Author: Dan Heller

USC awarded more than $16 million for research on vascular dysfunction, Alzheimer’s disease

Published June 7, 2022Last updated

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NIH awards USC more than $16 million for research on vascular dysfunction and Alzheimer’s disease


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NIH awards USC more than $16 million for research on vascular dysfunction and Alzheimer’s disease

Research funded by the grant will capitalize on the development of biomarkers and advanced imaging by scientists at the Keck School of Medicine of USC to launch studies tracking changes in the blood-brain barrier, neurovascular function and cognition.
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The National Institute on Aging, a division of the National Institutes of Health, awarded Berislav Zlokovic, MD, PhD, director of the Zilkha Neurogenetic Institute, and Arthur W. Toga, PhD, director of the USC Mark and Mary Stevens Neuroimaging and Informatics Institute (Stevens INI), $16.1 million to continue research on the role that blood vessel dysfunction plays in the development of dementia and Alzheimer’s disease.

“There is increasing evidence that neurovasculature has a major role in early cognitive decline,” said Zlokovic, chair and professor of physiology and neurosciences at the Keck School of Medicine of USC. “This grant allows us to continue important research on how changes in the blood-brain barrier and blood flow interact with amyloid-beta and tau pathology to trigger structural and functional changes in the brain, leading to cognitive impairment and early Alzheimer’s disease.”

More than 30 years ago, Zlokovic was among the first to propose that flaws in the blood-brain barrier, which keeps harmful substances in the blood from moving into brain tissue, could be the early, underlying cause of most cognitive disorders, rather than the accumulation of amyloid beta plaque, which had long been the focus of Alzheimer’s research. With this award, he and his colleagues can further test this so-called neurovascular hypothesis.

“This work will build on our earlier work, which has shown that people can progress to mild cognitive impairment, independent of amyloid beta and tau if the blood-brain barrier is damaged,” said Zlokovic.

Documenting Alzheimer’s disease progression

The funding will allow the team of researchers to launch longitudinal studies comparing the progress of more than 400 people who have a genetic variant putting them at high risk for developing Alzheimer’s disease — known as apolipoprotein E4 (APOE4) — with more than 450 people with APOE3, a different variant which puts them at lower risk for developing Alzheimer’s disease.

About 75% of the participants will be cognitively unimpaired at the start of the study and about 25% will have only mild impairment. The researchers will follow them for five years, tracking changes in the blood-brain barrier, blood flow and the brain’s structure and function while monitoring participants for cognitive impairment, using neuroimaging and molecular biomarkers indicating blood vessel dysfunction, which were developed by Zlokovic, and advanced brain imaging technology developed by Toga.

“Using our ultra-high field 7T magnetic resonance imaging (MRI) scanner has transformed our understanding of how fluid-filled regions in the brain — perivascular spaces — impact brain health. Here at the Stevens INI, we have successfully used this advanced imaging to facilitate breakthroughs, including the central role that perivascular space plays in brain changes associated with aging, including neurodegenerative disorders,” said Toga, Provost Professor of Ophthalmology, Neurology, Psychiatry and the Behavioral Sciences, Radiology and Engineering at the Keck School of Medicine. “Our imaging capabilities have allowed us to create a multimodal assessment of the role of neurovasculature in cognitive decline, a comprehensive research program on perivascular spaces, and numerous close-up investigations of how fluids travel through the brain, including via the blood-brain barrier. I’m thrilled to have received this funding to continue our work in partnership with Dr. Zlokovic.”

Researchers hope the work will lead to a better understanding of the onset and progression of Alzheimer’s disease and the identification of the best interventions for different stages of the disease.

Testing treatments in the lab

Simultaneously, the team will conduct complementary laboratory research using mice that have been genetically altered to carry human APOE gene variants to help document changes in the brain that lead to cognitive decline and to test a potential treatment.

The treatment is an experimental neuroprotective enzyme co-developed by Zlokovic’s team, in collaboration with John Griffin, PhD, from the Scripps Research Institute, called 3K3A-APC, an engineered form of human activated protein C. Researchers will test it in the altered mice to see if it can protect the integrity of the blood-brain barrier and prevent cognitive decline. In addition they hope to examine whether this type of intervention is effective at the earliest signs of vascular dysfunction or at later stages of disease in mouse models that also have amyloid beta and tau. The National Institute of Neurological Disorders and Stroke (NINDS) recently awarded funding for a pivotal Phase 3 clinical trial of 3K3A-APC in stroke patients, led by Patrick Lyden, MD, professor of physiology and neuroscience at the Zilkha Neurogenetic Institute.

“We hope that the results of this research will eventually lead us to new treatments for people with the APOE4 gene,” said Zlokovic.

Turning biomarkers into a blood test for Alzheimer’s disease

Zlokovic added that they continue to improve on key molecular biomarkers, and he hopes eventually to discover biomarkers detectible in blood, which would make the process of identifying people at risk for Alzheimer’s disease simpler and more accessible.

