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Faculty Affairs: Faculty Interests Database Makarand V. Risbud, Ph.D.

Orthopaedic Surgery
Thomas Jefferson University
Jefferson Medical College
Department of Orthopaedic Surgery
Professor
Appointed: 2002

Graduate Program in Cell and Developmental Biology
and Track in Tissue Eng. and Regenerative Medicine
Thomas Jefferson University
Mailing Address Contact Information
1025 Walnut St., Suite 511, College Bldg.
Philadelphia, Pennsylvania 19107
United States
mAKARAND.RISBUD@jefferson.edu
Qualifications
M.Sc., Biochemistry, University of Pune, 1997
M.Tech., Indian Institute of Technology (IIT): Bombay, 1999
Ph.D., National Center for Cell Science, India, 2001
Post Doc Fellowship, Harvard University, Boston, 2001-2002
Expertise and Research Interests
Our work is focused on understanding how aberrant changes in the microenvironment compromise nucleus
pulposus cell function and promote development of degenerative disc disease, a leading cause of chronic
back/neck pain and disability. Nucleus pulposus cells reside in avascular and hyperosmolar niche of the disc,
we are studying contribution of transcription factors HIF-1 and TonEBP to their adaptation to these niche
conditions. Other focus of the lab to investigate how inflammatory cytokines TNF and IL-1 contribute to disc
degeneration.
Industrial Relevance
My reaserch has a strong translational component. Regeneration of degenerate intervertberal disc using cell
based therapies could be a clinical therapy in future and is of immense interest to many biotech and health
science companies.
Keywords
Intervertebral Disc; Nucleus Pulposus Cells; Hypoxia; HIF-1, hypertonicity, TonEBP, Cell signaling; Tissue Engineering, Mesenchymal Stem Cells; Scaffolds
Languages
English, Hindi, Marathi
Publications
  • Risbud MV, Sittinger M. Tissue Engineering: Advances in In Vitro Cartilage Generation. Trends in
  • Biotechnology 2002, 20: 351-356
  • Risbud MV. Izzo MW. Albert TJ. Shapiro IM. An organ culture system for the study of the nucleus pulposus:
  • Description of the system and evaluation of the cells. Spine 2003; 28: 2652-8.
  • Hutmacher DW. Sittinger M., Risbud MV, Scaffold-based tissue engineering: rationale for computer-aided
  • design and solid free-form fabrication systems. Trends Biotechnol. 2004; 22:354-362.
  • Sittinger M , Hutmacher DW, Risbud MV. Current strategies for cell delivery in cartilage and bone
  • regeneration. Curr. Opin Biotechnol 15:411-8, 2004
  • Risbud MV, Shapiro IM, Vaccaro AR, Albert TJ. Stem cell regeneration of the nucleus pulposus. Spine J.
  • 4:348S-353S,2004.
  • Risbud MV, Guttapalli A, Albert TJ. Vresilovic E, Shapiro IM. Differentiation of mesenchymal stem cells
  • towards a nucleus pulposus-like phenotype in vitro: implications for cell based transplantation therapy.
  • Spine 29:2627-32,2004
  • Risbud MV. Fertala J, Vresilovic E, Albert TJ, Shapiro IM. Nucleus pulposus cells upregulate PI3K/Akt and
  • MEK/ERK signaling pathways under hypoxic conditions and resist apoptosis induced by serum withdrawal.
  • Spine 30:882-9,2005
  • Risbud MV, Guttapalli A, Albert TJ, Shapiro IM. Hypoxia activates MAPK activity in rat nucleus pulposus
  • cells: regulation of integrin expression and cell survival. Spine 30:2503-9, 2005.
  • Risbud MV, Shapiro IM, Guttapalli A, et al. Osteogenic potential of adult human stem cells of the lumbar
  • vertebral body and the iliac crest. Spine 31:83-9, 2006.
  • Risbud MV, Guttapalli A, Stokes DG, Hawkins D, Danielson KG, Schaer TP, Albert TJ, Shapiro IM. Nucleus
  • pulposus cells express HIF-1a under normoxic culture conditions: A metabolic adaptation to the
  • intervertebral disc microenvironment. J Cell Biochem. 2006;98:152-9.
  • Tsai TT, Danielson KG, Guttapalli A, Oguz E, Albert TJ, Shapiro IM, Risbud MV. TonEBP/OREBP is a
  • regulator of nucleus pulposus cell function and survival in the intervertebral disc. J Biol Chem. 2006;
  • 281:25416-25424.
