Beier Lab

Research

Skeletal development is a complex process that involves interactions between multiple cell types and is regulated by numerous genetic and environmental factors. Deregulation of any of these factors can lead to serious pathologies such as various forms of dwarfism (e.g. chondrodysplasias). Moreover, improper skeletal development is directly linked to diseases of the adult skeleton such as osteoarthritis.

The majority of our skeleton forms through the process of endochondral ossification in which the later bone is first laid down as a cartilage model. The cells of the cartilage, the chondrocytes, control the length, shape and function of endochondral bones. Our lab is interested in the signaling pathways and molecular mechanisms that regulate the biology of chondrocytes and other skeletal cells. In this context, we follow three overlapping areas of research.

One focus of the lab is the role of intracellular signaling pathways in chondrocytes during development, aging and skeletal diseases. We have demonstrated important functions for Rho GTPases and several kinase families in the control of chondrocyte biology. Current projects address the function of selected signaling molecules in cartilage in vivo and the elucidation of their mechanisms of action (such as effects on gene expression). We are especially interested in the interactions of chondrocytes with other cell types, including osteoblasts and osteoclasts. We utilize tissue-specific knockout mice, organ and cell cultures coupled to a large variety of molecular and cellular assays in these studies.

A second line of investigation addresses the roles of transcriptional regulators of chondrocyte differentiation. In particular, we are interested in multiple members of the nuclear receptor family. We use genetically altered mice in conjunction with genomic (microarrays, RNA Seq, ChIP Seq) approaches to identify the roles and target genes of these transcription factors in skeletal development. More recently, we have expanded these studies to explore epigenetic mechanisms involved in cartilage gene expression.

Our third area of interest are the molecular mechanisms involved in the progression of osteoarthritis. We have identified several pathways (such as TGFalpha-EGFR signaling) that possible contribute to osteoarthritis. We are now testing the function of some of these pathways using genetic and surgical models of osteoarthritis, together with cell and organ culture and biochemical techniques. In particular, we are testing whether drugs that modulate activity of these pathways present suitable approaches to halt or slow osteoarthritis progression in animal models.