Welcome to Shore/Kaplan Laboratory
Our research investigates rare genetic disorders of heterotopic ossification. Heterotopic ossification is the formation of bone in the wrong place at the wrong time – cartilage and bone develop within soft connective tissues such as skeletal muscle and adipose tissue. Our work has demonstrated that these are disorders of mis-regulation of stem cell differentiation and loss of post-natal tissue maintenance that leads to aberrant formation of extra-skeletal bone and cartilage. We identified activating mutations in the ACVR1 gene as the cause of fibrodysplasia ossificans progressiva (FOP) and inactivating mutations in GNAS as the cause of progressive osseous heteroplasia (POH). Our ongoing work explores the cellular and molecular basis of the dysregulated cell differentiation and bone tissue formation in these conditions using in vitro and in vivo models in order to understand the consequences of the mutations and to identify and test therapeutic strategies.
Our Mission --
-- to understand the cell and molecular mechanisms that regulate cell fate decisions in FOP and POH, to identify the effects of the underlying gene mutations and altered signaling pathways on the skeleton and other tissues/organs in the body, and to identify therapeutic targets in order to improve the health and well-being of the people and their families who live with these conditions.
The Shore Lab, as part of the Center for Research in FOP and Related Disorders and in collaboration with Dr. Frederick Kaplan, investigates the genetic regulation of cell development and differentiation through studies of extra-skeletal (heterotopic) bone formation in two rare genetic diseases, fibrodysplasia ossificans progressiva (FOP) and progressive osseous heteroplasia (POH). While several features distinguish POH from FOP, both of these disorders induce ectopic bone formation during early childhood and are progressive throughout life, forming bone in soft tissues such as skeletal muscle. By identifying the underlying genetic mutations that cause these diseases, we uncovered key regulatory proteins and cell signaling pathways that determine where and when bone forms.To investigate the cellular and molecular mechanisms of cartilage and bone formation and to identify treatment strategies and conduct pre-clinical drug testing, we develop, characterize, and apply in vitro cell assays and in vivo mouse and zebrafish systems. On-going work includes investigating the stem cells that are mis-directed to form bone along with their interactions with other cells and tissues that influence and permit extra-skeletal bone formation, including the tissue microenvironment, biomechanical signaling, and the immune system.Our work, which began when few knew of FOP, POH, and heterotopic ossification or appreciated the value of understanding rare diseases, has stimulated an active and expanding field of basic research and translational application.
If you are a postdoc or graduate student who is interested in working with us, please contact Eileen Shore (email@example.com) to discuss your interests and learn more about us. Opportunities are currently available in several research areas.