Research Summary

It is now well established that our material body operates based on a complex system of physical forces. Imbalances in these vital forces are increasingly recognized as the primary cause for the development and progression of major diseases such as cancers, diabetes, stroke, cardiovascular issues, neurological disorders, and abnormal aging. These conditions lead to a diminished quality of life and societal burden. The mechanical forces involved include solid forces, such as the stiffening of the extracellular matrix (ECM), and fluid forces, such as changes in hydrostatic pressure and shear stresses. Our recent research has demonstrated that in addition to the conventional solid and fluid forces, specific, often overlooked force-generating agents-such as the stress induced by high glucose levels (hyperosmotic stress) and fluid pressure changes brought about by macropinocytosis-play critical roles in disease therapeutics. Importantly, our work has advanced the understanding that the high concentration of protons in the microenvironment (low pH), along with secreted galectins and amyloids, are potential unconventional force-generating agents. They affect membrane phase separation and tensional homeostasis, thereby impacting disease progression and treatment.
Mechanotherapy, which involves modulating sensors and effectors in mechanical force adaptation, is emerging as a leading field in reconstructive medicine. Therefore, my laboratory's mission is to decipher how cells can combat non-physiological biomechanical alterations to re-establish healthy homeostasis. We aim to enhance our understanding on how cells sense and adapt to mechanical forces, especially under chronic biomechanical threats such as those occurring during cancers, brain injuries, degenerative diseases, left ventricular hypertrophy of the heart, diabetes, obesity and hypertension.
Conversely, we seek to uncover how tumor cells efficiently adapt to harsh biomechanical microenvironments and identify ways to disrupt this adaptation to promote tumor cell death. Additionally, understanding tumor cell mechanoadaptation strategies can provide insights into the molecular potential of cells to withstand harsh microenvironmental challenges. This knowledge can be leveraged to pharmacologically enhance the survival of degenerating cells, unlike tumor cells, which perish under similar conditions.
Therefore, a comprehensive multi-omics-based understanding of the interactions between biomechanical force-generating agents and mechanoadaptive machinery will facilitate the development of therapeutics that target key molecular players involved in disease pathogenesis, ultimately enabling recovery from diseased states. In this regard, my laboratory focuses on two broad themes: understanding the mechanobiology and mechano-therapeutics of cancers, and addressing cerebrovascular-cardiovascular life-threatening ailments & abnormal aging.
Our aims include:

1. Understanding the mechanobiology of tumor cells for targeted therapeutics.
2. Identifying the dominant biomechanical force-generating agents associated with pathophysiologies of the brain, heart, and kidneys.
3. Exploring the mechanobiology of the brain, heart, and immune systems to facilitate effective recovery and regeneration.