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Maurizio Pacifici, PhD
Maurizio Pacifici
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.

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Bio

Dr. Pacifici's research focuses on the identification of cellular and molecular mechanisms that regulate the differentiation of progenitor cells into skeletal tissues and permit the assembly of distinct skeletal structures. The following examples represent ongoing projects:

Synovial joint development: The synovial joints are essential for body motion, normal activities, and quality of life. Much is known about the structure, composition, and organization of their components; however, much less is known about how the joints actually form. Pioneering work from Dr. Pacifici's group 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.

Heterotopic Ossification and Fibrodysplasia Ossificans Progressiva: These two related musculoskeletal disorders involve the formation of excess skeletal tissue at abnormal anatomical locations. HO is caused by severe trauma, burns, and/or immobilization. It can also follow invasive surgeries. FOP is a congenital and extremely aggressive pediatric form of HO. Dr. Pacifici and his colleagues 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.

Hereditary Multiple Exostoses: HME (also known as Multiple Osteochondromas, or MO) is a pediatric skeletal disease characterized by benign cartilaginous tumors (called exostoses or osteochondromas) 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 Dr. Pacifici and his team to create genetic mouse models of the disease, investigate possible mechanisms of tumor formation, long-term fate, behavior, and consequences on the skeleton.

Education and Training

BA, Liceo Scientifico (1969)

PhD, University of Rome School of Medicine, Institute of Histology and Embryology (1974)

Titles and Academic Titles

Director of Research, Department of Orthopaedic Surgery

Dr. Bong S. Lee Endowed Chair in Pediatric Orthopaedics

Professor of Orthopaedic Surgery

Publication Highlights

Billings PC, Yang E, Mundy C, Pacifici M. Domains with highest heparan sulfate-binding affinity reside at opposite ends in BMP2/4 versus BMP5/6/7: implications for function. J. Biol. Chem. 2018 Sep; 293(37):14371-14383. doi: 10.1074/jbc.RA118.003191. PMID: 30082319
Mundy C, Yang E, Takano H, Billings PC, Pacifici M. Heparan sulfate antagonism alters bone morphogenetic protein signaling and receptor dynamics, suggesting a mechanism in Hereditary Multiple Exostoses. J. Biol. Chem. 2018 May; 293(20):7703-7716. doi: 10.1074/jbc.RA117.000264. Epub 2018 Apr 5. PMID: 29622677
Decker RS, Um H-B, Dyment NA, Cottinham N, Usami Y, Enomoto-Iwamoto M, Kronenberg MS, Rowe DW, Koyama E, Pacifici M. Cell origin, volume and arrangement are drivers of articular cartilage formation, morphogenesis and response to injury in mouse limbs. Dev. Biol. 2017 Jun; 426(1):56-68. doi: 10.1016/j.ydbio.2017.04.006. Epub 2017 Apr 21. PMID: 28438606
Sinha S, Mundy C, Bechtold T, Sgariglia F, Ibrahim MM, Billings PC, Carroll K, Koyama E, Jones KB, Pacifici M. Unsuspected osteochondroma-like outgrowths in the cranial base of Hereditary Multiple Exostoses patients and modeling and treatment with a BMP antagonist in mice. PLOS Genet. 2017 Apr; 13(4):e1006742. doi: 10.1371/journal.pgen.1006742. PMID: 28445472
Huegel J, Enomoto-Iwamoto M, Sgariglia F, Koyama E, Pacifici M. Heparanase stimulates chondrogenesis and is upregulated in human ectopic cartilage: A mechanism possibly involved in Hereditary Multiple Exostoses. Am. J. Pathol. 2015 Jun; 185(6):1676-85. doi: 10.1016/j.ajpath.2015.02.014. Epub 2015 Apr 8. PMID: 25863260