Claire Shea

Biography

Claire joined the group in September 2013.  She previously studied at Northwestern University in the United States (B.A., with Honors, Biological Sciences, 2011) and the University of Geneva in Switzerland (M.S. Biology, 2013), and was a 2011 Fulbright Fellow at the University of Geneva.  During her undergraduate degree, she worked in the laboratory of Dr. Andrew Dudley, studying the adherent properties of Piga mutant cartilage cells and the genetic expression of post-natal secondary cartilage in mice.  In Geneva, she worked with Dr. Juan Montoya-Burgos on design of novel gene-capture techniques and the study of exoskeletal development in fast-evolving, neo-tropical armoured catfish.   
Her current research interests centre on the mechanostimulation of the developing skeleton.  She is interested in mechanisms of cell signalling and patterning during embryogenesis, and practical application of developmental biology to bioengineering therapeutics. 

Project Title
Mechanical Regulation of Skeletal Development: From Embryonic Development to Regenerative Therapies

Project Description
The construction of the human skeleton has evolved to provide the body with support and protection and to facilitate movement. Understanding how a healthy skeleton is formed during embryonic development is important for avoidance and treatment of diseases such as osteoporosis and osteoarthritis. Moreover, the aspiration to use stem cells for skeletal regenerative therapies is dependent on our ability to guide complete cellular maturation into robust functional tissues. Interdisciplinary work previously conducted by the Murphy lab modelled how mechanical forces impact developing tissues, and showed that movement of the embryo in the uterus is necessary for normal skeletal development.  In chick and mouse which are unable to experience embryonic muscle contractions (kicking), bone development is delayed or abnormal and joints fail to form.   More recent work has determined which genes are differentially expressed when the mechanical environment of mouse limbs is altered.  This revealed a potential role for the Wnt cell-signaling pathway, known to be vital to embryonic patterning, in mechanotransduction during crucial stages of skeletal development.  Claire’s work will be focused on characterizing expression patterns of Wnt component genes during limb development, in both normal and mechanically altered animals, to assess how molecular mechanisms of the Wnt pathway are controlled by physical stimuli.     

Appropriate mechanical stimulation has long been known to be important to repair and maintenance of adult skeletal tissues (for example, in healing of fractures in weight-bearing bones or prevention of bone mass loss in astronauts during weightlessness).  This has resulted in widespread interest for incorporation of mechanical stimuli into regimes for regenerating skeletal tissues from progenitor cells, particularly for the production of cartilage for joint repair.  However, efforts to regenerate cartilage have been hampered by tissue instability.  We hope to help design more controlled regimes for tissue engineering by studying how mechanical stimuli influence molecular signaling to guide stable cartilage production during normal embryonic development.  The ability to reproduce stable cartilage production from stem cells in vitro would provide minimally invasive, less-traumatic therapeutic options for the treatment of common skeletal diseases such as osteoporosis and osteoarthritis.