  • Tsai TT, Guttapalli A, Agrawal A, Albert TJ, Shapiro IM, Risbud MV. MEK/ERK Signaling Controls
  • Osmoregulation of Nucleus Pulposus Cells of the Intervertebral Disc by Transactivation of TonEBP/OREBP.
  • J Bone Miner Res. 2007; 22:965-974.
  • Agrawal A, Guttapalli A, Narayan SB, Albert TJ, Shapiro IM, Risbud MV. Normoxic stabilization of HIF-
  • 1alpha drives glycolytic metabolism and regulates aggrecan gene expression in rat nucleus pulposus cells
  • of the intervertebral disc. Am J Physiol Cell Physiol. 2007; 293(2):C621-31
  • Zeng Y, Danielson KG, Albert TJ, Shapiro IM, Risbud MV. HIF-1alpha is a Regulator of Galectin-3
  • Expression in the Intervertebral Disc. J Bone Miner Res. 2007; 22(12):1851-61.
  • Uchiyama Y, Cheng CC, Danielson KG, Mochida J, Albert TJ, Shapiro IM, Risbud MV. Expression of acid-
  • sensing ion channel 3 (ASIC3) in nucleus pulposus cells of the intervertebral disc is regulated by p75NTR
  • and ERK signaling. J Bone Miner Res. 2007;22):1996-2006.
  • Risbud MV, Guttapalli A, Tsai TT, Lee JY, Danielson KG, Vaccaro AR, Albert TJ, Gazit Z, Gazit D, Shapiro
  • IM. Evidence for skeletal progenitor cells in the degenerate human intervertebral disc. Spine.
  • 2007;32(23):2537-44.
  • Uchiyama Y, Guttapalli A, Gajghate S, Mochida J, Shapiro IM, Risbud MV. SMAD3 functions as a
  • transcriptional repressor of acid-sensing ion channel 3 (ASIC3) in nucleus pulposus cells of the intervertebral
  • disc. J Bone Miner Res. 2008;23(10):1619-28.
  • Agrawal A, Gajghate S, Smith H, Anderson DG, Albert TJ, Shapiro IM, Risbud MV. Cited2 modulates
  • hypoxia-inducible factor-dependent expression of vascular endothelial growth factor in nucleus pulposus
  • cells of the rat intervertebral disc. Arthritis Rheum. 2008;58(12):3798-808.
  • Gajghate S, Hiyama A, Shah M, Sakai D, Anderson DG, Shapiro IM, Risbud MV. Osmolarity and
  • Intracellular Calcium Regulate Aquaporin2 Expression Through TonEBP in Nucleus Pulposus Cells of the
  • Intervertebral Disc. J Bone Miner Res. 2009; 24:992-1001
  • Hiyama A, Gajghate S, Sakai D, Mochida J, Shapiro IM, Risbud MV. Activation of TonEBP by calcium
  • controls beta 1,3 glucuronosyl transferase-I (GlcAT-I) expression, a key regulator of glycosaminoglycan
  • synthesis in cells of the intervertebral disc. J Biol Chem. 2009 284:9824-34
  • Cheng CC, Uchiyama Y, Hiyama A, Gajghate Shapiro IM, Risbud MV. PI3K/AKT Regulates Aggrecan Gene
  • Expression by Modulating Sox9 Expression and Activity in Nucleus Pulposus Cells of the Intervertebral
  • Disc. J Cell Physiol. 2009; 221:668-76.
  • Hiyama A, Gogate SS, Gajghate S, Mochida J, Shapiro IM, Risbud MV. BMP-2 and TGFb Stimulate
  • Expression of beta1,3 Glucuronosyl Transferase-I (GlcAT-I) in Nucleus Pulposus Cells Through AP1,
  • TonEBP and Sp1: Role of Map Kinases. J Bone Miner Res. 2010;25:1179-90.
  • Saraiya M, Nasser R, Zeng Y, Addya S, Ponnappan RK, Fortina P, Anderson DG, Albert T, Shapiro IM,
  • Risbud MV. Reversine Enhances Generation of Progenitor-Like Cells By De-Differentiation Of Annulus
  • Fibrosus Cells.Tissue Eng Part A. 2010; 16:1443-55
  • Risbud MV, Schipani E, Shapiro IM. Hypoxic regulation of nucleus pulposus cell function: fom niche to
  • notch. Am J. Pathol 2010;176:1577-83
  • Tran CM, Markova D, Smith H, Susarla B, Ponnappan R, Anderson DG, Symes A, Shapiro IM, Risbud MV.
  • Regulation of CCN2/CTGF Expression in the Nucleus Pulposus of the Intervertebral Disc: Role of Smad and
  • AP1 Signaling" Arthritis Rheum. 2010, 62:1983-92.
