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Collaborating for medical research

TU’s research initiatives extend far beyond the walls of campus laboratories and often recruit the expertise of scientists locally and across the country. Through conference calls, strategic meetings, groundbreaking experiments and exciting review sessions, faculty are solving the mysteries behind some of today’s most debilitating diseases. Medical research spans the range of all STEM disciplines, and TU students join in the action.

Assistant Professor Kyle Simmons is a faculty member in the Tulsa School of Community Medicine and conducts neuroinformatics research at the Laureate Institute for Brain Research (LIBR). He began teaming up with faculty from the College of Engineering and Natural Sciences through a casual work group.

“We recognized the need to build capacity in Tulsa and primarily with TU, which had faculty with experience working in neuroinformatic data,” he said. “I went over to TU every Friday to meet for a type of journal club. We’d sit down in a conference room and discuss an article we’d read.”

Professors Bill Coberly (mathematics), John Hale (computer science), Brett McKinney (computer science) and Richard Redner (mathematics) regularly met with Simmons and became curious about his research.

“I gave them access to resting state fMRI (functional magnetic resonance imaging) data associated with the autism spectrum and neurotypical disorders in kids,” Simmons said. “We took analytical tools of genetic analysis and applied it to neurological networks or brain networks, and out of that came the basic collaboration.”

Research
Graduate student Trang Le, Professor Brett McKinney, senior Sara Douglas and grad student Saeid Parvandeh review gene network data generated at LIBR.

The neurological data generated from resting fMRIs that patients undergo at LIBR allows Simmons to study brain activity in humans noninvasively while they are awake. Sharing the fMRI data with TU provides an opportunity for McKinney to apply sophisticated neuroinformatic approaches to clinical problems and develop new methods for understanding network architecture in the human brain.

This is important because Simmons said scientific evidence shows the intrinsic circuitry associated with sociological infrastructure preconditions is disconnected from the rest of the brain. These sociological preconditions include major depressive disorder (MDD), Simmons’ main research focus. Triggered by an abnormal wiring in the body, MDD also increases individuals’ chances of developing other diseases.

“MDD is the single biggest contributor to those living with disabilities worldwide and the greatest contributor to mortality worldwide,” Simmons said. “We want to answer the question of why is it that someone with a heart disorder is more likely to die if they are depressed — these are important questions.”

With the assistance of biology senior Sara Douglas and math graduate student Trang Le, TU’s ability to analyze LIBR’s fMRI data from MDD patients has proven to be a very valuable partnership. Researchers are beginning to apply recently developed methods to test their effectiveness on completely new data sets.

McKinney also is a faculty member of the Institute for Bioinformatics and Computational Biology, a role that has opened many doors for research. He and Caleb Lareau (BS ’15), a math and biochemistry major at the time, published research in 2015 in collaboration with the Oklahoma Medical Research Foundation (OMRF) in Oklahoma City. Their investigation into gene expression networks led to the development of methods that help researchers understand diseases with an inherited component such as lupus, cardiovascular disease, Alzheimer’s and diabetes.

The most effective way to measure gene expression levels requires novel data that often can be expensive to collect. However, TU works closely with the Mayo Clinic and OMRF where this next-generation data is readily generated. The Mayo Clinic Vaccine Resource Center collaborates with bioinformatics researchers at TU to determine how people respond to vaccines such as influenza.

Other gene expression data targeting MDD is collected through next-generation ribonucleic acid sequencing conducted at OMRF and then passed to McKinney and LIBR for analysis.

“Brett’s team is good at demystifying that kind of data and finding that biology we want,” said Patrick Gaffney, a member of the OMRF Arthritis and Clinical Immunology Research Program and the J.G. Puterbaugh Chair in Medical Research. “We have a genome sequencing core here that generates the data, and Brett and his team do the number crunching.”

Gaffney said research shows factors such as exposure to sun or certain chemical contacts can trigger lupus in genetically predisposed individuals. Lupus and other related diseases are elicited by way of how genetic and environmental components interact.

“It’s a natural affinity for the two groups (TU and OMRF) to work together,” Gaffney said. “We connect information in ways that other people don’t have the experience to do.”

In addition to TU and OMRF, the University of Oklahoma School of Community Medicine is an important part of the medical research collaboration. Kent Teague, associate professor in OU’s Department of Surgery and director of the Integrative Immunology Center, focuses on development of the immune system and the effects of psychosocial and physical stress on the immune system. Labs at the immunology center are responsible for processing blood samples from patients enrolled in brain imaging studies at LIBR, including Simmons’ study previously described. OU processes the blood, analyzes biomarkers related to inflammation found in the serum of these patients, does quantitative polymerase chain reaction work and sends samples to OMRF for next-generation sequencing to assess genes expressed in the white blood cells of these patients, Teague said. “These experiments generate very large amounts of data that require cutting-edge expertise to analyze. McKinney is one of only a handful of investigators in the state with this expertise.”

Teague began working with McKinney in 2010, but he first collaborated with TU faculty on a separate study in 2006. He also joined forces with Pat Bellgowan, formerly at LIBR, and TU athletic trainers in 2010 to conduct research on concussions in student-athletes. That study was published in the Journal of the American Medical Association in 2014. Teague’s involvement with LIBR also involves research with Jonathan Savitz, TU assistant professor in the Tulsa School of Community Medicine and LIBR principal investigator, on the immune system and mood disorders. Together, they have published four scientific manuscripts since 2012.

Teague said it would be impossible for any one of these groups to accomplish their research without collaboration. Specifically, combined expertise and specialized equipment at TU, OU, LIBR and OMRF enable the team to compete for and obtain multiple large National Institutes of Health grants to support the projects.

“This is the nature of research these days in this highly competitive environment with limited funding. To be in a good position to obtain substantial funding, institutions must combine their resources,” Teague said.

In the future, Teague, McKinney and their colleagues anticipate additional collaboration thanks to TU’s new College of Health Sciences and the Tulsa School of Community Medicine.

“I am very optimistic that we will be able to leverage each other’s strengths to achieve much greater success in the future than would have been possible for either institution alone,” Teague said.

To learn more about the College of Health Sciences, please visit healthsciences.utulsa.edu.