Research

At the MSML (a.k.a Balalab), our area of research is in the development of organ-chip technologies to study 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 the following areas of research:

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 the laboratory focuses on the role of altered mechanics in modifying cellular behavior, differentiation, and structural remodeling, leading to eventual degenerative valve disease. We also collaborate with the Quinn laboratory to understand the evolution of label-free two-photon excited fluorescence metrics during valve disease progression. 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, We are 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. We collaborate with our commercial partners Nanomatronix LLC to advance our BBB-chip technology in this area of research. Current funding: NSF; Department of Defense 

Heart-chip for studying metabolic diseases. This project seeks to develop a novel heart-chip platform that mimics the beating of the heart and its associated chemical and electrical signaling in a portable, miniaturized, benchtop format. This heart-chip will be engineered using patient-derived cells; from both healthy donors and those that have mitochondrial diseases. This work is conducted in collaboration with the Iyer laboratory. Current funding: Department of Defense