Huang Lab Publishes JCI Insight Study on RNA Polymerase, R-Loops, and Bone Marrow Failure in Fanconi Anemia

SAN ANTONIO, Texas — The Huang Lab at the Mays Cancer Center at UT Health San Antonio announces a new study in JCI Insight: "Insights and modulation of RNA polymerase-dependent R-loop and dsRNA in Fanconi anemia hematopoietic stem cells." The article was published February 26, 2026, and appears in Volume 11, Issue 7. Authors are Michihiro Hashimoto, Xiaomin Feng, Jie Bai, Huimin Zeng, Tian Li, Jue Li, Terumasa Umemoto, Paul R. Andreassen, and Gang Huang.

Fanconi anemia is the most common inherited bone marrow failure syndrome, yet how the disease drives that failure has been hard to study because deleting a single Fanconi anemia gene in mice does not reproduce it. To close that gap, the team built a new mouse model that pairs loss of Fanca with reduced Setd2, a regulator that restrains transcription by RNA polymerases. The model develops severe bone marrow failure that more closely mirrors the human disease.

Across patient-derived cells and stem cells from the new model, the authors found shared defects. R-loops and double-stranded RNA accumulated, ribosome production faltered, and stem cells showed cell cycle arrest and errors during division. These features link transcription-driven genomic stress to the collapse of blood-forming stem cells.

The study also points to a possible treatment. Juglone, a pan-RNA polymerase inhibitor, lowered R-loop and double-stranded RNA levels, restored ribosome biogenesis, reduced division errors, and rescued bone marrow failure in the model. The findings nominate inhibition of RNA polymerases as a therapeutic avenue worth further preclinical study, potentially making safer autologous approaches more feasible for patients.

"This model finally lets us study why the bone marrow fails in Fanconi anemia, not just that it does," said Dr. Gang Huang, principal investigator and corresponding author. "Showing that an RNA polymerase inhibitor can rescue stem cell function opens a direction beyond transplantation that we are eager to pursue."

DOI: https://doi.org/10.1172/jci.insight.192126

About the Huang Lab

The Huang Lab at UT Health San Antonio is a basic and translational cancer research group within the MD Anderson Mays Cancer Center at UT Health San Antonio. Our team integrates hematology and solid tumor biology with immunology and metabolism to uncover mechanisms and design interventions. We advance cell and biologic therapies, including CAR T-cell approaches for solid tumors. We also conduct research in trauma and military health. We move discoveries toward clinical impact through product development and collaborations with clinicians and industry. Education and mentorship are core to our mission. We train students, postdoctoral fellows, and early-career scientists in rigorous, multidisciplinary research. Together, we aim to deliver therapies and technologies that improve patient outcomes.