May 7, 2024

CPOD Faculty Publication Spotlight - Coleman Lab

Kaur G, Wu B, Murali S, Lanigan T, Coleman RM. The FASEB Journal. 29 February 2024. A synthetic, closed-looped gene circuit for the autonomous regulation of RUNX2 activity during chondrogenesis.
"Runt-related transcription factor 2 (RUNX2) has a significant role in cartilage tissue during development and subsequent maturation in disease states after cartilage injury. Using the principles of synthetic biology, we have created a gene circuit that allows cells to autonomously control their RUNX2 levels through negative-feedback regulation, allowing them to dynamically adjust the level of silencing required to maintain steady states levels of RUNX2 suppression without needing to address the specific pathways underlying cartilage maturation in response to the microenvironment of the injured joint (e.g., elevated inflammation). We show that our autoregulatory gene circuit enhanced matrix accumulation and resisted ECM degradation by reprogrammed stem cell-derived cartilage cells in response to inflammatory stimulus. Our results demonstrate that cell-autonomous regulation of intracellular messengers can enhance cartilage tissue regeneration and is a viable alternative to strategies that use broad-spectrum spatial/temporal regulation of exogenous cues or constitutive or transient silencing of these messengers."
Pictured left to right: Gurcharan Kaur, M.Tech (Ph.D. student, Biomedical Engineering, University of Michigan) and Dr. Rhima Coleman, Ph.D. (Associate Professor, Biomedical Engineering, University of Michigan)