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Archana Sanjay, PhD
Assistant Professor, Anatomy and Cell Biology
Assistant Professor, Sol Sherry Thrombosis Research Center
Telephone: 215-707- 3384
Fax: 215-707-2966
Email: asanjay@temple.edu
Department of Anatomy and Cell Biology
Sol Sherry Thrombosis Research Center
Jiwaji University, Gwalior, India
B.Sc., Biology, 1985
Devi Ahilya University, Indore, India
M.Sc.,
Biochemistry,
1987
Bombay University, India
Ph.D ,
Biochemistry,
1994
NYU Medical Center, New York, NY
Post Doctoral Fellow ,
1994-1996
Yale University School of Medicine, New Haven, CT
Postdoctoral Associate ,
1997-1998
Yale University School of Medicine, New Haven, CT
Postdoctoral Fellow,
1998-2001
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Bone is a rigid yet dynamic organ that is continuously molded, shaped and repaired. Once formed, bone undergoes a remodeling process that involves bone-resorption by osteoclasts and bone formation by osteoblasts. Bone remodeling imbalances result in skeletal diseases such as osteoporosis, rheumatoid arthritis and metastatic cancers. Bone remodeling is a complex process involving two cell types, several signaling pathways and multitude of proteins. The focus of my lab is to elucidate the molecular mechanisms that regulate both bone resorption and bone formation. We are elucidating the role of non-receptor tyrosine kinase Src in the signal transduction mechanism(s) in osteoclasts and osteoblasts.
Tyrosine kinase Src’s involvement in bone biology stems from three observations; 1) bone histomorphometric analysis of long bones of the Src knock out mice shows decreased bone resorption is and increased bone formation; 2) the cellular defect induced by Src deletion are cell autonomous and 3) other Src family tyrosine kinases that are expressed either in osteoclast or osteoblast cannot compensate for absence of Src protein suggesting that Src kinase plays a unique role in bone biology.
Our focus, therefore, is to examine the role of Src in signal transduction mechanisms in bone cells as well as developing the necessary tools to realize this endeavor.
The projects currently undertaken in the lab include:
1) Evaluation of the contributions of Src domains in both bone formation and resorption
2) Analysis of the role of Src–associated protein
3) Identification novel proteins that bind to Src domains
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Chapters and Reviews
Sanjay A. and Baron R .The role of Src, Cbl and Pyk2 in vitronectin receptor-mediated adhesion in osteoclasts. In Molecular Biology of Orhtopaedics, Published by AAOS, Rosier, R and Evans C.H., Editors, Section V, p 221-228(2002)
Sanjay, A., Horne W C and Baron R. The Cbl family: Ubiquitin ligases regulating signaling by tyrosine kinases. Science STKE (2001), http://www.stke.org/cgi/content/full OC_sigtrans; 2001/110/pe40
Duong L.T., Sanjay A., Horne W.C., Baron R. and Rodan G. Integrin and calcitonin receptor signaling in the regulation of the cytoskeleton and function of the osteoclast. In Principles of Bone Biology, Bilezikian J., Raisz L. and Rodan G. Editors, Vol. I, Chapter 9, p 141-150, 2002.
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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)
19587372. Chari R, Kim S, Murugappan S, Sanjay A, Daniel JL, Kunapuli SP, Lyn, PKC-delta, SHIP-1 interactions regulate GPVI-mediated platelet-dense granule secretion. Blood 114:14(3056-63)2009 Oct 1
19257814. Nakajima A, Sanjay A, Chiusaroli R, Adapala NS, Neff L, Itzsteink C, Horne WC, Baron R, Loss of Cbl-b increases osteoclast bone-resorbing activity and induces osteopenia. J Bone Miner Res 24:7(1162-72)2009 Jul
18314002. Arnott JA, Zhang X, Sanjay A, Owen TA, Smock SL, Rehman S, DeLong WG, Safadi FF, Popoff SN, Molecular requirements for induction of CTGF expression by TGF-beta1 in primary osteoblasts. Bone 42:5(871-85)2008 May
