mammals. But in non-mammalian vertebrates, such as songbirds, damaged hair cells regenerate in a matter of weeks. The difference comes down to the activity of stem cells called supporting cells.

“The first thing a supporting cell needs to do is sense that there is an injury and divide into progeny that will mature into hair cells,” says Ksenia Gnedeva, assistant professor of otolaryngology – head and neck surgery and stem cell biology and regenerative medicine at the Keck School of Medicine of USC. “That doesn’t happen in mammals. The very first step is blocked.”

Gnedeva discovered that a molecular cascade called the Hippo signaling pathway acts like a brake on that first step in regeneration in mammals. Then, she identified a small molecule that blocks the main enzyme in the pathway called the LATS kinase that can switch the cascade from a brake to an accelerator.

“When we applied the kinase inhibitor to inner ear sensory organs from mice, we saw something that had never been published before,” Gnedeva says. “All of the supporting cells were now able to reenter the cell cycle,” meaning that they began actively dividing in the petri dish. Remarkably, some of them grew into hair cells.

Gnedeva’s lab is now investigating how to effectively deliver this compound into the inner ear to restore hair cells in living mice. The hope is that the therapy may one day work to regenerate hair cells in humans and restore hearing to those with severe hearing loss.

 

KNEES

In your joints, a strong, flexible connective tissue called cartilage provides padding between bones and acts as a shock absorber and lubricant. Osteoarthritis occurs when the cartilage is compromised due to injury or aging, causing the bones to rub against each other, often painfully.

Very few stem cells are present in adult cartilage, meaning the tissue doesn’t naturally regenerate. Historically, treatments for osteoarthritis have been limited to painkillers and invasive surgery to replace damaged joints. But Denis Evseenko — professor of orthopedic surgery, stem cell biology and regenerative medicine, vice chair for research of orthopedic surgery and director of skeletal regeneration at the Keck School of Medicine of USC — and his collaborators have innovated new stem-cell-based treatments that promise to make osteoarthritis pain a thing of the past.

One is a “regenerative pouch” to replace cartilage that’s been damaged by a fall, sports injury or other trauma. The pouch, which is being developed by Evseenko’s startup company Plurocart, contains hundreds of thousands of young cartilage cells derived from stem cells. “It’s a little reparative structure that you can surgically deliver right into the cartilage defect,” Evseenko says.

In animal models, the pouches have shown phenomenal results: The juvenile cells grow into mature cartilage, preventing osteoarthritis. Evseenko is now planning the first clinical trial in humans with knee injuries.

Evseenko’s lab has also created a therapy for age-related osteoarthritis that is being developed by his startup company CarthroniX. As we age and cartilage is progressively lost, painful inflammation can set in. “Chronic inflammation is a signal for local stem cells that it’s a bad environment and they should not build new tissue,” Evseenko says.

He identified a compound that disrupts a key immune receptor’s over-activation due to inflammation. When this compound is injected into the knees of patients with mild to moderate osteoarthritis, inflammation is suppressed, stem cells are activated to slowly regrow tissue and pain is significantly reduced.

HEART

After a heart attack, many people go on to lead productive lives — but the heart muscle itself is forever changed. Since adult heart cells do not regenerate, the scar tissue formed in areas of the heart attack can compromise the heart’s ability to pump. Over time, reduced function can lead to heart failure, depending on the amount of scar tissue and the size of the heart attack.

Murry, the head of USC Stem Cell, has discovered a way to use heart cells derived from stem cells to strengthen hearts damaged by scar tissue. “By transplanting these heart muscle cells, we can rebuild the heart and restore its contractile function,” Murry says.

He likens the process to growing a garden: The injured heart becomes the soil where stem-cell-derived heart cells are planted. The “roots” are the connective tissue and blood vessels that the new cells call in to feed them. Murry anticipates that clinical trials of the transplanted cells will begin within the next couple of years.

Megan McCain, associate professor of biomedical engineering at the USC Viterbi School of Engineering and of stem cell biology and regenerative medicine at the Keck School of Medicine, has innovated complex living tissue models from human stem cells that allow her to visualize heart scar tissue formation in real time.

Her team seeds quarter-size silicone wafers with stem cell-derived heart muscle cells. As the cells grow, they align and begin to beat together much as they would in an actual human heart. McCain can then induce what she calls a “heart attack on a chip” — by selectively depriving some of the cells of oxygen — and observe how the cells remodel themselves after the injury.

“The next step is to develop interventions to change how the heart heals itself,” McCain says, to reduce how much scar tissue forms in the first place.