“We have been pursuing several avenues of research that all complement one another,” said Zlokovic. “We believe that this research will contribute to important new findings about the pathogenesis of cognitive decline and will also lead to development of important new therapies for cognitive impairment, dementia and Alzheimer’s disease.”

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USC researchers simulate how COVID-19 transmits in a classroom

Published June 7, 2022

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USC Researchers Simulate COVID-19 Classroom Transmission

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USC Researchers Simulate COVID-19 Classroom Transmission

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With coronavirus cases rising again in nearly every US state, the big question is: how can we stay safe while resuming normal life, particularly in crowded spaces such as college campuses? Over the past two years, decision-makers have been forced to make choices about everything from vaccination and mask mandates to occupancy limits, based on ever-changing assumptions about COVID-19.

Now, USC researchers have helped quantify the effectiveness of some of the most debated mitigation strategies by simulating the spread of COVID-19 on a university campus, specifically modeling airborne transmission risks associated with in-person classes.

The new study, published in the Proceedings of the National Academy of Sciences (PNAS), shows that during the highly transmissible Delta variant outbreak, at least 93% of students should be vaccinated, with everyone wearing masks indoors, to prevent an uptick in cases. For the original COVID-19 strain, 23% of students should be vaccinated, with everyone wearing masks indoors (or 64% of students without mask usage).

These findings will help decision-makers in the event of ongoing COVID-19 outbreaks or an outbreak of a similar infectious disease. The simulation model also allows decision-makers to explore “what-if” scenarios relating to the spread of COVID-19 in classrooms by varying parameters to see the outcome under different scenarios, such as hybrid classes, current vaccination rates, masking protocols, community infection levels, and varying levels of virus infectiousness.

“I think the hardest thing about the pandemic has been finding the right balance–there is a tension between having some sort of normalcy to go about our lives, and also keeping ourselves safe,” said study co-author Bhaskar Krishnamachari, a professor of electrical and computer engineering and computer science.

“This paper contributes to more clear-headed thinking about when we can be in a mode of operating in person, with or without masks, and when we need to mandate vaccines. We have felt our way around many of these things over the past two years, but this gives us a more concrete, data-driven process to go by. It doesn’t have to be an arbitrary or political decision. This tells us that scientifically, there is nuance.”

Titled “Simulating COVID-19 Classroom Transmission on a University Campus,” the study is authored by Arvin Hekmati, a computer science Ph.D. student; Mitul Luhar, a professor of aerospace and mechanical engineering; Bhaskar Krishnamachari, a professor of electrical and computer engineering and computer science; and Maja Matari?, a professor of computer science, neuroscience and pediatrics.

Highly granular data

The research is particularly relevant during the early days of an infectious disease outbreak when policymakers face the difficult decision of decreeing school closures. Using a simulation of COVID-19 spread based on real anonymized data from a large university, the researchers projected the impact of various school reopening strategies: complete closure, hybrid, in-person; vaccinated and unvaccinated; masked and unmasked.

In a first-of-its-kind study, the model accounts for highly granular data such as class schedules, classroom sizes, occupancy, ventilation rates, as well as vaccine rate and efficacy, and even information specific to classroom interactions, such as the role of speech and disease transmission in an enclosed space.

“Nothing needs to be made by assumptions; we can quantify every aspect of this epidemic and come up with the best decision.” Arvin Hekmati.

The results showed that without vaccination, moving 90% of classes online can reduce new infections by as much as 94%, while universal mask usage can reduce new infections by up to 72%.

“With this tool, universities do not need to make these decisions without knowledge – they can make informed decisions for university policies to keep it safe for students, faculty, and staff,” said Hekmati. “Nothing needs to be made by assumptions; we can quantify every aspect of this epidemic and come up with the best decision.”

Opportunity and responsibility

Researchers from computer science, electrical engineering and aerospace engineering fields teamed up to work on this paper, which draws on expertise in both large-scale computer modeling and the mechanistic transmission modeling of COVID-19.

“As a university, we have an opportunity and responsibility to study our own community in order to gain insights to inform the broader public,” said Matari?.

“This project was tremendously satisfying because it brought together colleagues from multiple Viterbi School departments who enabled the analysis and modeling, which in turn provided insights into safety policies for university campuses during pandemic conditions.”

To inform the model, Professor Luhar, an expert on modeling indoor airborne dispersion, analyzed the mechanisms of COVID-19 transmission, considering everything from room size to the number of people present, and how much they speak–all of which can result in variability in virus emission rates from instructors and students.

During lectures, for instance, instructors will tend to speak significantly more often than students, which could influence transmission rates. “Providing those facts in the model made it very compatible in the cases of universities and classrooms,” said Hekmati.

In future work, the team hopes to expand their research to include a tool that could be used by campus administrators at large universities and workplace campuses. While this model is specifically designed for classrooms, there are many modular aspects that could be tweaked to extend to other types of environments, said the researchers.

