CAREER: Mechanobiology of the Chromatin Remodeling: Implications in Gene Expression, Physiology, and Pathology

This Faculty Early Career Development (CAREER) grant supports research focused on discovering a fundamental mechanism inside the cell nucleus that may dramatically improve our understanding of how several degenerative diseases associated with fibrosis occur and progress. Many pathological conditions inside the human body are associated with an abnormal mechanical environment in the tissues. Optimal mechanical force is required inside tissues to keep the cells functional and healthy. This project will elucidate how the biological system's healthy or pathological mechanical environment affects the structure and function of cells and tissues through chromatin remodeling – a novel epigenetic determinant of gene expression inside the cell nucleus. This knowledge can potentially provide new therapeutic strategies to treat a myriad of degenerative diseases, such as fibrosis in the lungs, heart, kidney, liver, skin, and blood vessels. The proposed research will be complemented by establishing a comprehensive educational and outreach program based on curriculum enrichment, quantitative biology training, and disseminating biomechanics knowledge in K-12 and students underrepresented in STEM. This project aims to discover how the tensile force at the tissue level reaches the intranuclear space to remodel the chromatin and determine the gene expression. The researchers will utilize high-resolution single cell microscopy, knowledge of mechanics, and advanced image analysis techniques to answer several outstanding questions in mechanobiology. The work will address: 1) how mechanical forces drive chromatin remodeling and gene expression; 2) how the changes in chromatin remodeling and gene expression affect the cell and tissue mechanical properties that determine the tissue phenotype; and 3) how to intervene in the mechano-epigenetic pathway to restore normalcy in degenerated cells or tissues. This project will allow the PI to advance the boundaries of the existing knowledge in chromatin mechanobiology, epigenetics, and gene expression mechanisms and establish a long-term career in mechanobiology to solve various problems in life sciences and medicine. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.