Risbud Research

Madhu, V., Hernandaz-Meadows, M., Coleman, A., Sao, K., Inguito, K., Haslam, O., Boneski, P.K., Sesaki, H., Barve, R.A., Collins, J.A. & Risbud, M.V. The loss of OPA1 accelerates intervertebral disc degeneration and osteoarthritis in aged mice. Nat Commun 16, 5996 (2025).

Our findings underscore that maintenance of mitochondrial dynamics and multi-organelle cross-talk is critical in preserving metabolic homeostasis of disc and cartilage.

Novais, E.J., Ottone, O.K., Brown, E.V., Madhu, V., Tran, V.A., Ramteke, P., Dighe, A.S., Solga, M.D., Manchel, A., Lepore, A.C. & Risbud, M.V. Genetics- and age-driven neuroimmune and disc changes underscore herniation susceptibility and pain-associated behaviors in SM/J mice. Sci. Adv.11, eado6847 (2025).

This study highlights the contribution of genetic background and aging to increased susceptibility of spontaneous intervertebral disc herniations in a clinically relevant murine model.

Ramteke, P., Watson, B., Toci, M., Tran, V.A., Johnston, S., Tsingas, M., Barve, R.A., Mitra, R., Loeser, R.F., Collins, J.A. & Risbud, M.V. Sirt6 deficiency promotes senescence and age-associated intervertebral disc degeneration in mice. Bone Res 13, 50 (2025). 

Our study highlights the contribution of SIRT6 in modulating DNA damage, autophagy, and cell senescence and its importance in maintaining disc health during aging, thereby underscoring it as a potential therapeutic target to treat intervertebral disc degeneration.

Johnston, S.N., Silagi, E.S., Madhu, V., Nguyen, D.H., Shapiro, I.M. & Risbud, M.V. GLUT1 is redundant in hypoxic and glycolytic nucleus pulposus cells of the intervertebral disc. JCI insight vol. 8,8 e164883. (2023). 

These observations provide the first evidence to our knowledge of functional redundancy in GLUT transporters in the physiologically hypoxic intervertebral disc and underscore the importance of glucose as the indispensable substrate for NP cells.

Ohnishi, T., Tran, V., Sao, K., Ramteke, P., Querido, W., Barve, R.A., van de Wetering, K. & Risbud, M.V. Loss of function mutation in Ank causes aberrant mineralization and acquisition of osteoblast-like-phenotype by the cells of the intervertebral disc. Cell Death Dis 14, 447 (2023). 

The present study provides new insights into the role of ANK in the disc tissue compartments and highlights the importance of local inorganic pyrophosphate metabolism in inhibiting the mineralization of this important connective tissue.

Novais, E.J., Tran, V.A., Johnston, S.N., Darris, K.R., Roupas, A.J., Sessions, G.A., Shapiro, I.M., Diekman, B.O. & Risbud, M.V. Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice. Nat Commun 12, 5213 (2021). 

This study shows the importance of senescence as a key player in age-dependent intervertebral disc degeneration and highlights the use of senolytics to ameliorate it.