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Research in the Pacifici Laboratory focuses on identifying cellular and molecular mechanisms that regulate the differentiation of progenitor cells into skeletal tissues and permit the assembly of distinct skeletal structures. At the center of the lab’s work are investigations into synovial joint development, heterotopic ossification and fibrodysplasia ossificans progressiva, as well as hereditary multiple exostoses.
While much is known about the structure, composition, and organization of the components of synovial joints, less is understood about how the joints actually form. Pioneering work from the Pacifici Lab has identified a specific subset of progenitor cells – collectively called the interzone – that emerge at each prospective joint formation site in the early fetus and then give rise to the joints.
The lab also has a robust research program into heterotopic ossification and fibrodysplasia ossificans progressive (FOP), two related musculoskeletal disorders that involve the formation of excess skeletal tissue at abnormal anatomical locations. The Pacifici Lab developed a potential therapy for FOP that involves a synthetic, industry-made retinoid agonist. That agonist, Palovarotene, is now in a Phase III clinical trial for FOP patients.
In addition, the lab is investigating hereditary multiple exostoses, also known as multiple osteochondromas, a pediatric skeletal disease characterized by benign cartilaginous tumors that form next to the growth areas of the skeleton in children and young adults. Because of their location, size, and number, the tumors can cause a number of health problems. In some HME patients, they can transform into malignant chondrosarcomas and become life threatening. NIH funding has allowed The Pacifici Lab has created genetic mouse models of the disease, investigating possible mechanisms of tumor formation, long-term fate, behavior, and consequences on the skeleton.
Director of Research, Department of Orthopaedic Surgery
Dr. Pacifici's biomedical research spans three decades and has explored mechanisms of skeletal development and growth in fetal and postnatal life. Specifically, his focus has been on identifying the cellular and molecular mechanisms that regulate the differentiation of progenitor cells and permit assembly of distinct skeletal structures, and on aberrations of these mechanisms in pediatric skeletal disorders.