Makarand V. Risbud, PhD

James J. Maguire Jr. Professor of Spine Research, Orthopaedic Surgery
Division Director , Orthopaedic Research
Co-Director, Cell Biology & Regenerative Medicine Graduate Program

Makarand V. Risbud, PhD

Contact

1015 Walnut Street
Suite 501, Curtis Bldg.
Philadelphia, PA 19107

Email Makarand Risbud

215-955-1063

Makarand V. Risbud, PhD

James J. Maguire Jr. Professor of Spine Research, Orthopaedic Surgery
Division Director , Orthopaedic Research
Co-Director, Cell Biology & Regenerative Medicine Graduate Program

Expertise and Research Interests

Major research focus of my lab is to study the mechanisms by which nucleus pulposus cells of the intervertebral disc adapt to avascular (hypoxic) and osmotically compromising environment. In this regard, we are studying role of transciption factors HIFs and TonEBP and signaling events that control their function. Another major research interest is to device tissue-enginering based strategies for intervertebral disc regeneration. We are testing hypothesis that adult mesenchymal stem cells (MSC) transplanted into the disc will assume nucleus pulposus-like phenotype and achieve functional restoration of degenerate disc. Our recent work shows that MSC differentiate into nucleus pulposus-like cells when cultured under conditions similar to that exist in the disc in vivo. A whole disc organ culture is also under investigation to understand aspects of disc cell function in an ex vivo setting.

Education

PhD, National Center for Cell Science, India - 2001

MTech, Indian Institute of Technology (IIT): Bombay - 1999

MSc, Biochemistry, University of Pune - 1997

Fellowship: Post Doc Fellowship, Harvard University, Boston, 2001-2002

Publications

Other Expertise

 

Cell-Scaffold intereactions at molecular level and chitosan based scaffolds

Industrial Relevance

 

My reaserch has a strong translational component. Regeneration of degenerate intervertberal disc using adult-mesenchymal stem cells could be a clinical therapy in future and is of immense interest to many biotech and health science companies.

Keywords

 

Intervertebral Disc; Mesenchymal Stem Cells; Nucleus Pulposus Cells; Hypoxia; HIF-1, hypertonicity, TonEBP, Cell signaling; Tissue Engineering, Scaffolds

Languages

 

English, Hindi, Marathi

Most Recent Peer-Reviewed Publications

 

  1. RNA binding protein HuR regulates extracellular matrix gene expression and pH homeostasis independent of controlling HIF-1α signaling in nucleus pulposus cells
  2. A New Understanding of the Role of IL-1 in Age-Related Intervertebral Disc Degeneration in a Murine Model
  3. Transgenic mice overexpressing human TNF-α experience early onset spontaneous intervertebral disc herniation in the absence of overt degeneration
  4. p16 Ink4a deletion in cells of the intervertebral disc affects their matrix homeostasis and senescence associated secretory phenotype without altering onset of senescence
  5. NFAT5/TonEBP controls early acquisition of notochord phenotypic markers, collagen composition, and sonic hedgehog signaling during mouse intervertebral disc embryogenesis
  6. Expression of Carbonic Anhydrase III, a Nucleus Pulposus Phenotypic Marker, is Hypoxia-responsive and Confers Protection from Oxidative Stress-induced Cell Death
  7. Glycosaminoglycan synthesis in the nucleus pulposus: Dysregulation and the pathogenesis of disc degeneration
  8. A novel mouse model of intervertebral disc degeneration shows altered cell fate and matrix homeostasis
  9. Bicarbonate Recycling by HIF-1–Dependent Carbonic Anhydrase Isoforms 9 and 12 Is Critical in Maintaining Intracellular pH and Viability of Nucleus Pulposus Cells
  10. COX-2 expression mediated by calcium-TonEBP signaling axis under hyperosmotic conditions serves osmoprotective function in nucleus pulposus cells
  11. Lack of evidence for involvement of TonEBP and hyperosmotic stimulus in induction of autophagy in the nucleus pulposus
  12. PHD3 is a transcriptional coactivator of HIF-1a in nucleus pulposus cells independent of the PKM2-JMJD5 axis
  13. New horizons in spine research: Intervertebral disc repair and regeneration
  14. TNF-α promotes nuclear enrichment of the transcription factor TonEBP/NFAT5 to selectively control inflammatory but not osmoregulatory responses in nucleus pulposus cells
  15. RNA sequencing reveals a role of TonEBP transcription factor in regulation of pro-inflammatory genes in response to hyperosmolarity in healthy nucleus pulposus cells a homeostatic response?
  16. Hypoxia promotes noncanonical autophagy in nucleus pulposus cells independent of MTOR and HIF1A signaling
  17. New Horizons in Spine Research: Disc biology, spine biomechanics and pathomechanisms of back pain
  18. Molecular mechanisms of biological aging in intervertebral discs
  19. N-cadherin is key to expression of the nucleus pulposus cell phenotype under selective substrate culture conditions
  20. Class i and IIa HDACs Mediate HIF-1α Stability Through PHD2-Dependent Mechanism, while HDAC6, a Class IIb Member, Promotes HIF-1α Transcriptional Activity in Nucleus Pulposus Cells of the Intervertebral Disc