Daniel Graf

My lab uses craniofacial development (development of skull bones, cartilage, and teeth) to study how cell-cell interactions regulate cell- and tissue differentiation, and how dysregulation of these processes leads to congenital abnormalities. About 3 out of 4 congenital birth defects have craniofacial involvement. Thus, my research not only has foundational impact, it helps to improve clinical understanding of craniofacial disorders and helps improving applications in tissue engineering. An example for this is our work on cellular processes that cause midfacial hypoplasia and upper airway obstruction that led to collaborations with clinicians on sleep disordered breathing or the etiology and treatment of osteoarthritis.

Making a head: connecting reciprocal signaling to cell reprogramming

The vertebrate head has the amazing capacity to adapt its shape and functionalities to habitats and ecological niches. Central to this are cranial neural crest cells (CNC), which are key contributors to the most variable structures of the head: the facial bones, cartilages, and teeth. A handful of evolutionary conserved, reiteratively used extracellular signaling pathways control development of most facial structures. The same pathways are also major contributors to facial shape variation. How is this achieved? We use various genetic and molecular approaches to address this question. Supported by NSERC Discovery Grant)

Osteoarthritis as consequence of endogenous changes to cartilage homeostasis and repair: linking cartilage differentiation to cartilage degradation

Osteoarthritis (OA) is a debilitating, progressive disease affecting cartilaginous tissues, such as the knees and spine. Long considered a wear-and-tear disease due to lack of intrinsic repair, it is now clear that articular cartilage undergoes constant albeit slow renewal, in part driven by subchondral skeletal stem cells. The signals that direct stem cells to produce hyaline cartilage are not well understood. Cartilage repair following microfractures to treat small cartilage defects typically leads to formation of less resilient and shorter-lived fibrocartilage. Understanding how cartilage properties are controlled and how inappropriate properties predispose to OA may hold the key for clinical regeneration of hyaline cartilage and thus a potential cure for OA. We use predominantly Bmp-based mutant mouse models to describe OA development starting with progenitor cells ending with late-stage OA, and translate these findings to human OA and cartilage repair. Supported by CIHR Project grant).

Integration of mechanosensation, cell signaling, and cell differentiation in sutures and ligamentous structures

Cranial sutures and ligaments are dynamic structures in which stem cell biology, bone formation, and mechanical forces interface, influencing the shape of the skull or attachment of teeth, ligaments, and joints throughout development and beyond. We study the role of key molecules important for the development and function of these various structures to understand their formation, remodeling, and regeneration.