Vaughn Starnes, chair and distinguished professor of surgery at the Keck School of Medicine and founding executive director of Keck Medicine’s USC Cardiac and Vascular Institute, is exploring stem cells as a treatment for children born with a congenital condition called hypoplastic left heart syndrome. In those affected, the left side of the heart is underdeveloped, leaving the baby with one, instead of two, functioning ventricles to pump blood. Over time, the single ventricle fails in 10% to 15% of patients.

Early evidence suggests that when stem cells from a baby’s own umbilical cord blood are differentiated into heart cells and injected into that ventricle, they strengthen the muscle and improve its function — potentially reducing the chances of failure down the line.

KIDNEY

Our kidneys are vital organs to sustain life. They filter waste products from our blood and produce urine we excrete. Because of the increasing prevalence of diseases that injure the kidneys, including hypertension and diabetes, chronic kidney disease is on the rise in the United States, affecting one in seven adults.

Kidney transplants can save lives — but the demand for donor kidneys far exceeds the supply. Each day, an estimated 13 Americans die waiting for a kidney transplant.

Zhongwei Li, assistant professor of medicine and stem cell biology and regenerative medicine at the Keck School of Medicine of USC, has pioneered a “synthetic kidney” using human stem cells that may soon provide an alternative to kidney transplants from a donor.

The architecture of a human kidney is complex. A million functional units called nephrons organize themselves into a treelike structure to drain the urine they produce. Once injured, nephrons can’t regenerate. Li developed a method for turning stem cells into kidney progenitor cells, the cell type necessary for kidney development in a human embryo.

“By using those building-block progenitor cells, we have successfully assembled a treelike structure with nephrons attached to the structure in a petri dish,” Li says.

His team has demonstrated that these “kidney organoids,” when transplanted into animal models, can grow into synthetic kidneys that produce urine just like natural kidneys. Li anticipates that within five to 10 years, the technology will be advanced enough for clinical trials in humans.

As he works with collaborators in fields including kidney development, 3D bioprinting and kidney physiology to perfect the synthetic kidney’s design, Li stresses that the power of his innovation comes from nature itself.

“Progenitor cells are hardwired to build a treelike structure,” Li says. “We direct the cells to do what they’re programmed to do.”

PANCREAS

For the more than 38 million Americans with diabetes, the disease significantly affects daily life and poses long-term health risks. While it can be managed with medication, diet and lifestyle, there’s currently no cure.

Diabetes occurs when your blood sugar is too high, either because your pancreas makes little or no insulin (Type 1 diabetes) or your cells don’t use insulin properly (Type 2 diabetes). In the latter condition, your pancreas may be producing insulin — just not enough to keep your blood sugar in the normal range.

“Whether it’s Type 1 or Type 2 diabetes, fundamentally you need more functional insulin cells,” says Senta Georgia, associate professor of pediatrics and stem cell biology and regenerative medicine at the Keck School of Medicine of USC. “For a number of years, my lab has been working on ways to make insulin cells from stem cells, trying to understand the barriers that exist and improve the processes that underlie how we make these cells.”

Georgia aims to support the development of clinical regenerative therapies for diabetes. These may one day include transplanting stem cell-derived insulin cells into the pancreas, coaxing a patient’s pancreas to make more of its own insulin cells or improving the function of existing insulin cells.

One of her lab’s current areas of focus is investigating why COVID-19 infections sharply increase the risk of developing Type 2 diabetes. Her team is using stem cell models to understand the virus’ impact on insulin cell function and survival, with an eye toward identifying and blocking pathways to injury.

They’re also collaborating with clinicians at CHLA to study the cells of pediatric patients with genetic forms of diabetes. A recent project illuminated the critical importance of a gene called NEUROGENIN3 in enabling stem cells to mature into insulin cells. Children with a mutation in this gene develop a severe form of diabetes.

CELLS

While many USC researchers are employing stem cells to regenerate damaged tissues and organs, Ian Ehrenreich — divisional dean for life sciences and professor of biological sciences at the USC Dornsife College of Letters, Arts and Sciences — is pioneering new ways to modify stem cells themselves.

Genetically modified stem cells hold great promise for therapeutic purposes. Ehrenreich points to one recently developed example: the first FDA-approved gene therapy for patients with sickle cell anemia, a blood disorder caused by a genetic mutation. In this therapy, the blood stem cells of patients are modified by genome editing and transplanted back into patients’ bone marrow, where they produce a protein that prevents the “sickling” of red blood cells.

