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TU, LIBR partnership at the forefront of mental health research 

The Laureate Institute for Brain Research opened its doors 10 years ago to address one of Oklahoma’s worst health factors, mental health. As scientists and researchers discover the ways in which a person’s mental health is directly linked to their overall physical condition, LIBR, in collaboration with The University of Tulsa, is using new neuroscience tools and resources to answer old questions about Oklahoma’s health crisis.

LIBR
Director Martin Paulus

LIBR was founded by the William K. Warren Foundation when then scientific director Wayne Drevets and five other colleagues from the National Institutes of Health in Washington, D.C., transferred to Tulsa in 2009. Today, the organization includes seven principal investigators (PI) who have tenure track or tenure appointments in the OU-TU School of Community Medicine. The goal then and now is to conduct neuroscience-based research that will improve the diagnosis or prognosis of individuals with mental illness. LIBR Director Martin Paulus said the institute strives to respect the dignity of each patient while leveraging leading talent and technology to discover the causes of and cures for disorders related to mood, anxiety, eating and memory. “We’re trying to use neuroscience to find better ways to develop mental health interventions,” he said.

T-1000

When Paulus joined the LIBR staff in 2014, he set a goal to create a large data set that would allow researchers to investigate mental health prognosis and diagnosis through behavioral processes, neuroimaging, neuromodulation, psychophysiology and bioassays. LIBR’s largest research project, the Tulsa 1000 (T-1000) study, began recruiting participants with mood, anxiety, eating and substance disorders to complete more than 24 hours of baseline testing. The 1,000th and final individual was enrolled in 2018 with the goal of determining whether neuroscience-based measures can be used to predict outcomes in patients with mental illness.
Data Analytics Lead Rayus Kuplicki (B.S. ’09, M.S. ’11, Ph.D. ’14) has been heavily involved in the technical setup and analysis of T-1000 since its inception. He said the standardization of this initial data collection at the institute is critical for quality research. “My work has made it possible to take raw data from thousands of participants and compute the quantifiable traits that we compare across groups,” he explained.

LIBR
TU graduate student Bart Ford

Data analysis of T-1000 participants continues and has generated more than 40 scientific papers, currently in progress. TU graduate students in the areas of psychology, engineering and biology contribute to T-1000 research through subsets of data analysis. Biology doctoral student Bart Ford is collaborating with LIBR PI Jonathan Savitz to examine the link between latent viruses and depression. “It is well established that early life stress and childhood trauma increase the risk of physical and mental health problems later in life, but the biological mechanisms by which this occurs are not well understood,” Ford said. “Dr. Savitz and I wondered if people who experience childhood abuse and neglect are perhaps more vulnerable to a common latent herpes virus called cytomegalovirus (CMV).”

The virus is usually harmless in otherwise healthy individuals but can weaken the immune system over time. Savitz and Ford studied a group of individuals with major depressive disorder and found that higher levels of self-reported childhood abuse and neglect were associated with a greater likelihood of testing positive for CMV. They then used the T-1000 cohort to replicate the study and discovered the same results with similar effects in size. The findings were published in the prestigious “JAMA Psychiatry” journal earlier this year.
“We interpret this to mean that the stress of abuse and neglect during development may render a person susceptible to a CMV infection,” Ford stated. “This could suggest CMV contributes to later life health problems that are often seen in survivors of abuse.”

According to Savitz and Ford, T-1000 is beneficial in understanding the biological causes, mechanisms and outcomes of mental health disorders, and consequently, can help identify therapeutic targets that will lead to treatments of the sources and after-effects of mental illness.

ABCD

In addition to T-1000, another primary project ongoing at LIBR is the Adolescent Brain Cognitive Development (ABCD) initiative, a study of more than 11,878 children, ages 9 and 10, at 21 different sites nationwide. LIBR researchers have conducted detailed assessments of 743 of the participants. Follow-up visits and scans will continue for 10 years to examine the course of wellness and mental illness during the second decade of life when mental health disorders tend to emerge. One of the first papers the data generated in 2018 was accepted to the journal “NeuroImage” and entitled “Screen media activity and brain structure in youth: Evidence for diverse structural correlation networks from the ABCD study.”

