Stem Cells in Craniofacial Tissues

One of the fundamental questions in biology is how tissues are maintained throughout life when most mature functional cells survive only for limited periods. Adult stem cells are thought to solve this challenge by self-renewing and continuously generating new cells, thereby maintaining tissue homeostasis and enabling regeneration after injury. Understanding how these long-lived stem cells are established, maintained, and activated during repair is central to our research program.

A major focus of our laboratory is the identification and characterization of adult stem cells in craniofacial tissues. We have discovered endogenous stem cell populations in the cranial sutures, dental pulp, and salivary gland ducts that contribute to tissue maintenance and regeneration (Nature Communications, 2016; Cell Reports, 2018; Journal of Dental Research, 2026). Using state-of-the-art mouse genetics, lineage tracing, and computational approaches, we have further defined molecular mechanisms that regulate stem cell fate decisions, self-renewal, and differentiation (JBMR, 2017; Science Translational Medicine, 2021; Science Advances, 2022).

Our current research focuses on mandibular condylar cartilage stem cells, a unique stem cell population that is essential for temporomandibular joint growth, maintenance, and regeneration. Through genetic and molecular studies, we seek to understand how these cells contribute to TMJ homeostasis and how their dysfunction leads to degenerative joint disease. These works are supported by an NIH/NIDCR R01 and R21 awards.

Non-coding RNA and Stem Cell Regulation

In addition to identifying stem cell populations, we seek to understand the molecular mechanisms that regulate their behavior. One major focus of our laboratory is the role of non-coding RNAs in stem cell maintenance, differentiation, and tissue regeneration.

Although only 2–3% of the human genome encodes proteins, more than 70% of the genome is actively transcribed into non-coding RNAs with important regulatory functions. Our laboratory investigates how non-coding RNAs regulate stem cell fate, tissue homeostasis, and regeneration. Using genetic mouse models, transcriptomic analyses, and functional studies, we seek to identify non-coding RNA networks that control craniofacial stem cell behavior and skeletal regeneration.

Our research demonstrated that deletion of microRNA-27a (Mir27a), a small non-coding RNA, results in severe osteoporotic bone loss in young mice, revealing an essential role for Mir27a in skeletal homeostasis (eLife, 2023). Building upon these findings, we are currently identifying and characterizing non-coding RNAs that regulate stem cell populations responsible for temporomandibular joint maintenance and regeneration. Through these studies, we aim to uncover novel regulatory mechanisms that can be harnessed to promote tissue regeneration and treat craniofacial diseases. These works are supported by an NIH/NIDCR R01 and R21 awards.