Research
Our laboratory investigates the primary cilium, a specialized cellular antenna that senses and transduces chemical and mechanical signals to regulate essential cellular behaviors. Far more than a passive cellular projection, the primary cilium serves as a critical signaling hub that helps coordinate cell-cell communication and determine cellular responses during embryonic patterning, stem cell differentiation, tissue repair, and organ maintenance. Disruption of ciliary function can profoundly alter these processes, resulting in multisystem disorders collectively known as ciliopathies. Given the essential roles of the skeleton in providing structural support, protecting vital organs, and enabling movement, a major focus of our research is to uncover how primary cilia regulate skeletal development and contribute to skeletal diseases.
The Role of Primary Cilia in Craniofacial Skeletal Development
The formation of the craniofacial skeleton requires extraordinary coordination among multiple cell populations, developmental signals, and tissue interactions. Even subtle disruptions in these processes can result in congenital craniofacial malformations, which represent approximately 30% of all congenital anomalies. Many of these abnormalities originate from defects in cranial neural crest cells (CNCCs), a highly multipotent embryonic cell population that migrates throughout the developing embryo and gives rise to an extensive array of craniofacial tissues, including bone and cartilage. Despite their fundamental importance, the molecular mechanisms governing how CNCCs interpret developmental signals and coordinate their migration, proliferation, and differentiation to construct the craniofacial skeleton remain incompletely understood.
Our laboratory seeks to uncover these fundamental mechanisms by investigating how primary cilia regulate CNCC behavior and craniofacial skeletal development. By combining sophisticated mouse genetic models with advanced imaging technologies and human stem cell-based approaches, we aim to define how ciliary signaling coordinates the cellular and molecular events that shape the developing face. Ultimately, our work seeks to establish a mechanistic link between ciliary dysfunction and craniofacial disease, providing new insights into the origins of congenital skeletal malformations.
The Pathogenic Link Between Aberrant Ciliogenesis and Ectopic Bone Formation
Bone morphogenetic proteins (BMPs) were originally discovered for their remarkable ability to induce bone formation. Although BMP signaling is now recognized as a central regulator of skeletal development, how it controls cellular fate specification and directs progenitor cells toward the osteogenic lineage remains unclear. Our recent findings point to an intriguing connection between BMP signaling and primary cilia, suggesting that BMP activity may promote ciliogenesis and thereby influence the cellular programs underlying bone formation. This relationship may have important implications for fibrodysplasia ossificans progressiva (FOP), a devastating and currently incurable genetic disorder characterized by progressive formation of bone in soft tissues. FOP is caused by mutations in ACVR1, a BMP type I receptor, that result in aberrant, constitutive activation of BMP signaling and the progressive transformation of normally non-skeletal tissues into bone. We are particularly interested in understanding how dysregulated BMP signaling and altered ciliary function interact to redirect cellular identity and promote pathological osteogenic differentiation.
By uncovering the molecular mechanisms linking BMP signaling, ciliogenesis, and osteogenic cell fate determination, our research aims to reveal previously unrecognized drivers of ectopic bone formation. Ultimately, these discoveries could identify new molecular targets and provide a foundation for developing innovative therapeutic strategies to prevent or limit pathological bone formation in patients with FOP and potentially other skeletal disorders.