18180404. Nakashima H, Frank GD, Shirai H, Hinoki A, Higuchi S, Ohtsu H, Eguchi K, Sanjay A, Reyland ME, Dempsey PJ, Inagami T, Eguchi S, Novel role of protein kinase C-delta Tyr 311 phosphorylation in vascular smooth muscle cell hypertrophy by angiotensin II. Hypertension 51:2(232-8)2008 Feb
17978100. Destaing O, Sanjay A, Itzstein C, Horne WC, Toomre D, De Camilli P, Baron R, The tyrosine kinase activity of c-Src regulates actin dynamics and organization of podosomes in osteoclasts. Mol Biol Cell 19:1(394-404)2008 Jan
17921256. Li L, Hisamoto K, Kim KH, Haynes MP, Bauer PM, Sanjay A, Collinge M, Baron R, Sessa WC, Bender JR, Variant estrogen receptor-c-Src molecular interdependence and c-Src structural requirements for endothelial NO synthase activation. Proc Natl Acad Sci U S A 104:42(16468-73)2007 Oct 16
17846174. Gil-Henn H, Destaing O, Sims NA, Aoki K, Alles N, Neff L, Sanjay A, Bruzzaniti A, De Camilli P, Baron R, Schlessinger J, Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2(-/-) mice. J Cell Biol 178:6(1053-64)2007 Sep 10
17094785. Sanjay A, Miyazaki T, Itzstein C, Purev E, Horne WC, Baron R, Identification and functional characterization of an Src homology domain 3 domain-binding site on Cbl. FEBS J 273:23(5442-56)2006 Dec
16313344. Horne WC, Sanjay A, Bruzzaniti A, Baron R, The role(s) of Src kinase and Cbl proteins in the regulation of osteoclast differentiation and function. Immunol Rev 208:(106-25)2005 Dec
15947003. Black VH, Sanjay A, van Leyen K, Lauring B, Kreibich G, Cholesterol and steroid synthesizing smooth endoplasmic reticulum of adrenocortical cells contains high levels of proteins associated with the translocation channel. Endocrinology 146:10(4234-49)2005 Oct
15872089. Bruzzaniti A, Neff L, Sanjay A, Horne WC, De Camilli P, Baron R, Dynamin forms a Src kinase-sensitive complex with Cbl and regulates podosomes and osteoclast activity. Mol Biol Cell 16:7(3301-13)2005 Jul
14739300. Miyazaki T, Sanjay A, Neff L, Tanaka S, Horne WC, Baron R, Src kinase activity is essential for osteoclast function. J Biol Chem 279:17(17660-6)2004 Apr 23
14528021. Chiusaroli R, Knobler H, Luxenburg C, Sanjay A, Granot-Attas S, Tiran Z, Miyazaki T, Harmelin A, Baron R, Elson A, Tyrosine phosphatase epsilon is a positive regulator of osteoclast function in vitro and in vivo. Mol Biol Cell 15:1(234-44)2004 Jan
14499658. Chiusaroli R, Sanjay A, Henriksen K, Engsig MT, Horne WC, Gu H, Baron R, Deletion of the gene encoding c-Cbl alters the ability of osteoclasts to migrate, delaying resorption and ossification of cartilage during the development of long bones. Dev Biol 261:2(537-47)2003 Sep 15
12530645. Black VH, Sanjay A, van Leyen K, Möeller I, Lauring B, Kreibich G, Cholesterol and steroid synthesizing smooth endoplasmic reticulum of adrenocortical cells contains high levels of translocation apparatus proteins. Endocr Res 28:4(425-30)2002 Nov
11724969. Sanjay A, Horne WC, Baron R, The Cbl family: ubiquitin ligases regulating signaling by tyrosine kinases. Sci STKE 2001:110(pe40)2001 Nov 27
11448952. Yokouchi M, Kondo T, Sanjay A, Houghton A, Yoshimura A, Komiya S, Zhang H, Baron R, Src-catalyzed phosphorylation of c-Cbl leads to the interdependent ubiquitination of both proteins. J Biol Chem 276:37(35185-93)2001 Sep 14
11149930. Sanjay A, Houghton A, Neff L, DiDomenico E, Bardelay C, Antoine E, Levy J, Gailit J, Bowtell D, Horne WC, Baron R, Cbl associates with Pyk2 and Src to regulate Src kinase activity, alpha(v)beta(3) integrin-mediated signaling, cell adhesion, and osteoclast motility. J Cell Biol 152:1(181-95)2001 Jan 8
10826490. Fu J, Pirozzi G, Sanjay A, Levy R, Chen Y, De Lemos-Chiarandini C, Sabatini D, Kreibich G, Localization of ribophorin II to the endoplasmic reticulum involves both its transmembrane and cytoplasmic domains. Eur J Cell Biol 79:4(219-28)2000 Apr
9748289. Sanjay A, Fu J, Kreibich G, DAD1 is required for the function and the structural integrity of the oligosaccharyltransferase complex. J Biol Chem 273:40(26094-9)1998 Oct 2
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Graduate Students Supervised:
Tracy Brennan, 2005 - present
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