“Nothing gives us more satisfaction as researchers in engineering than to have a positive impact on society,” said Krishnamachari, who also serves as Hekmati’s advisor. “Most of us, when we started engineering school, we had this dream that we do work that is meaningful, that helps others, and I’m very happy for Arvin that he has worked on a project where he can see that kind of positive impact.”

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Julia M. Ritter named dean of the USC Kaufman School of Dance

Published June 6, 2022

USC has named dance scholar Julia M. Ritter as dean of the USC Kaufman School of Dance, effective July 1.

Ritter is currently a professor of dance at the Mason Gross School of the Arts at Rutgers University, where she served as chair and artistic director of the department of dance from 2010 to 2021. At Rutgers, she launched wide-ranging curricular and programmatic initiatives, establishing two new graduate degrees, multiple study abroad programs– and numerous community creative engagement projects.

“Throughout her career, Julia Ritter has championed dance not only as a means of self-expression, but as a way to communicate and connect with others,” USC President Carol L. Folt said. “She is a creative, compassionate leader who cares deeply about students and helps them develop lifelong careers in dance.

She is a creative, compassionate leader who cares deeply about students and helps them develop lifelong careers in dance.

Carol L. Folt, USC president

“At USC, she will work closely with Kaufman students, faculty, staff and alumni to strengthen our vibrant arts community — and build even broader and deeper ties with our campus partners, Los Angeles and the world.”

An award-winning dance artist and scholar, Ritter has worked at the intersection of the arts, humanities and sciences to engage with social justice and community building. Her 2021 book Tandem Dances: Choreographing Immersive Performance examines the role of dance in the emerging field of immersive theater and performance.

“Over the past several years, the USC Kaufman community has created a program of education and performance that is changing dance as a creative discipline. The progress is nothing short of remarkable,” USC Provost Charles F. Zukoski said. “We now aim higher. We have found the leader who will enable us to achieve our aspirations. We can build on that foundation to strengthen our global leadership in the dance world, recruit the best students and train them to flourish in challenging and satisfying careers.”

Founded in 2012, USC Kaufman is known for its innovative New Movement educational model, which combines rigorous dance training with interdisciplinary studies and cross-campus collaboration.

“I am so excited to join USC Kaufman because of what has already been established here, including the stellar faculty and students, the Glorya Kaufman International Dance Center and the New Movement curriculum,” Ritter said. “I know that there is an incredible amount of innovation happening across USC right now, and I feel there are no limits to how we can ideate and collaborate.”

New USC Kaufman dean: a commitment to interdisciplinarity

Crossing disciplines has been the hallmark of Ritter’s career. “During my undergraduate training at Rutgers, I was lucky to study with faculty who prioritized collaboration,” she said. “I studied with people like Don Redlich, who exemplified how to build partnerships with musicians, costume designers, set designers. Coming from that lineage helped me understand the interdisciplinary nature and potential of the arts.”

While earning her Master of Fine Arts at Temple University, Ritter studied with Brenda Dixon Gottschild, a leading scholar of African diasporic dance forms. “She introduced me to even more collaborative processes and ways of thinking about dance from different cultural lenses,” she said.

Her doctoral studies at Texas Woman’s University focused on immersive performance, an emerging field that bridges theater, dance, film and digital media. “As I’ve been studying these new ways to collaborate throughout my career, I’ve seen a real hunger from both faculty and students to build institutional and creative infrastructures that support those kinds of interactions,” she said.

While leading the Department of Dance at Rutgers, she pioneered projects with other schools, including environmental and biological sciences, engineering and the Institute for the Study of Global Racial Justice. She also co-founded the Integrated Dance Collaboratory, which brings together artists and scientists to explore the full spectrum of dance’s unique rehabilitative, therapeutic and expressive potential. “Producing projects that have an impact across campus and beyond is part of my DNA,” she said.

Exploring choreography and society

In recognition of her interdisciplinary excellence, Ritter received the inaugural Rutgers Presidential Outstanding Faculty Scholar Award in 2021. Other significant recognitions for Ritter include three Fulbright Scholar awards for choreographic research. Her work has been additionally funded by a host of state and national organizations committed to the role of arts in society, and she has presented her scholarship and choreography at conferences and arts venues across the globe.

Ritter’s book Tandem Dances “explores how choreography functions as a structural mechanism for mobilizing audiences during immersive live performances,” she said. “We’re living in an experience economy: People don’t want to simply watch something on the stage; they want to be in that world. We can now understand choreography as the composing of dancers’ movements and as a mechanism for organizing the kinesthetic experience of the spectator.”

Ritter notes that choreography can also be used in building diverse and inclusive communities through dance.

“One way to do that is through curriculum — to help our students build a literacy of different dance and choreographic forms through historical and cultural understanding,” she said. “I’m looking forward to brainstorming with USC faculty about creating platforms for USC Kaufman that are inclusive across all communities.”

