Two researchers in the University of Alabama at Birmingham Department of Pathology were recently awarded R01 grants from the National Institutes of Health totaling $4.9 million.
Tyrrell awarded $3 million to study atherosclerosis in aging adults
Daniel Tyrrell, Ph.D., an assistant professor in the Division of Molecular and Cellular Pathology, recently received funding from the National Institutes of Health’s National Heart, Lung, and Blood Institute, for his project titled “Age-associated cytotoxic T cell mechanisms of atherosclerosis.” The five-year, $3 million study will run through March 2031.
Diseases linked to atherosclerosis, or the hardening of artery walls, such as heart disease, are the leading cause of death in the United States. Although aging is the strongest known risk for atherosclerosis, there is a significant gap in understanding how aging promotes the condition.
“We found that, later in life, a specific type of cytotoxic T cell expresses an enzyme called granzyme K, which accumulates in atherosclerotic lesions,” Tyrrell said. “We’re trying to figure out what drives the buildup of this type of cell in old age, and how granzyme K may be driving atherosclerosis.”
In addition to granzyme K, Tyrrell found a unique T cell population accumulated in elderly humans and mouse models, known as age-associated T cells. Age-associated T cells make up more than 55 percent of all T cells in atherosclerotic plaques; however, its contribution to atherosclerosis has not been explored. Tyrrell’s research team will test their hypothesis by using a combination of in vitro and in vivo animal models.
“Our goal in this project is twofold,” Tyrrell said. “We want to determine what drives the accumulation of age-associated T cells in old age and how granzyme K may be driving atherosclerosis.”
“We’re hopeful that the outcome of this study will provide valuable insights into the roles of both granzyme K and age-associated T cells in atherosclerosis, which could lead to the development of novel therapeutic strategies for coronary artery disease in older adults.”
Other UAB collaborators include Silvio Litovsky, M.D., Department of Pathology; Allan Zajac, Ph.D., Department of Microbiology; and Jianmei Wu Leavenworth, M.D., Department of Neurosurgery.
Ding receives $1.9 million to study MYC-driven cancers
Han-Fei Ding, Ph.D., Gene P. Siegal Endowed Professor in the Division of Molecular Pathology, was recently awarded $1.9 million by the National Institutes of Health National Cancer Institute for his project titled “PUS7-tRNA axis in translational control of MYC-driven transcription and metabolic reprogramming.”
MYC-driven cancers are characterized by the overactivation of the MYC family of oncogenes. Healthy MYC oncoproteins are regulators of cell growth and metabolism; but when driven by cancer, they can contribute to rapid tumor growth and avoid immune responses. MYC-driven cancers account for more than half of human cancers and are a major cause of mortality.
Ding’s project will specifically examine how a cancer-controlled enzyme, PUS7, adds a chemical marker to tRNAs to boost the production of proteins that tumors need. It will also test practical strategies to block this pathway.
By defining how this pathway controls tumor cells and metabolic adaptation, the study aims to uncover new treatment strategies for patients with MYC-driven cancers.
“We believe, once we determine exactly how these tumor cells are being controlled, we can take steps toward developing new therapeutics to prevent this disease mechanism in aggressive cancers,” Ding said.