“The type of genetic engineering involved in this therapy is simple,” Ehrenreich says. “They’re breaking one genetic element. But a lot of things we’re going to need to do [to develop new stem-cell therapeutics] are going to require more sophisticated genetic engineering. That’s the realm where my lab works.”

He and his team have developed new techniques for building large pieces of DNA (synthetic chromosomes), involving less time and cost than ever before possible. “These big DNA constructs will be important for reprogramming stem cells to serve particular tasks,” Ehrenreich says. DNA synthesized using these techniques could also be added to a stem cell to compensate for genes that a patient is missing.

One of Ehrenreich’s intracampus collaborations is with Leonardo Morsut, assistant professor of stem cell biology and regenerative medicine at the Keck School of Medicine of USC. Morsut engineers stem cells to divide in particular ways to grow tissues of desired structure and function. Employing large synthetic chromosomes from Ehrenreich’s lab “might enable more complex programming of these cells, which could be beneficial in eventually making [synthetic] organs,” Ehrenreich says.

About 10 years ago, when George Salem was in his mid-50s, a friend invited him to play a round of golf. He accepted the invitation — even though the associate professor in the USC Division of Biokinesiology and Physical Therapy had never taken golf seriously. A former college football player, he favored more vigorous sports like snowboarding, basketball and rugby.

But when he joined his friend’s foursome, Salem found himself riveted by the action on the greens and fairways. The course was crowded with silver-haired players, many in their 80s and 90s. He struck up conversations with individuals who had survived cancer and strokes, undergone hip and knee replacements, and were grappling with Parkinson’s disease. And during play, these older golfers left Salem in the dust.

“I was amazed at how much better at golf they were than I was,” he says. “But more importantly, I was amazed at how they could get in and out of a sand trap, climb hills, track a ball and mentally strategize which club to use and how to shoot.”

An expert in exercise and aging, Salem wondered if golf itself was helping to keep these players physically robust and cognitively sharp despite their health challenges. Right there on the links, a new research direction was born.

For millennia, humans have been searching for ways to extend life and remedy the ravages of aging, pursuing mythical springs, miracle elixirs and science-based biohacks. In recent decades, as life expectancies have increased, the desire to thrive as we age has only intensified.

But quality-of-life challenges still loom for an older adult population growing at an unprecedented pace. This includes rising rates of age-related chronic diseases, social isolation and elder abuse.

Now an avid golfer and director of the USC Institute for Therapeutic Golf Science, Salem is among the many USC scholars in wide-ranging fields whose innovative research is meeting these challenges head-on — and redefining the path to longevity in the process. Whether leveraging science and technology or harnessing the power of community, USC researchers are making leading-edge discoveries that can guide the choices we make today for a healthier and happier tomorrow.

“USC is uniquely positioned to chart new territory in our understanding of longevity and healthy aging,” says Pinchas Cohen, dean of the USC Leonard Davis School of Gerontology, which is the nation’s first and largest educational institute on aging. “We are unmatched in our constellation of resources to support patients, families and caregivers and develop visionary new ways to increase both lifespan and healthspan — years spent free of disease.”

You Are What You (Don’t) Eat

THOUGH THE PASSAGE of time is a constant, the rate at which we age varies from one person to another.

Scientists make a distinction between your chronological age and your biological age, the latter being a measure of the functional state of your body’s systems and damage that’s occurred to your cells and tissues. If your biological age is greater than your chronological age, you’re more likely to develop age-related diseases including dementia, stroke and more. While genetics influence the pace of biological aging, making healthy lifestyle choices can slow it down — or possibly put it in reverse.

One of the most important choices is what you put on your plate. Exploring a century of research on long-lived populations around the world, Valter Longo, professor of gerontology and biological sciences at USC Leonard Davis, developed recommendations for a “longevity diet” that is rich in legumes, whole grains, vegetables, nuts, olive oil and some fish, and low in red and processed meats, sugar and refined grains.

But his research also demonstrates the benefits of taking breaks from eating abundantly. A recent study Longo conducted with Sebastian Brandhorst, associate professor of gerontology, and other collaborators reveals that periodically adopting a “fasting-mimicking diet” (FMD) — which contains ingredients that simulate fasting and drastically limits calorie intake for five days — can shave years off your biological age. In the study, adults who completed three FMD cycles over several months slashed their biological age by an average of 2 1/2 years, and their insulin resistance and other pre-diabetic markers improved.