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Uncertainty casts a shadow on 2022 Summit of the Americas

Published June 6, 2022

Confusion reigned leading up to the ninth Summit of the Americas that convenes in Los Angeles today.

President Joe Biden will take part, but uncertainty over which heads of state will attend could limit opportunities for coordination on key issues affecting Latin America and the United States. The agenda centers on the summit’s theme, “Building a Sustainable, Resilient, and Equitable Future.”

USC Professor Gerardo Munck — an expert on comparative politics in Latin America — will moderate a panel discussion Friday about “The State of Democracy in Latin American and the World.” Munck, a professor of political science and international relations at the USC Dornsife College of Letters, Arts and Sciences, will discuss these issues with a group featuring two former heads of state: Leonel Fern?ndez, former president of the Dominican Republic, and Laura Chinchilla, former president of Costa Rica. We spoke to him recently about the summit, his view on democracies in the Western Hemisphere and why this year’s summit may be limited in scope.

What is the state of democracy in Latin America and the Western hemisphere?

The positive is that if you compare Latin America to other developing regions, it’s the region that is most democratic. There was a big wave of democratization in the 1980s and ’90s where nearly all the countries but Cuba became democratic. You have Venezuela and Nicaragua joining Cuba as Spanish-speaking countries with dictatorships, but this is the best time for democracy in Latin America’s history. In the past, the region had democracies, but they didn’t endure. Now, we have democracies that have lasted 40 years or so.

However, people have a perception that these democracies are not working well, that politicians are corrupt, and sometimes even use money from drug cartels for electoral purposes. There’s a sense that the elites are distant from the people, leading to a sense of a crisis of representation.

Where have democracies fallen short of fulfilling their promises?

People expected that after several decades of democracy, something would be done to reduce economic inequality. Early in the century, some countries managed to reduce inequality. But this progress wasn’t sustained, and it led people to ask: “Is democracy working for me?” It’s the same issue we’re facing here in the United States, but in Latin America it is accompanied by another factor: a tremendous level of violence. A statistic I use in my classes shows that since 2000, roughly 2.4 million people have been killed in Latin America. These murders are committed by drug cartels, gangs, common criminals, and state agents. Latin America is the most violent region in the world. People expect things from democracy — basic things like security — and democracies have failed to deliver what citizens want.

How do these democracies compare to those in the United States and Western Europe?

An area where Latin America has shown growth is the inclusion of women in politics. Nearly every country in the region has gender quotas, and these quotas have worked. The [average] percentage of women in the lower chambers of congress is slightly over 30%, which puts it in line with Western Europe and ahead of the United States. In the United States, 28% of the members of the [House of Representatives] in 2022 are women, but we were close to 20% very recently. Seven Latin American countries have elected female presidents. Countries that are more culturally conservative than the United States have made steps to improve the representation of women. This is a very positive trend.

One major topic surrounding the 2022 Summit of the Americas is that numerous heads of state are wavering on their commitment to attend. Mexican President Andr?s Manuel L?pez Obrador threatened to stay home unless Cuba, Nicaragua and Venezuela were included. Why is the United States declining to invite these countries to the summit?

The host country has the authority to pick or invite which leaders and countries to invite to the summit. The United States is totally entitled … not to invite the heads of state of Venezuela, Nicaragua and Cuba [Nicol?s Maduro, Daniel Ortega and Miguel D?az-Canel].

This has been an issue at the last several summits. On the left and right of the political spectrum, Latin American leaders have argued that all leaders should be invited.

When Cuban President Ra?l Castro was invited to the summit in Panama in 2015, we witnessed the historic meeting of Ra?l Castro and U.S. President Barack Obama.

What are the potential consequences of not having all countries represented at the Summit of the Americas?

The United States is doing the right thing in sending a signal that dictators should be criticized. The question is whether President Biden is weakening the United States’ standing if his decision [not to invite those leaders] causes President L?pez Obrador of Mexico not to attend the summit. The United States could have pursued [the option] to invite all leaders from Latin America and then foster a discussion about how to better protect democracy in Latin America and the United States. This option would have been preferable.

What could result from the summit?

Summits usually generate some energy going forward about things of collective interest in the hemisphere. During the first summit in 1994, for example, President Bill Clinton and the other presidents and prime ministers of the hemisphere agreed to a pathbreaking plan to develop a Free Trade Area of the Americas. NAFTA [the North American Free Trade Agreement] had been negotiated with Mexico and Canada and went into effect in January 1994. A plan was developed to apply that model to foster greater economic integration in the Americas. It was a hugely ambitious, 10-year project, and it eventually failed – there was pushback from leaders such as [Venezuelan] President Hugo Ch?vez.

Another more successful initiative occurred at the 2001 summit in Peru, [where] the Inter-American Democratic Charter was approved. I do not expect anything as ambitious coming out of the 2022 summit in Los Angeles. I think this will be a missed opportunity.