  • Skubutyte R, Markova D, Freeman T, Anderson DG, Dion S, Williams CJ, Shapiro IM, Risbud MV. HIF
  • Regulation of ANK Expression in Nucleus Pulposus Cells: Possible Implications in Controlling Dystrophic
  • Mineralization in the Intervertebral Disc Arthritis Rheum 2010, 62:2707-15
  • Shapiro IM, Risbud MV. Transcriptional profiling of the nucleus pulposus: say yes to notochord. Arthritis
  • Res Ther. 2010; 12:117.
  • Hiyama A, Mochida J, Risbud MV, Sakai D. Enhanced intervertebral disc cells senescence by Wnt/b-
  • catenin signaling-induced matrix metalloproteinase expression. Arthritis Rheum. 2010 62:3036-47
  • Risbud MV, Schaer T, Shapiro IM. Towards an understanding of the role of notochordal cells in the
  • intervertebral disc: from discord to accord Dev Dyn 2010, 239:2141-8
  • Hiyama A, Skubutyte R, Markova D, Anderson DG, Yadla S, Sakai D, Mochida J, Albert TJ, Shapiro IM,
  • Risbud MV. Hypoxia Activates Notch Signaling Pathway in the Cells of the Intervertebral Disc: Implications
  • in Degenerative Disc Disease. Arthritis Rheum. 2011, 63:1355-64.
  • Gogate S, Nasser R, Shapiro IM, Risbud MV. Hypoxic Regulation of beta 1,3 Glucuronosyl Transferase-I
  • (GlcAT-I) Expression in Nucleus Pulposus Cells of The Intervertebral Disc: Role of HIF Proteins. Arthritis
  • Rheum. 2011, 63:1950-60.
  • Risbud MV, Shapiro IM. Notochordal cells in the adult intervertebral disc: new perspective on an old
  • question. Crit Rev Eukaryot Gene Expr. 2011, 21:29-41.
  • Wang J, Markova D, Anderson DG, Zheng Z, Shapiro IM, Risbud MV. TNF-a and IL-1b promote a disintegrin-
  • like and metalloprotease with thrombospondin type I motifs (ADAMTS) -5 mediated aggrecan degradation
  • through syndecan-4 in intervertebral disc. J Biol Chem. 2011;286:39738-49.
  • Tran CM, Smith H, Symes A, Rittie L, Perbal B, Shapiro IM, Risbud MV. TGF-b Controls CCN3 Expression
  • in Nucleus Pulposus Cells of the Intervertebral Disc. Arthritis Rheum. 2011;63:3022-31.
  • Ponnapan R, Markova D, D Antonio PJ, Murray HB, Vaccaro AR, Shapiro IM, Anderson DG, Albert TJ,
  • Risbud MV. An organ culture system to model early degenerative changes of the intervertebral disc. Arthritis
  • Res Ther 2011;13:R171
  • Fujita N, Chiba K, Shapiro IM, Risbud MV. HIF-1a and HIF-2a degradation is differentially regulated in
  • nucleus pulposus cells of the intervertebral disc. J Bone Miner Res. 2012; 27:401-12.
  • Fujita N, Markova D, Anderson DG, Chiba K, Toyama Y, Shapiro IM, Risbud MV. Expression of prolyl
  • hydroxylases (PHDs) is selectively controlled by HIF-1 and HIF-2 proteins in nucleus pulposus cells of the
  • intervertebral disc: distinct roles of PHD2 and PHD3 proteins in controlling HIF-1 activity in hypoxia. J Biol
  • Chem. 2012; 287:16975-86.
  • Fujita N, Gogate SS, Chiba K, Toyama Y, Shapiro IM, Risbud MV. Prolyl hydroxylase 3 (PHD3) modulates
  • catabolic effects of TNF-± on cells of the nucleus pulposus through co-activation of NF-ºB/p65 signaling. J
  • Biol Chem. 2012; 287:39942-53
  • Wu Q, Wang J, Skubutyte R, Kepler CK, Huang Z, Anderson DG, Shapiro IM, Risbud MV. SMAD3 controls
  • b1, 3 glucuronosyl transferase I (GlcAT-I) expression in nucleus pulposus cells: Implications of disregulated
  • expression in disc disease. Arthritis Rheum. 2012; 64:3324-33
  • Gogate SS, Fujita N, Skubutyte R, Shapiro IM, Risbud MV. TonEBP and HIF coordinate Hsp70 expression
  • in hypoxic nucleus pulposus cells: Role of Hsp70 in HIF-1a degradation. J Bone Miner Res. 2012, 27:1106-
  • 17.
