Positions
- Professor
-
Orthopedic Surgery
Baylor College of Medicine
Houston, TX US
- Professor
-
Molecular and Human Genetics
Baylor College of Medicine
- Associate Director
-
Center for Skeletal Medicine and Biology
Baylor College of Medicine
- Adjunct Associate Professor
-
Department of Medicine
Vanderbilt University
- Member
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Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas United States
Education
- Postdoctoral Fellowship at Baylor College of Medicine
- 01/2004 - Houston, Texas United States
- Molecular and Human Genetics
- PhD from Claude Bernard University
- 12/1999 - Lyon, France
Professional Interests
- Mechanisms of bone development, remodeling, repair and cancer cell metastasis
Professional Statement
Our research aims at understanding how the skeleton forms, grows, mineralizes, ages, repairs and communicates with other tissues in health and diseases.One main focus of the laboratory is on the etiology of the skeletal maladies observed in individuals with neurofibromatosis type I (NF1). We are particularly interested in the fracture non-union and dystrophic scoliosis observed in some of these patients. We use genetic and pharmacological strategies to identify both cells of origin and molecular abnormalities causing these orthopedic conditions, with the goal of designing and testing novel targeted therapeutic strategies to improve bone mass, bone strength and bone repair in children with NF1. These studies also provide critical insights into the role of neurofibromin, the RAS-GAP protein encoded by the NF1 gene, in endochondral bone formation, remodeling, repair and mineralization.
A second focus area of the laboratory is related to the interaction between the autonomic nervous system and bone cells. Our current emphasis is on determining the role of the endogenous sympathetic and parasympathetic nervous systems in the regulation of bone homeostasis, and on addressing the biological and clinical relevance of these preclinical findings. This leads us to study the role of the norepinephrine transporter and conditions including bone aging, depression and Alzheimer’s disease and their impact on bone remodeling.
A third active line of research in the laboratory revolves around the biology of chondrocytes, the cells of cartilaginous tissues that allow bone elongation during the development and protection of joint articular surfaces in adults. Through our focus on the transcription factor TonEBP/Nfat5, we investigate how chondrocytes survive and function in their hyperosmotic, avascular and low nutrient environment.
Websites
Selected Publications
- Couasnay G, Madel MB, Lim J, Lee B, Elefteriou F "Sites of Cre-recombinase activity in mouse lines targeting skeletal cells.." J Bone Miner Res.2021;:
- Ma Y, Gross AM, Dombi E, (...), Widemann BC, Rios JJ, Elefteriou F "A molecular basis for neurofibroma-associated skeletal manifestations in NF1.." Genet Med..2020;22:1786-1793. Pubmed PMID: 32601387
- Ma Y, Elefteriou F "Brain-Derived Acetylcholine Maintains Peak Bone Mass in Adult Female Mice.." J Bone Miner Res.2020;35:1562-1571. Pubmed PMID: 32282950
- Zhu Y, Ma Y, Elefteriou F "Cortical bone is an extraneuronal site of norepinephrine uptake in adult mice.." Bone Rep..2018;9:188-198. Pubmed PMID: 30581894
- Elefteriou F "Impact of the Autonomic Nervous System on the Skeleton.." Physiol Rev. 2018 98 : 1083-1112. Pubmed PMID: 29717928
- Mulcrone PL, Campbell JP, Clément-Demange L, Anbinder AL, Merkel AR, Brekken RA, Sterling JA, Elefteriou F "Skeletal Colonization by Breast Cancer Cells Is Stimulated by an Osteoblast and b2AR-Dependent Neo-Angiogenic Switch.." J Bone Miner Res.. 2017 32 : 1442-1454. Pubmed PMID: 28300321
- Vignaux G, Ndong JD, Perrien DS, Elefteriou F "Inner Ear Vestibular Signals Regulate Bone Remodeling via the Sympathetic Nervous System." J Bone Miner Res. 2015 June ; 30 (6): 1103-11. Pubmed PMID: 25491117
- Karolak MR, Yang X, Elefteriou F "FGFR1 signaling in hypertrophic chondrocytes is attenuated by the Ras-GAP neurofibromin during endochondral bone formation." Hum Mol Genet. 2015 May 1; 24 (9): 2552-64. Pubmed PMID: 25616962
- de la Croix Ndong J, Makowski AJ, Uppuganti S, Vignaux G, Ono K, Perrien DS, Joubert S, Baglio SR, Granchi D, Stevenson DA, Rios JJ, Nyman JS, Elefteriou F "Asfotase-α improves bone growth, mineralization and strength in mouse models of neurofibromatosis type-1." Nat Med. 2014 August ; 20 (8): 904-10. Pubmed PMID: 24997609
- Ma Y, Krueger JJ, Redmon SN, Uppuganti S, Nyman JS, Hahn MK, Elefteriou F "Extracellular norepinephrine clearance by the norepinephrine transporter is required for skeletal homeostasis." J Biol Chem. 2013 October 18; 288 (42): 30105-13. Pubmed PMID: 24005671
- Ono K, Karolak MR, Ndong Jde L, Wang W, Yang X, Elefteriou F "The ras-GTPase activity of neurofibromin restrains ERK-dependent FGFR signaling during endochondral bone formation." Hum Mol Genet. 2013 August 1; 22 (15): 3048-62. Pubmed PMID: 23571107
- Stevenson DA, Little D, Armstrong L, Crawford AH, Eastwood D, Friedman JM, Greggi T, Gutierrez G, Hunter-Schaedle K, Kendler DL, Kolanczyk M, Monsell F, Oetgen M, Richards BS, Schindeler A, Schorry EK, Wilkes D, Viskochil DH, Yang FC, Elefteriou F "Approaches to treating NF1 tibial pseudarthrosis: consensus from the Children's Tumor Foundation NF1 Bone Abnormalities Consortium." J Pediatr Orthop. 2013 April ; 33 (3): 269-75. Pubmed PMID: 23482262
- Campbell JP, Karolak MR, Ma Y, Perrien DS, Masood-Campbell SK, Penner NL, Munoz SA, Zijlstra A, Yang X, Sterling JA, Elefteriou F "Stimulation of host bone marrow stromal cells by sympathetic nerves promotes breast cancer bone metastasis in mice." PLoS Biol. 2012 July ; 10 (7): e1001363. Pubmed PMID: 22815651
- Wang W, Nyman JS, Ono K, Stevenson DA, Yang X, Elefteriou F "Mice lacking Nf1 in osteochondroprogenitor cells display skeletal dysplasia similar to patients with neurofibromatosis type I." Hum Mol Genet. 2011 October 15; 20 (20): 3910-24. Pubmed PMID: 21757497
- Patel MS, Elefteriou F "The new field of neuroskeletal biology." Calcif Tissue Int. 2007 May ; 80 (5): 337-47. Pubmed PMID: 17440766
- Elefteriou F, Ahn JD, Takeda S, Starbuck M, Yang X, Liu X, Kondo H, Richards WG, Bannon TW, Noda M, Clement K, Vaisse C, Karsenty G "Leptin regulation of bone resorption by the sympathetic nervous system and CART." Nature. 2005 March 24; 434 (7032): 514-20. Pubmed PMID: 15724149
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