Professor of Orthopedic Surgery at University of Pennsylvania
Translational Research Program in Pediatric Orthopaedics
Developmental Biology Research Affinity Group (CHOP)
Penn Center for Musculoskeletal Disorders (PCMD)
Penn Institute for Regenerative Medicine (Penn IRM)
Penn Skin Biology and Diseases Resource-based Center (Penn SBDRC)
Dr. Lefebvre has dedicated her career since her PhD training to uncovering genetic mechanisms whereby stem cells and differentiated cells acquire their identity and execute specialized activities. During postdoctoral training at the University of Texas, she helped discover that the SOX9 transcription factor is a master regulator of cartilage cells. In establishing her laboratory at the Cleveland Clinic Lerner Research Institute, she broadened her research scope and discovered important roles for several other SOX proteins in the skeletal system, namely SOX5 and SOX6, which assist SOX9 in cartilage cells, and SOX4 and SOX11, which pivotally control skeletal stem/progenitor cells. Providing expertise well beyond skeletal research, Dr. Lefebvre significantly contributed to establish the concept that SOX transcription factors specify cell fate and differentiation in virtually all biological processes from development to disease. She relocated to the Children’s Hospital of Philadelphia in July of 2018, where she further explores the actions and regulation of SOX proteins in the skeleton and brain. Fundamental research projects on normal development and adulthood provide instrumental information that is directly used in translational projects on rare skeletal malformation and intellectual disability diseases, and prevalent adult-onset diseases, including osteoarthritis and osteoporosis. Dr. Lefebvre has published in high-impact scientific journals and received invitations to speak at prestigious conferences worldwide. She has been continuously supported by grants from the National Institutes of Health and research foundations, and regularly serves on study sections for the like. Additional community services include the chairing of conferences, such as the 2014 International SOX Research Conference and 2015 Gordon Research Conference on Cartilage Biology and Pathology. Last but not least, she is a strong believer that career success is measured not merely by independent research accomplishments but most effectively and most gratifyingly by multi-team collaborations and by mentoring new generations of research and clinician scientists.
Ph.D., Université Catholique de Louvain, Louvain-la-Neuve, Belgium (Biochemistry & Cell Biology), 1990
Postdoctoral Fellowship, University of Texas M.D. Anderson Cancer Center, Houston, TX (Molecular Genetics), 1992-1997
Dy P, Wang W, Bhattaram P, Wang Q, Wang L, Ballock RT, Lefebvre V. Sox9 directs hypertrophic maturation and blocks osteoblast differentiation or growth plate chondrocytes. Dev Cell. 2012;22: 597–609. PMCID: PMC3306603.
Bhattaram P, Penzo-Méndez A, Kato K, Bandyopadhyay K, Gadi A, Taketo MM, Lefebvre V. SOXC proteins amplify canonical WNT signaling to secure non-chondrocytic cell fates in skeletogenesis. J Cell Biol. 2014;207: 657-671. PMCID: PMC4259807.
Liu CF, Lefebvre V. The transcription factors SOX9 and SOX5/SOX6 cooperate genome‐wide through super‐enhancers to drive chondrogenesis. Nucleic Acids Res. 2015;43: 8183-8203. PMCID: PMC4787819.
Bhattaram P, Muschler G, Wixler V, Lefebvre V. Inflammatory cytokines stabilize SOXC transcription factors to mediate the transformation of fibroblast-like synoviocytes in arthritic disease. Arthritis Rheumatol. (2018);70: 371-382. PMCID: PMC5826855.
Liu CF, Angelozzi M, Haseeb A, Lefebvre V. SOX9 is dispensable for the initiation of epigenetic remodeling and the activation of marker genes at the onset of chondrogenesis. Development. 2018;145(14). PMCID: PMC6078338.