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Children’s Hospital Los Angeles awarded $3 million to study opioid use in hospitalized infants

Published June 6, 2022

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Children’s Hospital Los Angeles Awarded $3 Million to Study Opioid Use in Hospitalized Infants

CHLA researchers received a grant to study the long-term influence of opioids, a class of powerful painkillers, on hospitalized, critically ill infants.
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Children’s Hospital Los Angeles received a significant 5-year grant to study the long-term impact of opioids on infants. While these powerful painkillers help with recovery, opioids can have serious side effects on an infant’s brain and body.

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) awarded the study more than $3 million. Principal Investigator and pediatric surgeon Lorraine Kelley-Quon, MD, will lead the study in collaboration with other CHLA investigators and researchers from Ohio State University’s Nationwide Children’s Hospital and Stanford University School of Medicine. Dr. Kelley-Quon is also an assistant professor of surgery and population and public health sciences at the Keck School of Medicine of USC.

“The opioid epidemic continues to impact children in the United States including the youngest and most vulnerable,” says Dr. Kelley-Quon. She believes the study will spark important change.

Risks of opioid use in infants

Opioids used in the hospital, such as hydromorphone, morphine and fentanyl, are necessary to help a critically ill infant tolerate life-sustaining interventions or recover from surgery. If an infant’s pain is not sufficiently controlled in the hospital, the child may have future developmental disability. However, prolonged and excess opioid exposures can also hinder an infant’s brain development. Problems with thinking, language and movement can surface by 18-36 months old.

Research has linked early opioid exposure with the development of mental disabilities and an increased need for health care later in life.

Past research has focused on infant health after substance exposure in the womb. However, few studies have looked at doctor-directed opioid use in hospitalized infants.

“Our goal with this research is to find the sweet spot,” says Dr. Kelley-Quon. “We aim to determine how doctors can best control a critically ill infant’s discomfort during hospitalization while minimizing the long-term risks associated with prolonged or excess opioid use.”

Each year, more than 200,000 hospitalized infants receive opioids for pain relief. Decisions about which infants receive opioids, the amount of medication given and for how long vary across hospitals. Two infants at different hospitals, but with the same condition and symptoms, may have very different care plans.

Assessing high-risk newborns

Dr. Kelley-Quon and the team of investigators will examine information from California state and national databases about previously hospitalized newborns and their early childhood neurodevelopment. The data will represent a diverse group of high-risk infants.

High-risk infants include newborns with life-threatening brain or heart conditions, severely low birth weight or complications from premature birth. Prolonged pain control with opioids could lead to the development of more health risks in the future.

The team’s novel, large-scale dataset will merge two databases, including data from 2009 to 2020. The first database, the Pediatric Health Information System (PHIS), shares the hospitalization details of children from 52 children’s hospitals nationwide. The PHIS gives researchers access to information such as admission, discharge, diagnosis, procedures, medication usage and surgical treatment. The second database, the California Perinatal Quality Care Collaborative (CPQCC), follows high-risk newborns over time in California and reports on their brain development.

Researchers will uncover the relationship between the amount and length of opioid use in infants and their health outcomes. These outcomes include developmental disabilities and the need for additional health care resources.

The team will also analyze hospitalization costs in relation to opioid use. Factors including ventilator use, amount of intravenous nutrition given and time spent in the hospital all add up. Researchers predict that infants exposed to opioids for longer will need more of these hospital resources, resulting in higher costs.

Creating neonatal pain management guidelines

As a pediatric surgeon, Dr. Kelley-Quon strives to reduce unnecessary opioid prescriptions and use in children. Alongside the American Pediatric Surgical Association, in January 2021, she published the first guidelines for opioid prescribing in children and adolescents after surgery.

Applied in Dr. Kelley-Quon’s previous study, the guidelines led to hospitals safely reducing opioid use in children during recovery from laparoscopic appendectomy. This extremely common, minimally invasive surgery removes a child’s appendix. On average, the number of children sent home with opioid prescriptions decreased by 78%.

With the new study, Dr. Kelley-Quon hopes to develop similar guidelines for opioid use in infants. Not only could the study’s findings decrease unnecessary opioid use, but they could also prompt follow-up care and other resources for newborns who must receive opioids.

Additional investigators on the research team include co-investigators Ashwini Lakshmanan, MD, Ashley Walther, MD, and Cynthia Gong, PhD, of CHLA; Katherine J. Deans, MD, and Jennifer N. Cooper, MD, of Nationwide Children’s Hospital; and Henry Chong Lee, MD, Susan Hintz, MD, and Kanwaljeet Anand, MBBS, PhD, of Stanford University School of Medicine.

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Building reputations as team players — in the lab and on the basketball court

Published June 3, 2022

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USC Stem Cell alumni Litao Tao and Haoze (Vincent) Yu bring their A game to new positions in academia and industry

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USC Stem Cell alumni Litao Tao and Haoze (Vincent) Yu bring their A game to new positions in academia and industry
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Scientists Litao Tao and Haoze (Vincent) Yu were colleagues and team players for many years both inside and outside of Neil Segil’s lab at the Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC. In the lab, they succeeded in making new discoveries about the development of the sensory cells of the inner ear. Meanwhile, on the basketball court, they led their team to victory on many occasions, and also challenged each other during spirited one-on-one matches.

