Investigator, Instructor (M) Nephrology, Mass General Research Institute

Instructor in Medicine Harvard Medical School

alphallbbeta3; alphavbeta3; beta2; cardiomyopathy dilated; cell stretching; electrocardiography ambulatory; focal adhesions; heart conduction system; integrin alphavbeta3; integrins; intracellular stress tomography; magnetic tweezers; mechanochemical signaling; podocytes; spontaneous bead motion; structure-function relationship of integrins; traction microscopy

Structure-activity relationships in integrins

Our lab is working on the structure-function relationship of the integrin receptors, in particular Beta2, AlphavBeta3, and AlphaIIbBeta3 integrins. They are expressed on the cell surface in an inactive state, thereby preventing cells from inappropriately adhering to each other or to the ECM unless activated by a physiologic stimulus (inside-out signaling).

Then, integrins undergo rapid and reversible conformational-dependent changes in affinity, and avidity. Binding of ligand and/or application of external mechanical forces causes further changes in integrin conformation, and this change transduces an outside-in signal to the cell interior. We are testing specific, structure-based hypothesis for integrin activation and signaling. We are also developing novel techniques for fluorescent analysis of integrins and to probe activation induced conformational changes in integrins on live cells.

Mechanochemical signaling in podocytes

The goal of this project is to study the molecular basis of cellular mechano-chemical signaling and cell mechanical behavior in renal podocytes. We address these questions using magnetic tweezers, cell stretching, traction microscopy, intracellular stress tomography, and spontaneous bead motion. This work is carried out in collaboration with the Biophysics Dept. of the University of Erlangen-Nuremberg.