Researchers have developed a method to design drugs that efficiently block rather than activate critical cell receptors which may help avoid adverse medication outcomes.
Explore This Research Lab
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.
- Goldmann WH, Alonso JL, et al. Cell Shape Control and Mechanical Signalling through the Cytoskeleton. In: Carraway KL, Carraway CAC, editors. Cytoskeleton: Signaling and Cell Regulation. A Practical Approach.Oxford, England: Oxford University Press; 2000. p. 245-76.
- Alonso JL, Essafi M, Xiong J-P, Stehle T, Arnaout MA. Does the integrin alphaA Domain Act as a Ligand for its betaA Domain? Curr. Biol. 2002; 12: R340-2.
- Alonso JL, Goldmann WH. Feeling the Forces: Atomic Force Microscopy in Cell Biology. Life Sciences. 2003; 72: 2553-60.
- Chen CS, Alonso JL, Ostuni E, Whitesides GM, Ingber DE. Cell Shape provides Global Control of Focal Adhesion Assembly. Biochem Biophys Res Commun. 2003; 307: 355-61.
- Gupta V, Gylling A, Alonso JL, Sugimori T, Ianakiev P, Xiong J-P, Arnaout MA. The beta-tail domain (betaTD) regulates physiologic ligand binding to integrin CD11b/CD18. Blood. 2007; 109: 3513-3520.
- Alonso JL*, Gupta V*, Sugimori T, Essafi M, Xiong J-P, Arnaout MA. Role of the beta-Subunit Arginine/Lysine finger in Integrin Heterodimer Formation and Function. J. Immunol. 2008; 108: 1713-1718.
- Klemm AH, Diez G, Alonso JL, Goldmann WH. Comparing the mechanical influence of vinculin, focal adhesion kinase and p53 in mouse embryonic fibroblasts. Biochem. Biophys. Res. Commun. 2009; 379: 799-801.
- Xiong J-P, Mahalingham B, Alonso JL, Borrelli LA, Rui X, Anand S, Hyman BT, Rysiok T, Muller-Pompalla D, Goodman SL, Arnaout MA. Crystal Structure of the complete alphaVbeta3 Ectodomain plus an a/b Transmembrane Fragment. J Cell Biol. 2009; 186: 589-600.
- Press Release
- Oct | 16 | 2019
Linemen's rapid weight gain can lead to hardening of heart, arteries, but problems may be offset with increased aerobic training
- Sep | 24 | 2019
Bone health specialists typically spend their time trying to figure how to slow or stop the bone loss that leads to osteoporosis. What if they could find a new way to stimulate the growth of new bone tissue instead?
- Press Release
- Jun | 25 | 2019
A biological pathway previously found to contribute to the impact of stress on the risk of cardiovascular disease also may underlie the increased incidence of such disease experienced by individuals with lower socioeconomic status.
- Press Release
- Jun | 13 | 2019
A study based at the Ragon Institute of MGH, MIT and Harvard has determined how a pregnant woman’s vaccine-induced immunity is transferred to her child, which has implications for the development of more effective maternal vaccines.
- Press Release
- Jun | 11 | 2019
A study from Massachusetts General Hospital researchers finds that electronic consultations in allergy and immunology can simplify the process of providing the most appropriate care, often reducing the need for in-person specialist visits.
About the Nephrology Division
The Division of Nephrology at Massachusetts General Hospital is a leading provider of services for patients with kidney disease, including diagnosis and management of kidney diseases and medical management of renal transplantation.