“When we played one-on-one basketball, I was physically stronger,” said Yu, who graduated with his PhD in development, stem cells, and regenerative medicine from USC. “But Litao had the better skillset. Together, we made a great team.”

“Our teamwork also carried over into the research lab,” said Tao, who earned his PhD in genetics, molecular, and cellular biology and completed his postdoctoral training at USC.

Tao grew up in the city of Chongqing in southwest China, and earned his bachelor’s and master’s degrees in biology at Tsinghua University in Beijing. While pursuing his PhD at USC, Tao joined the Segil Lab to study the inner ear.

“The inner ear is like an art piece,” said Tao. “There are multiple cell types, and the sensory cells and the supporting cells interdigitate each other. So I was very interested in how this beautiful organ develops that way.”

While completing his PhD dissertation, Tao began learning more about computational analysis and bioinformatics. He then decided to continue working in the Segil Lab and dedicate his postdoctoral training to next-generation genome sequencing, a new technology for analyzing massive amounts of genetic material to identify variations associated with hearing loss and other diseases.

Tao thrived under the guidance of Segil, who was recently awarded a USC Mentoring Award for fostering an engaging, supportive and inclusive academic environment.

“Neil always encourages his students and postdocs to try new ideas,” said Tao. “If you have a new idea, no matter how baseless it is, you can always talk to him. He will think through it with you, talk about it, and say what the pitfalls and the outcomes might be. And the way he manages the lab, he likes people to be more self-motivated and doesn’t push people for results. So that’s probably the reason why everyone in the Segil Lab is nice, because they don’t feel pressure from him, so they relax and enjoy the research.”

Throughout his years in the Segil Lab, Tao enjoyed one particularly productive way to relax while thinking through complex scientific problems: going fishing.

“When I was in LA, I went fishing almost every weekend,” he said. “I’d cast the baits out, and then I’d sit there. While I was watching for the signals, I could think about work in a low-pressure way. So I’d think of a lot of experiments, or figure out what a problem was. Sometimes you have to jump out of the regular environment, and then you can get new ideas.”

Segil also introduced Tao to Yu, who became a close collaborator and friend. Yu also began his scientific career in China, where he grew up in the northern coastal city of Qingdao. His parents ran a container shipping company, and encouraged Yu to become the first member of their family to earn a college degree.

Yu entered Qingdao’s Ocean University of China as an ecology major. After working in a lab that studied cornea transplants, Yu switched to biology for both his bachelor’s and master’s degrees. He began deriving stem cells from the cornea, and realized that he wanted to continue pursuing biomedical research.

Yu was accepted into the PhD program at USC and joined the Segil Lab, where he learned how the inner ear forms during embryonic development.

Yu also learned a few life lessons along the way.

“Neil didn’t only teach me about the things that we were working on,” said Yu. “He has such great experience as a person. In the early years, he worked in factories, making travel trailers in Salt Lake City. In high school, he traveled to Newfoundland. He tells me a lot of stories about his experience and his friends’ experience. It’s not just academic things.”

Like Tao, Yu was struck by how Segil encouraged him to tap into his own motivation and independence.

“I asked Neil if I could take a break from the lab for a week to go on a hiking trip,” said Yu. “He told me that I’m responsible for my own life, and that I should pursue my own interests and do what I want to do. That’s an attitude I didn’t have growing up in China. But Neil made me realize that from now on, I should be responsible for my own time, my career, and my life. So I went on that trip.”

Yu completed 75 miles of the John Muir Trail stretching from Mammoth Mountain to Yosemite National Park, and summited the tallest mountain in the continental U.S., Mount Whitney.

Yu and Tao also followed Segil’s advice about pursuing their passions in the scientific realm, and served as co-first authors on two studies published in 2021. The first, which appeared in the Proceedings of the National Academy of the Sciences (PNAS), described similarities in the development of two types of sensory cells: the ones that receive sound vibrations in the inner ear, and the ones that sense light touch at the surface of the skin. The second, featured in Developmental Cell, identified a natural barrier to the regeneration of the sensory cells in the inner ear.

Yu also collaborated with scientists from other laboratories in the Department of Stem Cell Biology and Regenerative Medicine. Working with postdoc Katie Galloway from the laboratory of Justin Ichida, Yu explored gene regulation in patients with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, with support from a Doerr Stem Cell Challenge Grant. In 2021, Yu and postdoc Pengfei Xu from the laboratory of Gage Crump co-authored an eLife study about craniofacial development in zebrafish.

Now, Yu and Tao are building on these successes during the next stages of their careers.

