During his 30 years at UTHSC, Hungarian-born Gábor Tigyi, MD, PhD, Harriet Van Vleet Endowment Professor and former chair of the Department of Physiology in the UTHSC College of Medicine, has traveled to his birth country many times. However, in December, the trip back was a milestone. He traveled to Budapest at the invitation of the NOVOFER Foundation for Technical and Intellectual Creation, a nonprofit dedicated to the recognition of scientific and technological discoveries, to receive one of the most prestigious awards of his career: the 2022 Dénes Gábor Prize for scientific innovation.
The award, named after the Nobel Prize winner Dénes Gábor, is given to a Hungarian scientist working abroad who is doing exceptional research with translational applications. Dr. Tigyi’s groundbreaking discoveries in lysophosphatidic acid (LPA) biology are nothing short of revolutionary and have launched an entirely new field of research that today is populated by fellow investigators around the world.
In 1986 at the University of California, Irvine, Dr. Tigyi discovered the lipid mediator LPA. Ten years later at UTHSC, he showed that LPA is able to protect the genetic integrity of intestinal stem cells after radiation exposure, allowing lifesaving tissue recovery. This work garnered him international attention, yielding several patents and a drug compound, Rx100, that is in the FDA approval process for treating radiation injury.
He’s referring to his realization, which came many years later, that LPA is an essential regulator of stem cell pluripotency. “It’s what keeps a stem cell a stem cell,” he said. “With the radiation countermeasure, we were working to help the stem cells survive that energy overload that comes from ionizing radiation. But we were basically working with stem cells and keeping them alive. After 20 years, I’ve come to realize that this LPA molecule is essential for maintaining stemness of stem cells. That’s the real thing.”
Translating the Knowledge
The ways in which this knowledge has been translated into treatments by his UTHSC group and international collaborators sounds like the stuff of science fiction. An example is his work with professors Il-Ho Jang, PhD, Department of Oral Biochemistry and Molecular Biology, and Eun-Jin Seo, Department of Physiology, both faculty at Pusan National University, South Korea, on a project to activate dormant stem cells in the root of the tooth.
“We discovered that if you block the LPA2 cell surface receptor on a stem cell, dental pulp stem cells will grow into odontoblasts, which form dentin the bony part of the tooth,” he said. “When you have a cavity, the bony part of the tooth erodes, exposing the dental pulp in the middle of the tooth. Your dentist solves this by drilling a hole in the tooth, removing the pulp, putting some resin then a cap on your tooth. It’s basically a dead piece of bone. We’ve developed a method where a dentist can instead use a little bit of a gel plug that has been soaked in an inhibitor of the LPA2 receptor, which makes the dental pulp stem cells differentiate into odontoblasts which regrow the tooth. No more filling! We heal the tooth by regeneration, not destruction.”
Another major project, a collaboration with the lab of Duane Miller, PhD, Professor Emeritus in the UTHSC Department of Pharmaceutical Sciences in the College of Pharmacy, is the development of inhibitory compounds that regulate LPA function in malignant cancer stem-like cells that can stop cancer growth and spread.
“We found the second most upregulated gene in cancer stem cells is the enzyme that makes LPA, and it has three fundamental effects: 1) it makes cancer stem cells resistant to radiation and chemotherapy, 2) it makes them spread and metastasize, and 3) it shuts downs the anti-tumor immunity.” Dr. Tigyi is the lead investigator, with Sue Chin Lee, PhD, associate professor in Physiology, as a principal investigator. Also on the team are Corinne Augelli-Szafran, PhD, vice president of Scientific Platforms at Southern Research in Birmingham, Alabama, and Raul Torres, PhD, professor of Immunology and Microbiology at the University of Colorado.
“It’s phenomenal. This has been in our hands such a long time and we didn’t realize,” Dr. Tigyi said, still excited by the discovery. “There’s so much more to do. I wish I were 20 years younger.”
Grateful for Teacher and Collaborators
Since his arrival at UTHSC in 1992, he has been continuously funded by multiple national grants, with the overall amount totaling nearly $70 million to his lab and startup companies. He was named Harriet Van Vleet Chair in Oncology Research in 2006, and associate vice chancellor for Research and Industry Relations in 2016.
Dr. Tigyi received his medical degree from the University Medical School of Pecs, Hungary, and holds a PhD in cellular and molecular neurobiology. His extensive postgraduate work was conducted in biochemistry at the University of Uppsala, Sweden, and at the Max-Planck Institute for Biophysical Chemistry, Gottingen, Germany, as well as the University of California, Irvine.
“I am forever grateful to my teachers. From kindergarten I can name them, all the way to my graduate mentor. They were extraordinary people who taught me a lot more than I realized when I was working with them. They are with me forever.”
He is just as quick to acknowledge his collaborators and co-workers. “The research is not just mine; it belongs in equal part to the people I work with. I’ve had extremely good luck with having good coworkers. I am standing on their shoulders.”