Makarand V. Risbud, PhD
James J. Maguire Jr. Professor of Spine Research, Orthopaedic Surgery
Division Director , Orthopaedic Research
Contact Information
1015 Walnut Street
Suite 501, Curtis Bldg.
Philadelphia, PA 19107
James J. Maguire Jr. Professor of Spine Research, Orthopaedic Surgery
Division Director , Orthopaedic Research
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
- A new perspective on intervertebral disc calcification—from bench to bedside
- Sdc4 deletion perturbs intervertebral disc matrix homeostasis and promotes early osteopenia in the aging mouse spine
- Toward understanding the cellular control of vertebrate mineralization: The potential role of mitochondria
- Proteoglycan Dysfunction: A Common Link Between Intervertebral Disc Degeneration and Skeletal Dysplasia
- Increased HIF-2α activity in the nucleus pulposus causes intervertebral disc degeneration in the aging mouse spine
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
- RNA binding protein HuR regulates extracellular matrix gene expression and pH homeostasis independent of controlling HIF-1α signaling in nucleus pulposus cells
- A New Understanding of the Role of IL-1 in Age-Related Intervertebral Disc Degeneration in a Murine Model
- Transgenic mice overexpressing human TNF-α experience early onset spontaneous intervertebral disc herniation in the absence of overt degeneration
- p16 Ink4a deletion in cells of the intervertebral disc affects their matrix homeostasis and senescence associated secretory phenotype without altering onset of senescence
- NFAT5/TonEBP controls early acquisition of notochord phenotypic markers, collagen composition, and sonic hedgehog signaling during mouse intervertebral disc embryogenesis
- Expression of Carbonic Anhydrase III, a Nucleus Pulposus Phenotypic Marker, is Hypoxia-responsive and Confers Protection from Oxidative Stress-induced Cell Death
- Glycosaminoglycan synthesis in the nucleus pulposus: Dysregulation and the pathogenesis of disc degeneration
- A novel mouse model of intervertebral disc degeneration shows altered cell fate and matrix homeostasis
- Bicarbonate Recycling by HIF-1–Dependent Carbonic Anhydrase Isoforms 9 and 12 Is Critical in Maintaining Intracellular pH and Viability of Nucleus Pulposus Cells
- COX-2 expression mediated by calcium-TonEBP signaling axis under hyperosmotic conditions serves osmoprotective function in nucleus pulposus cells
- Lack of evidence for involvement of TonEBP and hyperosmotic stimulus in induction of autophagy in the nucleus pulposus
- PHD3 is a transcriptional coactivator of HIF-1a in nucleus pulposus cells independent of the PKM2-JMJD5 axis
- New horizons in spine research: Intervertebral disc repair and regeneration
- TNF-α promotes nuclear enrichment of the transcription factor TonEBP/NFAT5 to selectively control inflammatory but not osmoregulatory responses in nucleus pulposus cells
- 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?
- Hypoxia promotes noncanonical autophagy in nucleus pulposus cells independent of MTOR and HIF1A signaling
- New Horizons in Spine Research: Disc biology, spine biomechanics and pathomechanisms of back pain
- Molecular mechanisms of biological aging in intervertebral discs
- N-cadherin is key to expression of the nucleus pulposus cell phenotype under selective substrate culture conditions
- 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