TU Tough

LIBR
Professor Robin Aupperle

Robin Aupperle is another LIBR PI and assistant professor of community medicine who uses neuroscience and psychological research to improve mental health and gain insight into the causes of anxiety, depression and trauma. She is interested in identifying factors that support resilience to college-related stress and strategies to optimize a student’s psychological well-being. Paulus said meta-analyses show one in three students will develop significant anxiety and depression during their first year of college — a major reason why some students choose to drop out of school. That’s why Aupperle developed the four-week TU Tough program that teaches the skills and mindset necessary for mental toughness to effectively respond to stressful or challenging situations. “This is the idea that our abilities are not set in stone — that we can learn, improve and adapt,” she explained. “Likewise, our ability to be resilient in the face of stress is not hard-wired but can be built and strengthened through practicing certain skills as we seek out and face challenges.”

Aupperle is a mentor to graduate students such as TU clinical psychology Ph.D. student Tim McDermott. His predoctoral training grant application to the National Institute of Mental Health received a qualifying score for funding, which will support McDermott’s research to study the brain circuits underlying people’s ability to manage their emotional reactions. Understanding the brain circuits involved in the processing and regulating of emotions could potentially inform future anxiety and depression treatments. “We will examine whether individuals can learn to regulate their prefrontal cortex activation during emotional processing in response to feedback about their brain activation during functional magnetic resonance imaging (fMRI) scanning,” he said.

As an assistant in the TU Tough project, McDermott has led lectures in TU Tough modules and supervised small group leaders during breakout discussions. He also has managed data processing and analysis for fMRI neuroimaging scans performed before and after TU Tough treatment. Prepared by lead author Elisabeth Akeman (BS ’15) as well as Aupperle and McDermott, a recently published manuscript in the journal “Depression and Anxiety” reports findings from the first two cohorts of TU Tough. The research shows students who complete the program (compared to those who did not) experienced lower rates of self-reported stress and depression symptoms throughout their first semester of college, particularly as measured during finals week. Aupperle explained TU Tough is a strong example of LIBR research that can improve the overall mental health of Oklahomans. “By taking measures to improve resilience to stress and mental health among TU students, we are benefiting the community in general,” she said. “Supporting the health and well-being of our students is the equivalent to supporting the health and well-being of our community.”

LIBR
TU graduate student McKenna Pierson

Other ongoing treatment studies at LIBR use behavioral activation or cognitive behavioral therapy (as part of ongoing studies in Aupperle’s lab) or novel intervention approaches such as the Float Clinic and Research Center led by PI Justin Feinstein. His studies use flotation as an intervention approach to mental illness, providing patients with a way to disconnect with the world and reconnect with signals firing in their bodies. His research was featured on the CBS This Morning’s “Pay Attention” series in 2018.

TU and LIBR’s unique partnership

Paulus is pleased with the substantial data collection, analyses and treatment LIBR has been able to provide to residents within its first decade. Although Oklahoma has a long way to go in improving its overall mental health, he explained LIBR intends to serve as the starting point for large sets of basic health information that support a biotech approach to mental health treatment and diagnosis. “We want to know how far we can develop, how advanced is our research and can we potentially establish startups that can be developed into effective treatments and commercial products,” Paulus said. In one example, LIBR Chief Technology Officer and physicist Jerzy Bodurka, created a way to use a real-time MRI to train a specific part of the brain to give instant feedback on if the training is effective. Paulus explained the training has reduced levels of depression in research participants, and Bodurka now is developing a turnkey system that will allow for scalability of the intervention at any site with MRI imaging capabilities.

LIBRBehind every principal or associate investigator stands a team of student researchers eager to get involved, serving as valuable assets for LIBR’s mission. When asked if TU depends on LIBR or if LIBR relies on TU, Paulus said the partnership is unique in that it is based on both concepts; while the institute focuses on quality research, TU is a generator of knowledge. “TU’s primary mission is teaching, but the goal of our faculty is to be top-level researchers,” Paulus said. “The research provides training opportunities for students, and we couldn’t train them if we didn’t have this relationship with TU.”

Close ties to LIBR are an incentive for students, especially those at the graduate level, to choose TU for advanced experience in their field of research. Students are invited to participate in rotations through the institute and contribute to the facility’s mental health mission. Although LIBR’s primary method of research is brain imaging, Paulus said there will be opportunities for additional biology-based research in the future as researchers pursue exciting advancements into the new decade.

