The broad goal of our lab is to understand how cells and intracellular components coordinate with environmental cues during development, tissue homeostasis, regeneration, and pathological conditions. We have a specific focus on the dynamics of cell nucleus, its chromatin architecture and epigenetic mechanisms. We use several techniques such as in vitro model with cells in 2D or 3D platform, in vivo mouse model, microscopic imaging, image analysis and molecular biological assays to answer our scientific questions. Currently, we are are executing the following projects.
Mechanobiology of the chromatin remodeling
Cells respond to mechanical forces to trigger mechanotransduction pathways, and this has been known for almost three decades. Multiple mechanisms have been described to understand the underlying process, and they involve structures/ molecules at the cell membrane, in the cytoplasm and at the cell nuclear envelope. To move this field further, we are focusing on the specific proteins of the ‘chromatin remodeling complex’, a potential epigenetic modifier, that respond to the extracellular mechanical forces via sensing the intranuclear deformation. Using quantitative imaging analysis on live deforming cells and fixed cells, we are elucidating the complex mechanotransduction mechanism that involve the chromatin remodeling complex and other nuclear/ cytoplasmic proteins. This research might lead us to the understanding the biology of stem cells and the biology of degenerative diseases/ aging at the subcellular level. Such understanding will lead us to rational tissue engineering/ regenerative medicine paradigm where the stem cells require precise control of mechanical force, to understand the etiology of abnormal mechanical environment driven diseases, to understand how mechanics drives tissue development by determining single cell fate, and to understand how mechanics maintains tissue homeostasis and stem cell niche. To achieve the goals of the research program, we are also interested in creating novel biomaterial platforms that can enable us to answer challenging questions.
Discovery of the innate cellular regenerative response to stress
It is known that many tissues have some degree of regenerative ability. The cells in those tissues respond to the environmental stresses (mechanical, oxidative, osmotic, pH etc) and trigger the necessary regeneration pathway. However, this ability might degrade with aging in a tissue specific manner. Mesenchymal Stromal Cells and Muscle Stem Cells are thought to play a critical role in such regeneration process, specifically in the musculoskeletal tissues. However, it is not understood what specific mechanism they exploit for responding to stress, adapt to stress, and for triggering the regeneration pathways. It is also not clear whether and how such regenerative mechanisms are ‘memorized’ by cells for future degenerative conditions. Further, it is also not clear how those stress driven regeneration signals are communicated by those stem cells/ stromal cells to the resident primary cells in the corresponding tissue. Using in vitro cell culture and in vivo murine studies we are trying to discover the underlying mechanism that potentially happens at the chromatin level, in coordination with cytoplasm. If successful, this research will lead us to exploit the human body’s natural regeneration mechanism to efficiently treat degenerative diseases.