After earning his PhD at USC in 2020, Yu completed postdoctoral training in the laboratory of Xin Sun at the University of California, San Diego, where he used computational and bioinformatics approaches to understand lung development in pre-term infants. He is now applying similar approaches to developing stem cell-derived immunotherapies for blood cancers and solid tumors as a scientist at Fate Therapeutics in San Diego.

In 2021, Tao left the Segil Lab to accept a tenure track assistant professor position at Creighton University, studying the biology of the inner ear with a goal of developing new treatments for hearing loss.

However, the two will remain Segil Lab alumni for life.

“There are still projects going on as a collaboration between my new lab and Neil’s lab, so we talk a lot,” said Tao. “Actually, we have a group chat channel with everyone in the Segil Lab. So when someone’s birthday is coming, we say happy birthday to each other. Last week, when I caught a big fish, I sent a picture to everyone.”

Yu added: “Working in the Segil Lab is like a family. He’s like a parent to me. I love him so much, and I made a really important right decision in joining the Segil Lab as a graduate student.”

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‘We will always find our people’: USC kicks off Pride Month with celebration

Published June 2, 2022

When Keck School of Medicine at USC graduate student Carla Ibarra came out as a transgender woman nine years ago, she endured the loss of family members and friends who didn’t want to associate with her anymore. With help from a support network, she learned to stop hating herself and the body she was born in.

“I found the courage, the support, the love, and the community that has fully embraced me for who and what I am,” Ibarra said. “My community’s kindness taught me the power of seeing and loving myself. That … saved my life, and I want to pay my community’s kindness forward.”

On Wednesday, Ibarra shared her story at USC’s kickoff event celebrating Lesbian, Gay, Bisexual, Transgender and Queer Plus (LGBTQ+) Pride Month, themed “The Power of Community.”

USC President Carol L. Folt joined Ibarra and students, faculty and staff members at the virtual event. Earlier that day, the Keck Hospital of USC held a pride flag ceremony for the first time.

Finding power

USC’s LBGTQ+ Student Center supervisor Ab Monz?n said the event’s theme honors Ibarra’s story and others like hers — ways in which LGBTQ+ communities find power by coming together.

Pride celebrations provide opportunities to heal and celebrate. But as numerous anti-LGBTQ+ laws are written and passed across the United States, Monz?n encouraged attendees to “find your community and lend your voice to a collective movement.”

Monz?n added, “Always press for the right to live, to thrive as our authentic selves. … We all deserve the opportunity to figure it out [and] to live the way we want to.”

Creating space

Lindsey Morrison, a process architect at Keck Medicine of USC, described how a teenage experience inspired her to build community in the workplace.

“[I realized that] if [queer] spaces don’t exist to be fully myself, then I can create that,” Morrison said.

So seven years ago, she led a small group of LGBTQ+ staff, faculty and students to create what is now Keck Pride. This resource group helps foster a welcoming environment for LGBTQ+ patients, families and employees across USC’s Health Sciences Campus.

Morrison has found it reassuring to be able to create a community among her colleagues at Keck Medicine of USC.

“The beauty is, I’m never going to be alone,” she said. “We will always find our people.”

A timeless message

In her remarks, President Folt highlighted the ONE Archives at USC Libraries — home to the most extensive collection of LGBTQ+ research materials in the world — and recalled a 1974 invitation to a Hollywood Pride parade that read: “United We Stand.”

That timeless message echoes USC’s theme for this year’s Pride Month, she said, adding: “USC will always be a safe place for our LGBTQIA+ community.”

Shortly before Wednesday’s virtual event, the Progress Pride Flag was raised in front of Keck Hospital of USC. For the first time, it will fly there during the entire month of June.

The Progress Pride Flag adds a five-colored chevron to the classic Rainbow Flag, representing marginalized LGBTQ+ communities of color, along with the colors of the Transgender Pride Flag.

Rodney Hanners, president and CEO of the USC Health System and Keck Medicine CEO, hosted the event with Keck School of Medicine Dean Carolyn C. Melzer. “I couldn’t be happier to join an organization committed to LGBTQ+ health and well-being,” said Melzer, who joined USC in March.

LGBTQ+ Pride Month takes place each June in honor of the 1969 Stonewall uprising in Manhattan, a tipping point for the gay liberation movement in the United States.

A complete list of USC Pride Month events can be found on the university’s event calendar.

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Improving music appreciation for the world’s more than 700,000 cochlear implant users

Published June 2, 2022

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https://keck.usc.edu/improving-music-appreciation-for-the-worlds-more-than-700000-cochlear-implant-users/
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Improving music appreciation for the world’s more than 700,000 cochlear implant users

For more than 700,000 cochlear implant users worldwide, music appreciation is not always what it should be. Dr. Goldsworthy and the Bionic Ear Lab at the USC Caruso Department of Otolaryngology-Head and Neck Surgery are working to change that.
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Sound serves a variety of purposes in our lives. You hear a car’s tires screech and you jump back, preserving your life. Someone calls your name from across the room and you turn to see what they want. Speech is one of the primary forms of communication, helping people connect, share their thoughts, give instructions, receive advice and comfort.