  • Shapiro IM, Vresilovic EJ, Risbud MV. Is the spinal motion segment a diarthrodial polyaxial joint: What a
  • nice nucleus like you doing in a joint like this? Bone. 2012;50:771-6.
  • Risbud MV, Shapiro IM. Gasping for air in the intervertebral disc: Hypoxia and HIF are critical for nucleus
  • pulposus cell survival and function. Arthritis Rheum. 2012;64:941-2.
  • Sakai D, Nakamura Y, Nakai T, Mishima T, Kato S, Grad S, Alini M, Risbud MV, Chan D, Cheah KSE,
  • Yamamura K, Masuda K, Okano H, Ando K, Mochida J. Exhaustion of nucleus pulposus progenitor cells
  • with ageing and degeneration of the intervertebral disc. Nature Communications 2012;3:1264. doi:
  • 10.1038/ncomms2226.
  • Markova DZ, Kepler CK, Addya S, Murray HB, Vaccaro AR, Shapiro IM, Anderson DG, Albert TJ, Risbud
  • MV. An organ culture system to model early degenerative changes of the intervertebral disc II: profiling
  • global gene expression changes. Arthritis Res Ther. 2013;15(5):R121.
  • Tran CM, Shapiro IM, Risbud MV. Molecular regulation of CCN2 in the intervertebral disc: lessons learned
  • from other connective tissues. Matrix Biol. 2013;32:298-306.
  • Tran CM, Fujita N, Huang BL, Ong JR, Lyons KM, Shapiro IM, Risbud MV. Hypoxia-inducible factor (HIF)-1a
  • and CCN2 form a regulatory circuit in hypoxic nucleus pulposus cells: CCN2 suppresses HIF-1a level and
  • transcriptional activity. J Biol Chem. 2013; 288:12654-66.
  • Wang H, Tian Y, Wang J, Phillips KL, Binch AL, Dunn S, Cross A, Chiverton N, Zheng Z, Shapiro IM, Le
  • Maitre CL, Risbud MV. Inflammatory Cytokines Induce NOTCH Signaling in Nucleus Pulposus Cells:
  • Implications in Intervertebral Disc Degeneration. J Biol Chem. 2013; 288:16761-74.
  • Tian Y, Yuan W, Fujita N, Wang J, Wang H, Shapiro IM, Risbud MV. Inflammatory cytokines associated
  • with degenerative disc disease control aggrecanase-1(ADAMTS-4) expression in nucleus pulposus cells
  • through MAPK and NF-ºB. Am J Pathol. 2013; 182:2310-21.
  • Wang J, Tian Y, Phillips K, Chiverton N, Haddock G, Bunning RA, Cross AK, Shapiro IM, LeMaitre CL,
  • Risbud MV. TNF-a and IL-1b dependent induction of CCL3 expression by nucleus pulposus cells promotes
  • macrophage migration through CCR1. Arthritis Rheum. 2013; 65:832-42. 14.
  • Risbud MV, Shapiro IM. Role of cytokines in intervertebral disc degeneration: pain and disc content. Nat Rev
  • Rheumatol. 2014 ;10:44-56.
  • Tran CM, Schoepflin ZR, Markova DZ, Kepler CK, Anderson DG, Shapiro IM, Risbud MV. CCN2 Suppresses
  • Catabolic Effects of Interleukin-1b through a5b1 and aVb3 Integrins in Nucleus Pulposus Cells:
  • IMPLICATIONS IN INTERVERTEBRAL DISC DEGENERATION. J Biol Chem. 2014; 289:7374-87.
  • Fujita N, Hirose Y, Tran CM, Chiba K, Miyamoto T, Toyama Y, Shapiro IM, Risbud MV. HIF-1-PHD2 axis
  • controls expression of syndecan 4 in nucleus pulposus cells. FASEB J. 2014; 28:2455-2465.
  • Hirose Y, Johnson ZI, Schoepflin ZR, Markova DZ, Chiba K, Toyama Y, Shapiro IM, Risbud MV. FIH-1-Mint3
  • Axis Does Not Control HIF-1a Transcriptional Activity in Nucleus Pulposus Cells. J Biol Chem. 2014 May
  • 27. pii: jbc.M114.565101. [Epub ahead of print]
  • Wang X, Wang H, Yang H, Li J, Cai Q, Shapiro IM, Risbud MV. TNF-a and IL-1b dependent MMP-3
  • expression in nucleus pulposus cells requires cooperative signaling via Syndecan4 and MAPK-NF-kB axis:
  • Implications in inflammatory disc disease. Am. J. Pathol. 2014 (accepted. June 4)

Last Updated by Makarand Risbud, Ph.D.: Friday, September 2, 2011 12:36:10 PM

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