Research Interests
Craniofacial development and growth, Bone, Cartilage and Bone Development, Degenerative Diseases (Osteoarthritis) and Repair, Tooth development, Mineralization, Periodontal Anomalies, Development and Remodeling of Sutures and Ligaments
Research Focus Teams
Rare Disease, Oral Health, Arthritis
Departments
Oral Biological and Medical Sciences
Contact
Email: daniel.graf@ubc.ca
Office Phone:
Publications
Daniel Graf graduated in Biology/Biochemistry from the Swiss Federal School of Technology (ETH) Zurich. He did his PhD (ETH Zurich) at the Robert Koch-Institute, Berlin and post-doctoral studies at the MRC Clinical Sciences Centre, London (UK), and Biomedical Sciences Research Centre ‘Al. Fleming’, Athens, Greece. He led research groups at the BSRC ‘Al. Fleming’ Athens, the Institute of Oral Biology, University of Zurich, the School of Dentistry at the University of Alberta. He joined UBC to direct the Craniofacial, Oral, Dental Disorders (CODED) research cluster of the Faculty of Dentistry in fall 2023.
Trained in molecular and experimental Immunology, Developmental Biology, and Mouse Genetics he has been focusing on the molecular analysis of Bone Morphogenetic Protein (BMP) signaling through functional genomics approaches. He studied BMP function in tissues other than bone, including the immune system and the brain, but more recently focused on craniofacial tissues, cartilage, and sutures. His lab has extensive experience in the use of genetic mouse models, disease models, microCT live imaging and image analysis including segmentation, volume determination and analysis of bone parameters. His lab has also strong expertise in tissue histology and immunohistochemistry, analysis of gene expression, in vitro culture systems, in particular for cartilage and bone differentiation.
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.
Project 1: 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)
Project 2: 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).
Project 3: 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.