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Our laboratory, established in fall 2003, focuses on the interplay between mechanical forces, cell biology, and integrated organ physiology. The central issues are: (1) how a cell actively develops mechanical forces, and how these forces affect chemical transitions (for example in the actomyosin ATPase cycle); (2) how a cell senses and responds to mechanical forces; and (3) how changes in protein-protein interactions of the cytoskeletal elements and accessory proteins inside the cell can affect cell or organ properties and their function. We bring to this research area an interdisciplinary approach that spans engineering science, computational science, biology, biochemistry, and biophysics. We combine molecular, cellular, and whole organ approaches in order to understand cell and tissue biology, muscle physiology, and whole organ physiology.

A major effort over the last 10 years has been the development of the computational platform: MUSICO (Muscle Simulation Code). The interdisciplinary approach implemented in MUSICO allows researchers to unveil the molecular origins of physiological functions or dysfunctions of all muscle types: skeletal, cardiac, smooth and insect flight muscle. The platform integrates experimental data at multiple scales including cross-bridge kinetics and regulation, structure of contractile proteins, interaction between the contractile proteins and their assembly in sarcomeres in striated muscle and sarcometric structures in smooth muscle. Experimentally determined parameters implemented in MUSICO are partially derived from data collected in our lab and partially via an international multi-institutional effort with several world-leading Universities. At larger length scales, the precise architecture of muscle at the organ level provided from diffusion tensor imaging (DTI) in concert with the MUSICO prediction of instantaneous active and passive characteristics of muscle provides a precise tool to trace the effects of molecular defects leading to impaired function of organs in disease. Currently developed applications of the MUSICO platform are studies of asthma and pulmonary hypertension, cardiomyopathies, muscle weakness and disorders of tongue function during swallowing.

My current research focuses on the development of quantitative approaches to study biological systems at multiple levels of organization (i.e. multiscale modeling). In particular I am interested in developing a theoretical framework that will advance our understanding of how cellular and subcellular phenomena integrate to impact structure-function and dynamic relations of whole physiological systems, based on the kinetics of underlying molecular processes.

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