High school seniors perform cutting-edge research as TURC Junior Scholars

This summer, The University of Tulsa is hosting 13 rising high school seniors from the Tulsa area and surrounding communities as TURC Junior Scholars. The program stems from the nationally recognized Tulsa Undergraduate Research Challenge (TURC), which allows standout high school students to engage with tenured and tenure-track faculty in the university’s state-of-the-art laboratories. The Junior TURC program has hosted more than 70 high school students since its establishment in 2012.

Researching workout supplements

Seerut Parmar, a senior at Holland Hall, has been working with Gordon Purser, a TU chemistry professor. The two have taken on a project to determine whether a workout supplement is providing the extra boost that it claims.

Junior TURC
Professor Purser and Parmar

Purser explained that the supplement, l-arginine ethyl ester, has been endorsed by athletes for several years, but “we haven’t found any evidence in the literature to support that position.”

As a TURC Junior Scholar, Parmar has the opportunity to look for such evidence or disprove the claims altogether. The high schooler was not shaken by being thrust into an academic environment at the university level.

“I felt prepared coming in,” she said. “I had to adapt and learn things about arginine that I didn’t know, but the people at TU helped me feel included and engaged from the first day. They made the transition from an AP Chem classroom to an actual research project a comfortable one.”

Purser, likewise, had nothing but good things to say about Parmar and the Junior TURC program.

“The high school students do not have the preparation of TU students – they haven’t had organic chemistry here, for example. But they’re also exceptional students from around the Tulsa area, so with very little guidance, they can come into the program and make a big impact. Working with Seerut this summer has been a pleasure. Nobody has been more eager to help and driven to learn.”

As the team continues researching, Parmar is laying the foundation for a potential career. She wants to double major in chemistry and journalism in college, planning a future where she can explore “writing with chemistry, or doing chemistry with writing.”

Studying disease in cotton

In the Department of Biological Sciences, Junior TURC scholar David Steichen is working with TU Associate Professor Akhtar Ali on a project about mycoviruses, or viruses that infect fungi.

Junior TURC
Professor Ali and Steichen

One of these fungi, Fusarium oxysporum, has destroyed large percentages of cotton crops in Texas and will only continue to spread if no remedy is found. Since cotton is a major cash crop of the southwest, a deadly fungi could significantly damage the economy.

Steichen and Ali are working to prevent this. Their research with mycoviruses is aimed at using these mycoviruses as a control agent to stop the spread of the fungal disease.

As Steichen explained, “We are trying to isolate the virus and purify it, find its specific RNA, DNA and genetic material, then eventually get that into sequencing.”

Doing so would make the cure achievable.

“After sequencing, we would have to make a solution to drip near the root of every plant,” Ali added. “The virus would be transferred by nature. It would be a solution with no pesticides, no environmental pollution and positive long-term effects.”

In other words, Steichen has spent the summer focusing on research that can help the Midwest economy. Come August, he will return to high school at Bishop Kelley to focus on AP tests and choosing a university to attend next year.

Steichen spoke on this dichotomy of high school life versus college research, saying that he finds joy in both and values them for different things.

Junior TURC
Ali studies a field of cotton infected by the fungi.

“I recently took AP Bio and learned about DNA and how it’s sequenced,” he said, “But never had I actually sequenced it. At TU, after watching, learning and asking a lot of questions, I was able to dive into the research, and being immersed in what I’ve studied helped me truly understand it.”

Ali, regarding the Junior TURC program, said, “It’s a pleasure to work with such bright, intelligent high school students that want to engage with a research project such as this.”

While Steichen hopes to pursue more research or a career as a medical doctor, Ali will continue his research on crops, and both of them will certainly help advance their fields.

“This is a great experience to learn as much as I can to work with college research while in high school,” Steichen said. “I’m seeing how research works and getting a clear path of where I want to go.”

Learn more about the Junior TURC program.

Three faculty named TU Outstanding Researchers

The University of Tulsa honored its inaugural group of Outstanding Researchers at spring commencement on May 4. The Outstanding Researcher Award is a lifetime distinction, received only once in an individual’s career. It is intended to honor career-spanning achievements that have been validated in the scholar’s professional field.