“Humans and many other organisms evolved during long periods when we didn’t have food,” Longo says. His lab’s animal studies suggest that when our hunter-gatherer ancestors feasted after a period of famine, a process called cellular reprogramming kicked in so that shrunken cells, organs and tissues could be rebuilt and restored. “The fasting-mimicking diet is tapping into this ability of the system to detect damage and then begin a process of self-repair and regeneration,” he says.

Longo has shown that in mice, periodic FMD cycles reduce harmful inflammation, kill cancer cells and improve markers of Alzheimer’s disease in the brain. Early research suggests they may do the same in people. Longo’s discoveries have been leveraged by his company L-Nutra to create FMD kits for general health and tailored to specific diseases including diabetes, cancer and Alzheimer’s.

Teeing Up for Play Time

OUR PREHISTORIC predecessors’ survival depended upon physical fitness, as hunter-gatherers had to outrun predators and prey. Now, if we hope to outrun age-related diseases, staying active is vital.

“Exercise is the magic pill,” says George Salem, noting that regular physical activity improves sleep and immunity, bolsters brain health and mental health, and decreases the chances of dying from any cause.

Over the past decade, Salem has conducted a series of studies on older adults, including veterans and prostate cancer survivors, who learn to play golf. He’s shown that in as few as 10 weeks, participation in the sport — which gets players striding up and down inclines and squatting to place and recover balls — increases walking ability and balance, improves performance on cognitive and memory tests, and reduces blood markers of inflammation.

The mental and social aspects of golf contribute to these benefits. As golfers strategize shots and fraternize with their peers, they’re stimulating their brains and engaging in what keeps Salem himself committed to the sport: play. “It’s more fun to play than it is to exercise,” he says.

Many of the participants in Salem’s studies express a desire to continue golfing after the introductory lessons end. “Once you’re hooked, you’re hooked,” Salem says. “Golfers will go out in the pouring rain and out in the snow. They show up because they’re playing with friends who expect them to show up.”

That level of investment in a fitness-boosting activity may help explain why golfers live five years longer on average than nongolfers. But if teeing off isn’t your cup of tea, don’t despair. “Other recreational activities, including pickleball and ballroom dancing, are likely just as beneficial,” Salem notes.

Ready, Tech, Go!

NO MATTER HOW physically fit you are, sedentary behavior poses a significant threat to longevity. Sitting for long periods of time without breaks has been linked to a higher risk of heart disease, diabetes, cancer and death — even among those who exercise. Older adults with mobility issues, chronic pain and other health conditions are especially vulnerable to sitting for hours upon end.

At the Healthy Aging Research and Technology Lab in the USC Mrs. T.H. Chan Division of Occupational Science and Occupational Therapy, Stacey Schepens Niemiec, associate professor of research, is developing new tools to help older people reduce their amount of sedentary time. These tools incorporate both low-tech and high-tech solutions.

One is a smartphone app called Moving Up that tracks the number of hours users spend immobile and offers customized suggestions for integrating more movement into their self-reported activities. For example, if the user is watching television, the app may alert them to drink more water — not only for extra hydration, but to encourage more frequent walks to and from the bathroom.

Schepens Niemiec is also collaborating on the development of an active seating system that incorporates pedals — like a stationary bike, but without wheels — and sensors that track seated time. The system prompts users to pedal for a couple of minutes at regular intervals to counter the negative side effects of long periods of immobile sitting like stiffness and reduced blood flow.

It may seem against the grain to develop technological solutions for an older population, given that younger consumers are more often the assumed end users of the latest tech. But Schepens Niemiec is aiming to fill a gap. “The older adult population tends to get overlooked when it comes to tech-driven innovations,” she says. “Right from the start, I get older adults’ input in the design of the technology to help make it more accessible to them.”

Now Hear This

ONE TECHNOLOGY for older adults that has greatly advanced in the past decade is hearing aids, which are smaller and have better sound quality than the devices of yesteryear. Yet only one in 10 of the approximately 40 million American adults who need hearing aids use them — likely due to a variety of factors, including cost and social stigma.

“A good number of patients tell me, ‘I don’t want to look old by wearing hearing aids,’” says Janet Choi, an otolaryngologyist with Keck Medicine and assistant professor at the Keck School of Medicine of USC.

That mindset can be self-defeating — because using hearing aids may help you live longer. Groundbreaking research by Choi and her collaborators revealed that among those with hearing loss, regular hearing aid users are almost 25% less likely to die from any cause than those who never wear them.

Though more research is needed to untangle why hearing aid use boosts lifespan, it’s possible that it confers protection against diseases linked to untreated hearing loss, including dementia and depression. “Some studies suggest that the sound input provided by hearing aids may have a positive impact on brain structures,” Choi says.

