- Multi-scaled experimental frameworks for vascular biomechanics and growth & remodeling in health and disease. Mechanically-mediated vascular remodeling occurs as cells sense and respond to changes in their local mechanical environment; these mechanisms play key roles in many physiological and pathophysiological processes, as well as in the outcomes of many clinical interventions; examples include arterial stiffening with age, the development and progression of aneurysms and atherosclerosis, and restenosis of vascular grafts. Our group has also developed an experimental framework to perform biaxial mechanical testing on small caliber vessels (100 – 2,000 microns) and multi-photon microscopy on the same live tissue, under controlled mechanical loading. This experimental framework also allows for organ culture for periods of days to weeks. These data provide multi-scale experimental data, which are necessary for developing and testing multi-scale mathematical models of tissue biomechanics and remodeling (Contribution 2).
- Multi-scaled computational frameworks for vascular biomechanics and growth & remodeling in health and disease. My research in this area has led to the development of novel mathematical modeling approaches that capture changes in the content and organization of cells and extracellular matrix to predict changes in the biomechanical response of these tissue in health and disease. We have applied and integrated these computational frameworks with our experimental approaches to quantify the changes in cell and ECM content and organization in normal development and in the progression of vascular disease.
- Characterizing mechanically mediated acute and long-term adaptations of lymphatic vessels in the development and progression of lymphedema. The lymphatic vasculature plays a key role in immune cell trafficking, transport of lymph fluid from peripheral tissues to the central venous system, and in transport of lipids from the gut to the circulation during absorption, from adipose and other peripheral tissues to the liver, and in reverse cholesterol transport of lipids from atherosclerotic plaques. Primary and secondary lymphedema are characterized by the loss of pumping function of lymphatic vessels of the affected limbs, resulting in localized fluid retention and swelling. Secondary lymphedema is a common complication following breast cancer treatment and we submit that the underlying mechanisms of lymphedema development and progression are mechanically mediated. The relationship between the local mechanical environment, mechano-biological mechanisms, long-term lymphatic function, and progression of lymphedema is largely unknown. Our group is developing computational frameworks to quantify mechanically mediated adaptations of lymphatic vessels and performing theoretically motivated experiments to parse the underlying mechanisms of lymphedema.