And then there’s music. Twelve simple tones, played on a variety of instruments and in seemingly endless combinations, music may be the ultimate form of the whole being greater than the sum of its parts. Music pumps us up at the gym, it helps us heal in times of heartbreak or grief. It brings people together, it accompanies us in solitude.

No one understands the importance of music more than Dr. Raymond Goldsworthy, head of the Bionic Ear Lab in the USC Caruso Department of Otolaryngology-Head and Neck Surgery. Dr. Goldsworthy lost his hearing at the age of thirteen, just as he was beginning to learn the drums. Like every teenager, he was just beginning his journey into the seemingly limitless world of music, when a bout with spinal meningitis and the ensuing treatment damaged his hearing.

“There is never a good time to lose your hearing, but what was particularly challenging for me at that age was that my friends were discovering new music,” Dr. Goldsworthy remembers. “It hurt that I could not turn to music for comfort during that time.”

He received a cochlear implant, then a relatively new technology that has since become a life-changing device for hundreds of thousands of hard-of-hearing people. Cochlear implants are sound processors that sit behind the ear, catching sound and transmitting it via electrodes that stimulate the auditory nerve. The result is an approximation of hearing that, while perhaps less precise than an average person’s, can help restore a remarkable degree of ability when hearing loss has progressed to the point that a hearing aid is no longer useful.

And, as Dr. Goldsworthy and his researchers at the Bionic Ear Lab have shown, technology can always be improved.

As a music enthusiast and a musician, Dr. Goldsworthy and his team have spent years researching ways to improve the experience of music for cochlear implant users. Their most recent paper (available here), which was co-authored by graduate student Andres Camarena and medical student Grace Manchala, set out to examine exactly how cochlear implant users perceive harmonies.

They did this by setting up an at-home test via a web app, which played two notes together at a time and asked participants to rate what they heard on a scale of pleasantness. The study not only compared cochlear implant users to normal-hearing listeners, but also captured the participant’s musical sophistication — how much they knew about music, how much they’d studied music, their own musicianship.

Previous studies on this topic had concluded that cochlear implant users were largely incapable of distinguishing pleasing or discordant harmonies. This surprised Dr. Goldsworthy, who runs a weekly music appreciation meeting for cochlear implant users (you can read more about the Cochlear Implant Music Hour here), and who had seen first-hand how cochlear implant users were capable of very sophisticated appreciation of melodies and harmonies.

“Science often follows careful observation. Knowing many cochlear implant users who are lifelong musicians allowed my lab to better understand the importance of experience for relearning how to hear subtle differences in harmony,” Dr. Goldsworthy said. “The Cochlear Implant Music Hour showed us that many cochlear implant users have excellent access to harmony.”

The findings of the study were astonishing. While average cochlear implant users indeed had a much rougher perception of pitch changes than the average listener’s (the former were able to hear pitch changes of about 10%, compared with an average listener’s 1%), the highest-performing cochlear implant users were able to distinguish pitch differentiation at about the same rate as average users. More surprising still, the thing that seemed to differentiate ability to hear differences in pitches most among cochlear implant users, aside from the technological issue of being able to hear small modulations in the stimulation that allows the user to hear, was musicianship and musical sophistication.

“The science did naturally follow the observations drawn from the music hour,” Dr. Goldsworthy observed. “We were able to design a listening experiment to carefully characterize harmony perception and to connect that to musicianship.”

This result confirmed what Dr. Goldsworthy had long known from personal experience: that cochlear implant technology can be improved both through technological progress and through the brain’s astonishing ability to learn new skills. Indeed, in his own journey to music appreciation with a cochlear implant, Dr. Goldsworthy discovered that, as technology behind cochlear implants improved, so did his ability to appreciate music — but that, in tandem, just as important was his own evolving appreciation of music as a listener and musician.

“Music appreciation for cochlear implant users is a beautiful meeting of mind and technology,” Dr. Goldsworthy said. “Cochlear implant users can improve their music appreciation by bravely diving into music, but there is also plenty of room to improve how sound is encoded into stimulation to allow recipients to dive even deeper.”

The results of the study provide quite a bit of hope for cochlear implant users longing to enjoy a high-level appreciation of music: they show that a similar level of appreciation to normal-hearing listeners is possible with improving technology and learned musical sophistication. Future research in the Bionic Ear Lab will continue to focus on how to move average cochlear implant users’ experience of music toward the level that the highest-performing cochlear implant users are currently experiencing — in other words, a similar appreciation of music to that of normal-hearing listeners.

“Our research aims to carefully characterize music perception for cochlear implant users. The more precisely we characterize music perception, the better we can improve sound processing for further improvements,” Dr. Goldsworthy said. “I am excited to work with a vibrant team to broadly improve music appreciation for cochlear implant users.”

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