These are the 2018-19 recipients:

outstanding researchersRose F. Gamble, Tandy Professor of Computer Science Engineering. Gamble developed a safety and security requirements model that can be embedded and used by a self-adaptive system to intelligently determine the least risky adaptation to deploy at runtime.

outstanding researchersJamie L. Rhudy, Director of the Psychophysiology Laboratory for Affective Neuroscience and Professor of Psychology. Rhudy’s research identifies mechanisms that contribute to and/or maintain chronic pain (particularly in Native Americans) and seeks to develop non-invasive methods for assessing individuals at risk for developing chronic pain.

Outstanding ResearchersCem Sarica, F.H. “Mick” Merelli/Cimarex Energy Professor of Petroleum Engineering. Sarica’s research has been disseminated to the public at large through more than 240 publications and incorporated in various software. He has been recognized internationally with several awards by the Society of Petroleum Engineers, most notably with an SPE John Franklin Carll Award in 2015.

Candidates for the Outstanding Researcher awards were nominated by deans from the Kendall College of Arts and Sciences, College of Engineering and Natural Sciences, Collins College of Business and the Oxley College of Health Sciences. Nominees were selected for their recognition of outstanding research and scholarship achievements based on a single project or a cumulative contribution.

Other considerations included pedagogical awards, honors from scholarly societies, grants, publication citation counts or other forms of public recognition. External recognition of a faculty member’s work also factored into the selection process.

Learn more about this year’s distinguished faculty awards, including the 2018-19 Outstanding Teachers and Medicine Wheel Award recipients.

TU students place first and second at statewide research competition

Two students from The University of Tulsa College of Engineering and Natural Sciences received top honors at the 2019 Research Day at the Capitol in Oklahoma City.

sarah gutierrez
Gutierrez with Chancellor Glen D. Johnson

Chemical engineering junior Sarah A. Gutierrez of Broken Arrow, Oklahoma, and chemistry junior Marjorie Sheaff of Owasso, Oklahoma, were among 22 undergraduate students representing 16 Oklahoma colleges and universities at the event in March. Gutierrez won first place in the research-intensive campus category for her plasma catalysis research. Sheaff earned second place in the research-intensive campus category for her conductive 3D printing research.

marjorie sheaff
Sheaff with Chancellor Glen D. Johnson

They presented competitive research posters to the State Legislature and the public during the annual event, sponsored by Oklahoma NSF EPSCoR, the Oklahoma State Regents for Higher Education and the National Science Foundation. The event is designed to raise awareness of the outstanding research that is taking place at Oklahoma’s colleges and universities.

TU receives more than $1M in DoD funding

roger maillerThe University of Tulsa will soon improve its interdisciplinary research and training with a new Department of Defense award received by Associate Professor of Computer Science Roger Mailler. The Defense University Research Instrumentation Program (DURIP) award, totaling more than $1 million, will allow faculty working in neuroscience to purchase a state-of-the-art scanning confocal microscope that can provide a clearer picture of individual neurons.

“The system will be used like an fMRI (functional magnetic resonance imaging), similar to the one used to study humans,” Mailler said. “Instead of measuring how a nervous system produces behavior on a scale of tens of thousands of neurons, this system does it on the scale of individual neurons.”

The microscope will be used to reverse engineer the nervous system of roundworms in ongoing research titled “Choosing a Direction: Neural Models of Decision Making.” In this study, Mailler and a group of TU scientists will investigate how these creatures regulate their speed and direction. Roundworms, or specifically Caenorhabditis elegans, exhibit qualities of autonomy and adaptability. Researchers in this project hope that it will be a stepping stone toward developing advanced, adaptive machines that can recognize and respond to the outside world, also known as intelligent systems.

According to Mailler, “The technology is the most sophisticated technique available, relying on the fusion of genetic engineering, cutting-edge optics and advanced image processing and data analysis.”

The technology can essentially analyze individual neurons and reverse engineer nervous systems using light. This empowers more than just current research projects, but also opens the door to pioneering discoveries in multiple disciplines.

In addition to the benefits to TU researchers, it also affords students the opportunity to train on cutting-edge technology that will set them apart in science, technology, engineering and math fields. This award opens access to one-of-a-kind tools exceeding anything available in the southcentral United States, distinguishing TU as a True Blue institution for faculty and student-researchers alike.