Choi is now researching ways to encourage hearing aid use among older people and counter social stigma associated with the devices, which she relates to from personal experience. The specialist in ear-related disorders was born with hearing loss in her left ear and now wears a hearing aid. But she didn’t do so as a child because her parents were worried she would be ridiculed at school.

It took Choi three tries before she found the right hearing aid for herself. Knowing that the time-intensive selection process can be a barrier to use, she’s developing an AI-driven database that helps match patients with hearing aids best suited to their unique needs.

Shore Up Support

WHEN OLDER ADULTS with hearing loss adopt hearing aids, they’re better able to participate in conversations and stay engaged socially, buffering themselves from isolation. That itself may boost longevity: Feeling isolated makes it more likely you’ll develop dementia, depression, heart disease and stroke, and die prematurely.

Interdependence with others is critical throughout our lives. But as we age and need help with the tasks of daily living, interpersonal dynamics shift. Our adult children or spouse may step in to take care of us.

“That can be a wonderful new opportunity for a deepening love,” says Laura Mosqueda, professor of family medicine and geriatrics at Keck School of Medicine. “And it could also be an opportunity for abuse or neglect.”

One in 10 older adults is abused or neglected in their lifetime, and among those with Alzheimer’s or other dementias, the rate jumps to nearly one in two. Most commonly, the person carrying out the abuse is a close family member.

In her research on the causes of elder abuse, Mosqueda has found that abusive behavior is often rooted in caregivers’ difficulty coping with their demanding roles. “Eighty percent of abuse and neglect is preventable,” she says. “We need to look for the early warning signs: caregivers who are stressed, resentful, burdened and unhappy.”

Along with her collaborator Bonnie Olsen, professor of clinical family medicine and vice chair for research at Keck School of Medicine, Mosqueda is investigating how best to detect these signs and intervene by equipping caregivers with tactics for elder care and self-care. They’re one of several teams at USC working to support caregivers’ well-being and, by extension, the well-being of the older adults in their care.

At the USC Family Caregiver Support Center (FCSC) directed by Donna Benton, associate professor of gerontology, innovative research includes studies on how best to support dementia caregivers and how technology can improve caregiving. The FCSC also runs support groups and helplines for care-givers throughout the Los Angeles area, with groups such as the one at the First AME Church near the USC University Park Campus supporting diverse and low-income communities.

Tapping into the power of community to ease the challenges of modern aging is also a focus for María Aranda, professor in the USC Suzanne Dworak-Peck School of Social Work and director of the USC Edward R. Roybal Institute on Aging. Aranda conducts intervention research with English- and Spanish-speaking caregivers in the communities surrounding USC and has found that family caregivers of loved ones with medical conditions feel less alone in their journeys when they join supportive groups and share resources. Older adults who nurture community connections fare better, too, given the increased sense of purpose and emotional attachments.

“Whether it’s leisure activities, social activities related to their house of worship, or relationships with family, friends or neighbors, people who have a sense of purpose and meaning are likely to have a longer and more enjoyable life,” Aranda says.

Her insights affirm what Salem observed that pivotal day on the fairway. Social connectedness is a driving force of human thriving — whether on the golf course or over the course of a life well-lived.

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Your Cells on Aging

Inside your body’s cells, structures called mitocho­ndria create the energy needed to carry out vital life processes. Cellular aging begins in these power­ houses. “Mitochondria are the first part of our cells to experience dysfunction as we age,” says Pinchas Cohen, dean of the USC Leonard Davis School of Ger­ontology and Distinguished Professor of gerontology, medicine and biological sciences.

Cohen and his collaborators have identified a series of microproteins produced by the mitochon­dria that naturally decrease with age and whose decline is linked to the onset of age­related diseases. His lab’s remarkable discoveries include mitochon­drial microproteins that protect against Alzheimer’s disease, Parkinson’s disease and diabetes, and are associated with longer life spans.

To sustain life, cells rely on a set of chemical reac­tions known as cell metabolism, which produces sub­stances called metabolites. Peter Mullen, assistant professor of molecular microbiology and immunology at the Keck School of Medicine and USC Leonard Davis, along with his collaborators, have identified multiple metabolites in the organs of mice that decrease sig­nificantly with age and whose reduction is associated with organ dysfunction. Many of these metabolites can also predict biological age in humans.

Both mitochondrial microproteins and metabo­lites have the potential to become tools of “precision longevity.” They may one day form the basis of drugs tailored to the specific cellular deficiencies of each individual to treat disease and prolong life. — Rachel B. Levin