Mechanogenomics - Prof. G. V. Shivashankar

Cellular ageing is inevitable, but the underlying mechanisms are still unclear. Importantly, a major unmet challenge is to rejuvenate ageing cells for applications in regenerative medicine. To address this challenge, our group focusses on understanding the mechano-genomic mechanisms underlying cellular ageing and how ageing cells can be partially reprogrammed and rejuvenated using non-genetic methods for robust therapeutic interventions. Over the years, our group has demonstrated that mechanical confinement of cells results in modular changes in nuclear mechanotransduction, 3D chromosome organization and gene expression. Based on these studies, we recently discovered that growth of fibroblast cells under sustained mechanical confinement results in their partial reprogramming. In addition, we showed that re-differentiation of such partially reprogrammed aged fibroblasts, under appropriate matrix stiffness, results in their remarkable rejuvenation to younger-like fibroblast cell states, providing novel avenues for tissue regeneration and repair. In these studies, we employ multi-scale correlative bio-imaging methods combined with bioengineered interfaces, functional genomics, theoretical modeling, and machine learning.

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