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Faculty Information

Shoshana Yakar, Ph.D.
Associate Professor
Basic Science and Craniofacial Biology
Room 901E Dental Center, 421 First Avenue
E-mail:

 

Education:

1990 B.S., Tel-aviv University

1992 Ms.C.,  Tel-aviv University

1996 Ph.D., Tel-aviv University

1996-2001 Post-Doc training, NIDDK, NIH 

 

Research Interests / Professional Overview:

 

A major focus of my work has been on understanding the role(s) of insulin-like growth factors (IGF's) in tissue growth, development and repair. In particular, this work has dealt with the question of distinguishing paracrine effects of locally produced IGF from endocrine effects of circulating IGF synthesized primarily by the liver.  Initially, I used the Cre-LoxP system to develop a liver-specific IGF-1 gene deleted (LID) mouse model, and characterized its phenotype with respect to metabolism, skeletal growth and tumor progression. I subsequently used a similar approach to assess the roles of IGF binding proteins in regulating IGF-1 bioavailability and activity.

I have continued this work, now directed primarily at understanding the effects of IGF-1 on the skeleton, studies funded by two NIH awards: NIAMS: RO1-AR054919-01,NIAMS: RO1-AR055141-01.  Our ongoing investigation identifies bone compartments affected by serum/tissue IGF-1, bone cellular population affected by serum/tissue IGF-1 deficiency and determines the mechanism, by which serum/tissue IGF-1 modulates skeletal integrity.  

We use state of the art technologies to achieve our goals including: E-Coli-based technology to generate knockout, knock-in or transgenic mice, micro CT for analysis of skeletal morphology, histomorphometry for analysis of skeletal cellular population, and a few other molecular biology techniques aimed at understanding gene regulation in bone cells.  Outcomes of our studies add significant information on the relationship between serum/tissue IGF-1 and bone mineral density, and we believe they will affect future treatments for musculoskeletal abnormalities.

 

 

Current Funding:

1R01AR054919-01A1- NIH/NIAMS, 2007-2012

1R01AR055141-01 NIH/NIAMS, 2008-2013 

 

Pub Med Articles:

106

 

Representative Publications:

1: Courtland HW, Kennedy OD, Wu Y, Gao Y, Sun H, Schaffler MB, Yakar S. Low levels of plasma IGF-1 inhibit intracortical bone remodeling during aging. Age (Dordr). 2012 Sep 14. [Epub ahead of print] PubMed PMID: 22976122.   
2: Elis S, Wu Y, Courtland HW, Sun H, Rosen CJ, Adamo ML, Yakar S. Increased serum IGF-1 levels protect the musculoskeletal system but are associated with elevated oxidative stress markers and increased mortality independent of tissue igf1 gene expression. Aging Cell. 2011 Jun;10(3):547-50. doi: 10.1111/j.1474-9726.2011.00683.x. Epub 2011 Mar 22. PubMed PMID: 21418509; PubMed Central PMCID: PMC3094487.   
3: Courtland HW, Sun H, Beth-On M, Wu Y, Elis S, Rosen CJ, Yakar S. Growth hormone mediates pubertal skeletal development independent of hepatic IGF-1 production. J Bone Miner Res. 2011 Apr;26(4):761-8. doi: 10.1002/jbmr.265. PubMed PMID: 20928887; PubMed Central PMCID: PMC3179330.   
4: Yakar S, Courtland HW, Clemmons D. IGF-1 and bone: New discoveries from mouse  models. J Bone Miner Res. 2010 Dec;25(12):2543-52. doi: 10.1002/jbmr.234. Review. Erratum in: J Bone Miner Res. 2011 Feb;26(2):439. PubMed PMID: 20836088; PubMed Central PMCID: PMC3179280.   
5: Courtland HW, DeMambro V, Maynard J, Sun H, Elis S, Rosen C, Yakar S. Sex-specific regulation of body size and bone slenderness by the acid labile subunit. J Bone Miner Res. 2010 Sep;25(9):2059-68. doi: 10.1002/jbmr.94. PubMed PMID: 20499371; PubMed Central PMCID: PMC3118255.   
6: Elis S, Courtland HW, Wu Y, Fritton JC, Sun H, Rosen CJ, Yakar S. Elevated serum IGF-1 levels synergize PTH action on the skeleton only when the tissue IGF-1 axis is intact. J Bone Miner Res. 2010 Sep;25(9):2051-8. doi: 10.1002/jbmr.100. PubMed PMID: 20499370; PubMed Central PMCID: PMC3118256.   
7: Elis S, Courtland HW, Wu Y, Rosen CJ, Sun H, Jepsen KJ, Majeska RJ, Yakar S. Elevated serum levels of IGF-1 are sufficient to establish normal body size and skeletal properties even in the absence of tissue IGF-1. J Bone Miner Res. 2010 Jun;25(6):1257-66. doi: 10.1002/jbmr.20. PubMed PMID: 20200935; PubMed Central PMCID: PMC3153133.   
8: Fierz Y, Novosyadlyy R, Vijayakumar A, Yakar S, LeRoith D. Insulin-sensitizing therapy attenuates type 2 diabetes-mediated mammary tumor progression. Diabetes.  2010 Mar;59(3):686-93. doi: 10.2337/db09-1291. Epub 2009 Dec 3. PubMed PMID: 19959755; PubMed Central PMCID: PMC2828655.   
9: Menagh PJ, Turner RT, Jump DB, Wong CP, Lowry MB, Yakar S, Rosen CJ, Iwaniec UT. Growth hormone regulates the balance between bone formation and bone marrow adiposity. J Bone Miner Res. 2010 Apr;25(4):757-68. doi: 10.1359/jbmr.091015. PubMed PMID: 19821771; PubMed Central PMCID: PMC3153330.   
10: Fritton JC, Emerton KB, Sun H, Kawashima Y, Mejia W, Wu Y, Rosen CJ, Panus D, Bouxsein M, Majeska RJ, Schaffler MB, Yakar S. Growth hormone protects against ovariectomy-induced bone loss in states of low circulating insulin-like growth factor (IGF-1). J Bone Miner Res. 2010 Feb;25(2):235-46. doi: 10.1359/jbmr.090723. PubMed PMID: 19619004; PubMed Central PMCID: PMC3153382.   
11: Yakar S, Canalis E, Sun H, Mejia W, Kawashima Y, Nasser P, Courtland HW, Williams V, Bouxsein M, Rosen C, Jepsen KJ. Serum IGF-1 determines skeletal strength by regulating subperiosteal expansion and trait interactions. J Bone Miner Res. 2009 Aug;24(8):1481-92. doi: 10.1359/jbmr.090226. PubMed PMID: 19257833; PubMed Central PMCID: PMC2718800.   
12: Kawashima Y, Fritton JC, Yakar S, Epstein S, Schaffler MB, Jepsen KJ, LeRoith D. Type 2 diabetic mice demonstrate slender long bones with increased fragility secondary to increased osteoclastogenesis. Bone. 2009 Apr;44(4):648-55. doi: 10.1016/j.bone.2008.12.012. Epub 2008 Dec 24. PubMed PMID: 19150422; PubMed Central PMCID: PMC2659558.