UTHealth Houston researchers investigate how proteins that help cells survive hypoxia might be used as therapy for heart and lung diseases

With a seven-year, $6.58 million grant from the National Heart, Lung, and Blood Institute, UTHealth Houston researchers will focuses on hypoxia-inducible factors. (Photo by UTHealth Houston)

The project will be led by Holger K. Eltzschig, MD, PhD, chair and professor in the Department of Anesthesiology, Critical Care and Pain Medicine at McGovern Medical School at UTHealth Houston (Photo by UTHealth Houston)

Scientists at UTHealth Houston are investigating how the body naturally adapts to hypoxia – an insufficient oxygen supply to the body or specific organs – to develop new treatments for life-threatening heart and lung diseases. With a seven-year, $6.58 million grant from the National Heart, Lung, and Blood Institute (R35HL177402), their research focuses on hypoxia-inducible factors (HIFs). These proteins help cells survive oxygen deprivation and regulate inflammation.

Led by Holger K. Eltzschig, MD, PhD, chair and professor in the Department of Anesthesiology, Critical Care and Pain Medicine at McGovern Medical School at UTHealth Houston, the grant, “Targeting Hypoxia-Inducible Factors (HIFS) for Heart and Lung Disease,” will explore ways to utilize HIFs therapeutically.

“At the core of this grant lies the establishment of the Hypoxia-Inflammation Program, a bold and extensive initiative aimed at generating groundbreaking discoveries that will pave the way for innovative strategies to address hypoxia,” said Eltzschig, who is also the John P. and Kathrine G. McGovern Distinguished University Chair at McGovern Medical School and associate vice president for Translational Research and Perioperative Programs at UTHealth Houston.

The program aims to enhance understanding of how to reduce harmful inflammation and protect tissues from further damage by studying the role of HIFs. It will also explore the regulation of HIFs during acute respiratory syndrome, a serious lung condition that occurs when fluid accumulates in the tiny air sacs of the lungs (alveoli). Additionally, it will investigate how HIFs interact with the body’s circadian rhythm and their effects on heart damage during a heart attack.

“We know that HIFs play a critical role in how cells adapt to low oxygen levels. Our research aims to leverage this knowledge to develop better and more innovative therapies for patients with heart and lung conditions,” Eltzschig said.

This project builds on previous National Institutes of Health funded studies that have provided significant insights into inflammation and tissue repair. The new funding, which spans the next seven years, will also support laboratory and clinical studies, as well as training programs for young researchers and medical professionals.

“A key part of the Hypoxia-Inflammation Program is our commitment to training the next generation of researchers. We have a strong track record of research training, with many of our trainees securing NIH funding and becoming independent investigators,” Eltzschig said.

A collaborative, multidisciplinary team of experts from UTHealth Houston and leading institutions worldwide drives the research.

UTHealth Houston researchers will include Xiaoyi Yuan, PhD, assistant professor of anesthesiology, critical care and pain medicine; Kuang-Lei Tsai, PhD, assistant professor of biochemistry and molecular biology; Marie-Françoise Doursout, PhD, professor of anesthesiology, critical care and pain medicine; Matthew DeBerge, PhD, assistant professor of anesthesiology, critical care and pain medicine; Harry Karmouty-Quintana, PhD, associate professor of biochemistry and molecular biology, William S. Kilroy, Sr. Distinguished University Chair in Pulmonary Disease, and director of the Pulmonary Center of Excellence at McGovern Medical School, as well as director of the Molecular and Translational Biology Program at The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences; and Thu Tien Tran, DO, assistant professor of pediatrics.

Additional members of the team are Danny Muehlschlegel, MD, MMSc, MBA, with Johns Hopkins University; Peter Carmeliet, MD, PhD, with Katholieke Universiteit Leuven in Belgium; Sean Colgan, PhD, with the University of Colorado School of Medicine; and Scott Evans, MD, with The University of Texas MD Anderson Cancer Center.

The project is further supported by Jagat Narula, MD, PhD, executive vice president and chief academic officer at UTHealth Houston, as well as professor of cardiology and K. Lance Gould Distinguished University Chair in Coronary Pathophysiology at McGovern Medical School; Dianna Milewicz, MD, PhD, professor and vice chair of the Department of Internal Medicine, President George Bush Chair in Cardiovascular Medicine, and director of the Division of Medical Genetics at McGovern Medical School; Cynthia Ju, PhD, professor, vice chair of Research, and Joseph C. Gabel, MD, Endowed Chair in Anesthesiology at McGovern Medical School; David A. Schwartz, MD, distinguished professor of pulmonary sciences and critical care with the University of Colorado School of Medicine in Denver; and Simon Robson, PhD, MB, ChB, professor of anesthesiology at Harvard Medical School’s Beth Israel Deaconess Medical Center in Boston.