At the MSML, our area of research is in cell and tissue mechanobiology – The understanding of how organ/cell structure, function and biology are modulated by mechanical forces, in health and disease. This is a line of inquiry that seeks to understand the role of an organ’s environment, and not just innate genetics, in the initiation and progression of disease, and using this knowledge to develop novel therapeutic strategies. The study of cell function and disease in the context of mechanobiology is especially significant in organs and tissues that are in continuous dynamic motion during their function (e.g. the heart, heart valves, blood vessels and bone). Within this theme, my students and I have focused on two specific areas within the broad cardiovascular system:

Heart valve disease. Heart valve disease, specifically that of the aortic valve, affects approximately 3-5% of the American population and does not have any known cure; surgical intervention is the current standard of care. Research in my laboratory focuses on the role of altered mechanics in modifying cellular behavior, differentiation, and structural remodeling, leading to eventual degenerative valve disease. Insights from this research will provide insights into the early events that potentiate valve disease and identify specific genes and proteins that can be targeted for therapy, or used as bio-markers for early identification of disease progression.  Current funding: NSF CAREER; American Heart Association

Blood-brain barrier dysfunction following traumatic brain injury (TBI). TBI is a devastating injury characterized by damage to the brain and its vasculature due to an external mechanical force, with an estimated 10 million instances worldwide. TBI is also considered the “signature injury” in modern warfare. In most cases, a TBI is caused by a single impact. However, there are increasing instances of repetitive traumatic insults to the brain, that cause increased vulnerability to downstream pathology. While the majority of TBI-related research has focused on the neuronal structures of the brain, I am exploring how repeated TBI induces disruption of the microvasculature of the blood-brain barrier and its surrounding structures, leading to dysfunction of its barrier function and eventual neurodegenerative disease. Current funding: NSF; Department of Defense