What are we looking for?
Our lab is interested in understanding the basic molecular rules by which a cell defines and maintains its identity and function.
Our main focus is on understanding the molecular basis of programming and reprogramming of cell-fate decisions during embryogenesis, homeostasis and aging. Additionally, we focus on devising molecular strategies to ‘hack’ these genetic networks that programs cell-fates to induce regenerative responses upon injury.
- Long non-coding RNA mediated regulation of cell-fate decisions during development and homeostasis:
The human body is composed of about hundreds of different cell types. The identity and function of these distinct cell types are precisely programmed by the regulatory networks encoded in the 3 billion base pairs of DNA that constitute the human genome. While 60% of our genome is transcribed, less than 2% of it is translated to proteins. In contrast to previous assumptions, this suggests that a significant majority of the regulatory information from the genome functions as RNAs, termed non-coding RNAs. Emerging evidences suggest that a substantial portion of these non-coding transcripts control myriad biological processes ranging from development to disease, establishing the vital role played by these RNA regulatory elements.
- Conserved metabolic mediators of tissue-specific aging:
A temporal decline in the functional and molecular integrity of an organism defines its ageing process. While multiple hallmarks of ageing have recently been enumerated, our understanding of their functional, molecular and temporal hierarchy remains incomplete. The significance of these hallmarks in the ageing process vary in a tissue/ cell type specific manner. Considering the physiological differences between organs, it is conceivable that their susceptibility to these distinct triggers of ageing can differ. Therefore, it is important to delineate those mechanisms that influence the ageing process of specific organs to better understand organismal ageing. We investigate evolutionarily conserved mechanisms that leads to aging of the heart.
(EMBO Reports 2019)
- RNA-regulons mediating cell-fate decisions during cardiac regeneration:
Heart failure is a leading cause of mortality and morbidity in the developed world, partly because of the minimal regenerative ability of the mammalian heart. However, several fish and amphibians do possess dramatic ability to regenerate damaged organs, including heart. We use a combinatorial approach including regeneration competent models, state-of-the art stem cell-based models and systems biology approaches to understand the hidden regulatory layers enabling organ/ tissue regeneration.
- Translational control over cell-fate decisions and homeostasis:
Precision in gene expression is essential to establish and maintain a cellular identity in embryonic development. Therefore, key regulatory mechanisms are in place at every step of developmental cell-fate transitions, ranging from transcriptional control to proteostasis. Interestingly, recent studies suggest that up to 60% of gene expression is regulated at the level of translation. Highlighting its importance in developmental gene regulation, slight alterations in mechanisms regulating translation leads to severe developmental defects or embryonic lethality. However, the role of translational regulation in shaping developmental gene expression landscape is poorly understood. Additionally, transient alterations in the translation of specific mRNAs can have profound changes in molecular homeostasis. Using human pluripotent stem cell based models we investigate currently unknown mediators that regulate translation to program cell-fate.