Research Mentor(s): Yuji Mishina, Professor
Research Mentor School/College/Department: Biological and Material Sciences, School of Dentistry
Presentation Date: Thursday, April 22, 2021
Session: Session 3 (1pm-1:50pm)
Breakout Room: Room 7
Fibrodysplasia Ossificans Progressiva (FOP) is a rare genetic condition distinguished by the development of bone in soft tissue, known as heterotopic ossification (HO). FOP is a gain-of-function mutation, causing substitution of an arginine by histidine (R206H) within BMP type 1 receptor ACVR1 protein. This disorder severely impacts an individual’s life, as it leads to body malformations and disabilities. While the exact mechanism of HO progression is still unclear, studies have found that HO development is accompanied with an increase of BMP-SMAD signaling and inflammation. In this research project, we aim to discover methods to decrease HO in FOP mouse models, by attempting to decrease BMP signaling. ACVR1, BMPR1a, and BMPR1b are BMP type 1 receptors. Our previous studies showed that BMP-SMAD dependent signaling is decreased by the knockout of BMPR1a or ACVR1 in specific tissues. By deleting one and/or multiple of these receptors, we predict that it will decrease BMP signaling, ultimately suppressing HO. We use the constitutively active ACVR1 model (caACVR1-Q207D), which develops massive HO within two weeks after activation of BMP signaling with tissue injury. But our study showed our anticipation was wrong. We found that the HO was not inhibited in ACVR1-Q207D mouse model by knocking out BMP type 1 receptors. Additionally, the BMP-SMAD dependent signaling pathway was not inhibited by knocking out BMP type 1 receptors in the HO mouse models. Due to the fact that the outcomes of this project did not support our initial hypothesis, we need to analyze other ways to decrease BMP signaling to suppress HO formation. This research hopes to bring us closer to finding the first effective treatment for FOP/HO, helping the individuals whose lives are permanently impacted by this genetic disease.