Skeletal Development & Regeneration

Research in my lab has a great interest in understanding signaling mechanisms that influence the fate of skeletal progenitors during the development, maintenance, and regeneration of bone tissues.  Ongoing work includes the use of mouse and human embryonic stem cells and induced pluripotent stem (iPS) cells and learning how to direct their differentiation into cells of the axial skeleton.  We also investigate adult bone marrow mesenchymal stem cells (MSCs) and the signaling pathways that influence their fate and function.

Rare Skeletal Diseases

Research in my lab is also interested in different skeletal dysplasia that impact bone tissues. We have become very interested in a rare craniofacial disorder known as cherubism.  Currently, this work is focused on understanding how the Transforming Growth Factor Beta signaling pathway contributes to the pathology of this disease. 

Differentiation of embyronic stem cells and iPS cells into mature skeletal cell types

Understanding how to generate skeletal progenitors from pluripotent stem cells has potentially great value for understanding the molecular basis of skeletal diseases and for the field of regenerative medicine.  Currently, the field is beginning to make real progress in understanding how to differentiate pluripotent stem cells in a very defined way into skeletal progenitors.  However, the cell types generated in vitro are very heterogeneous and their functional validation remains poorly tested. With this in mind, part of our strategy involves genetically engineering mouse and human ES and iPS cells with fluorescent reporters that enable us to visualize and study the biology of distinct skeletal progenitors generated in vitro.  In conjunction with different reporter stem cell lines, we are investigating how different signaling pathways influence the differentiation of pluripotent stem cells into paraxial mesoderm.  We are very interested in how to make paraxial mesoderm cells because they have the potential to give rise to wide breadth of mature skeletal cell types including, osteoblast, chondrocyte, tenocyte, myoblast, and dermal fibroblast.

 Cherubism and Transforming Growth Factor (TGF) Beta Signaling 

Cherubism is a rare autosomal dominant craniofacial disorder affecting pre-pubertal children, which is characterized by multilocular lesions in the mandible and/or maxilla consisting of numerous giant osteoclasts and extensive fibrous-osseous tissue hyperplasia.  Currently, there is no accepted treatment for this disease.  Based on certain characteristics of the cherubism phenotype, we suspected that increased TGFβ signaling may have a key role in the presentation of this disease and have used a mouse model of Cherubism to investigate this possibility.  Our ongoing studies are very encouraging and provide evidence that reducing TGFbeta signaling may be an effective therapuetic approach to treat patients.  

Accepting Lab Rotation Students: Fall 2022 and Spring 2023

Journal Articles