Bon Trinh, PhD
A new study published in the journal Blood reveals how a previously unrecognized genetic regulatory circuit helps control the development and function of monocytes and macrophages—two types of white blood cells that play essential roles in fighting infections, clearing damaged tissue, and driving inflammation.
The research was a collaborative effort led by Bon Trinh, PhD, an assistant professor in the Department of Pathology, and investigators from multiple institutions including University of Virginia, Harvard, Tuft, and Virginia Commonwealth University, bringing together expertise in molecular biology, hematology, genomics, and immunology.
“The multi-institutional partnership enabled us to combine advanced genomic analyses with functional studies in cell and animal models to uncover the mechanisms controlling immune cell development and functions,” stated Trinh. UVA faculty contributing to this study include Jeffrey Craig, MD, PhD, Department of Pathology; Golam Mohi, PhD, Department of Biochemistry and Molecular Genetics; Ani Manichaikul, PhD, Department of Genome Sciences; and Adam Goldfarb, MD, Department of Pathology. Among the study’s coauthors were six students from UVA, highlighting the strong involvement of students in research.
Researchers found that two well-known blood cell regulators, PU.1 and C/EBPα, work together with a lesser-known noncoding RNA, LOUP-identified by Dr. Trinh’s team, to guide the formation of these immune cells. Unlike genes that produce proteins, noncoding RNAs help control how genes are turned on and off. The study shows that PU.1 activates LOUP, while LOUP in turn helps sustain PU.1 activity, creating a “feed-forward loop” that reinforces the genetic program needed for monocyte and macrophage development. C/EBPα acts upstream to initiate this circuit. When LOUP levels were reduced, immune cells showed impaired maturation, lower production of inflammatory signaling molecules, and weaker engulfment ability—a key function known as phagocytosis.
“These findings provide new insight into how the immune system is programmed at the molecular level,” said Trinh. “Because abnormal PU.1 and C/EBPα activity has been linked to blood cancers and immune disorders, the newly identified PU.1–LOUP regulatory circuit may offer promising new directions for research into inflammatory diseases and myeloid malignancies such as leukemia.”
By uncovering how coding genes and noncoding RNAs cooperate to control immune cell identity, this collaborative study advances understanding of both normal blood development and disease while highlighting the importance of cross-institutional teamwork in biomedical discovery.
Filed Under: Research