Dr. Kolliputi awarded NIH grants to study liver fibrosis, lung injury syndromes
Narasaiah Kolliputi, PhD, associate professor in the Department of Internal Medicine, Division of Allergy and Immunology, recently received a new two-year, $392,437 R21 award from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) to explore the role of a messenger RNA-binding protein called tristetraprolin (TTP) in alcohol-induced liver fibrosis.
This is Dr. Kolliputi’s second active NIH grant. In 2016 he was also awarded a $373,750 R56 from the National Heart, Lung and Blood Institute investigating the mechanisms that cause lung injury and acute respiratory distress syndrome (ARDS).
The build-up of scar tissue in the liver over time (fibrosis) can lead to a more serious outcome: cirrhosis. Liver fibrosis/cirrhosis is one of the leading causes of illness and death in the world, and alcohol abuse is responsible for more than 50 percent of liver cirrhosis cases in Western countries.
Alcohol-induced proliferation of fibrous tissue in the liver evolves from an imbalance between cell signaling molecules known as cytokines and the activation of hepatic stellate cells. This disruption affects the differentiation of smooth muscle cells into myofibroblasts involved in inflammatory response to injury.
Dr. Kolliputi’s laboratory will work to shed light on the regulatory mechanisms involved in liver fibrosis pathology, including determining whether TPP suppression is critical for alcohol-induced fibrosis. Reducing these profibrotic mechanisms will be an important step towards developing new therapies to reduce or reverse fibrosis, Dr. Kolliputi said.
In his NIH-supported ARDS research, Dr. Kolliputi focuses on mechanisms of cytokine imbalance, through the study of inflammasomes, and aims to find a way to check the abnormal immune response and inflammation that lead to a build-up of fluid in the lungs. In ARDS tiny air sacs in the lungs fill abnormally and can no longer move oxygen the way they should. That means even a patient on a ventilator may not get enough oxygen into their blood.
Dr. Kolliputi and colleagues have found that clearing a toxic molecule (such as 4-hydroxy-2-nonenal) can preserve mitochondrial function and attenuate acute lung injury. Using mouse models, they are exploring this mitochondrial pathway for potential therapies that may improve survival and quality of life for people with acute lung injury.
Dr. Kolliputi also holds an appointment in the Department of Molecular Medicine, the Department of Pediatrics, and the Department of Pharmaceutical Sciences.