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Véronique Lefebvre, PhD
Véronique Lefebvre
Investigator

Dr. Lefebvre investigates the genetic mechanisms that generate the diversity of cell types composing the body. Her emphasis is on deciphering how proteins called SOX transcription factors specify stem cells and highly specialized cells in the skeleton, how changes in these factors cause skeletal diseases, and how these factors also control other processes, including brain development and intellectual disability diseases.

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Bio

Since her PhD training, Dr. Lefebvre has dedicated her career to uncovering the 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 establishing the concept that SOX transcription factors specify cell fate and differentiation in virtually all biological processes from development to disease.

She relocated to 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 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.

Education and Training

PhD, Université Catholique de Louvain, Belgium (Biochemistry & Cell Biology), 1990

Fellowship, University of Texas M.D. Anderson Cancer Center (Molecular Genetics), 1997

Titles and Academic Titles

Investigator

Professor

Publication Highlights

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 Sep; 145(14). pii: dev164459. doi: 10.1242/dev.164459
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 Mar; 70(3):371-382. doi: 10.1002/art.40386. PMCID: PMC5826855
Liu CF, Lefebvre V. The transcription factors SOX9 and SOX5/SOX6 cooperate genome‐wide through super‐enhancers to drive chondrogenesis. Nucleic Acids Res. 2015 Nov; 43(17):8183-203. doi: 10.1093/nar/gkv688. PMCID: PMC4787819
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 Dec; 207(5):657-71. doi: 10.1083/jcb.201405098. PMCID: PMC4259807
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 Mar; 22(3):597-609. doi: 10.1016/j.devcel.2011.12.024. PMCID: PMC3306603