Adjunct ProfessorDepartment of Medicine JHMI
Adjunct ProfessorDepartment of Materials Science Whiting School of Engineering.
Adjunct ProfessorDepartment of Pathology JHMI
Training Program in Immunology Program Project in T cell Immunology
Department of Biology
Johns Hopkins University
3400 N. Charles Street
Baltimore, MD 21218-2685
Office 410 516-7294
Lab 410 516-7295
Departmental fax 410 516-5213
B.S.University of Chicago
Ph.D.University College London
PostdoctoralThe Weizmann Institute
Harvard Medical School
|Note:||There are no research positions open in my unit, at any level, undergraduate to postdoctoral.|
Cell membranes are complex two-dimensional arrays of mobile, interacting molecules. My laboratory uses cell biology, biophysics, especially fluorescence methods, biochemistry and immunology to study membrane dynamics and organization in cells ranging from lymphocytes to epithelial cells.
All of our work on membranes arises from interests in transplantation immunology, especially in the cell biology of class I MHC molecules. We aim to understand the relationship between plasma membrane biophysics and antigen presentation by MHC molecules.
Our methods of analysis emphasize quantitative microscopy and image analysis, especially fluorescence recovery after photobleaching, FRAP, to measure lateral diffusion, and fluorescence resonance energy transfer, FRET, to measure molecular proximity and clustering. Work with these techniques as well as with other advanced microscopies, including deconvolution microscopy and total internal reflection microscopy, is done in a strong Departmental imaging facility with ample hardware and technical support.
We use our techniques to investigate the ways in which antigen presentation to, and antigen recognition by, T cells is affected changes in organization of membrane proteins at the cell surface. Cholesterol depletion of plasma membranes has large effects on antigen presentation by class I MHC molecules; these effects can be mimicked by drugs that affect the membrane skeleton and by class I MHC molecules that have been engineered so that they can be crosslinked and clustered by small membrane-permeable compounds. We have shown that increasing the size of class I MHC clusters enhances presentation of low concentrations of antigens.
In a collaboration with medical school colleagues we are currently investigating the clustering of T cell receptors for antigen, TCR. We have developed methods of specifically labeling TCR with quantum dots and using the unique photophysics of the quantum dot labels to report on changes in TCR clustering with time after activation of naïve T cells by antigen. We first used this approach for CD8+ T cell responses to class I MHC molecules.Currently we use quantum dot photophysics to characterize the clustering of class II MHC molecules on dendritic cells. The relationship between molecular clustering and immune response appears to be quite different for dendritic cells than for T cells.
Boyle, S., Kolin, D.L., Bieler, J.G., Schneck, J.P., Wiseman, P.W. and Edidin, M. Quantum dot fluorescence characterizes the nanoscale organization of T cell receptors for antigen. Biophys. J. 101: L57-L59 (2011)
Edidin, M. Class I MHC molecules as probes of membrane patchiness: from biophysical measurements to modulation of immune responses. Immunol Res. 2010 47:265-72 (2010)
Fooksman, D.R., Shaikh, S.R., Boyle, S. & Edidin, M. Phosphatidylinositol 4,5-bisphosphate concentration at the APC side of the immunological synapse is required for effector T cell function. J. Immunol 182: 5179-5182 (2009).
Abe F., Van Prooyen N., Ladasky J.J. & Edidin M. Interaction of Bap31 and class I MHC molecules and their traffic out of the endoplasmic reticulum. J. Immunol. 182: 4776-4783 (2009).
Shaikh, SR, Boyle, S., Hua, J., Li, Z. and Edidin M. In Vivo Test of the Vertical Phase Separation Hypothesis: The Display of MHC Class I Molecules on Membranes of B cells from Mice Fed High Fat Diets. British journal of Nutrition 101: 804-809 (2009).
Shaikh SR, Mitchell D, Carroll E, Li M, Schneck J and Edidin M. Differential effects of a saturated and a monounsaturated fatty acid on MHC class I antigen presentation. Scand J Immunol. 2008. 68:30-42.
Everett, M.W. and Edidin, M. 2007. Tapasin Increases Efficiency of MHC I Assembly in the Endoplasmic Reticulum but Does Not Affect MHC I Stability at the Cell Surface. The Journal of Immunology. 179:7646-52.
Fooksman, D.R., Edidin, M., and Barisas, B.G. 2007. Measuring rotational diffusion of MHC class I on live cells by polarized FPR. Biophys Chem. 130:10-6.
Shaikh SR, Edidin MA. 2006. Membranes are not just rafts. Chem Phys Lipids.144(1):1-3.
Ladasky, J.J., Boyle, S., Seth, M., Li, H., Pentcheva, T., Abe, F., Steinberg, S.J., Edidin, M. (2006). Bap31 enhances the ER export and quality control of human class I MHC molecules. J. Immuol. 177:6172-81..
Fooksman DR, Gronvall GK, Tang Q, Edidin M. (2006) Clustering class I MHC modulates sensitivity of T cell recognition. J Immunol. 176(11):6673-80.
Capps, G.G, Pine, S., Edidin, M., and Zúñiga, M.C. 2004 Short Class I MHC Cytoplasmic Tails Differing in Charge Detect Arbiters of Lateral Diffusion in the Plasma Membrane Biophys. J. 86, 896-909.
Kwik, J., Boyle, S., Fooksman, D. Margolis,L., Sheets, M.P. and Edidin, M. 2003. Membrane cholesterol, Lateral mobility & the PI(4,5)P2-dependent organization of cell actin. Proc. Natl. Acad. Sci. USA 100, 13964-13969.
Rocheleau, J.V., Edidin, M. and Piston, D.W. 2003. Intrasequence GFP in class I MHC molecules, a rigid probe for fluorescence anisotropy measurements of the membrane environment. Biophys. J. 84, 4078-4086.
Tang Q. and Edidin, M. 2003. Lowering the barriers to random walks on the cell surface. Biophys. J. 84(1) 400-407.
Edidin, M. 2003. The State of Lipid Rafts: from Model Membranes to Cells. Annu. Rev. Biophys. Biomolec. Struct. 32, 257-283.
Spiliotis, E. T., Pentcheva, T. and Edidin, M. 2002. Probing for membrane domains in the endoplasmic reticulum; retention and degradation of unassembled MHC class I molecules. Mol. Biol. Cell 13, 1566-1582.
Pentcheva, T., Spiliotis, E.T. and Edidin, M. 2002. Tapasin is retained in the endoplasmic reticulum by dynamic clustering and exclusion from endoplasmic reticulum exit sites. J. Imunol. 168, 1538-1541.
Fahmy, T., J.G. Bieler, M. Edidin and J. Schneck. 2001. Increased TCR avidity after T cell activation: A mechanism for sensing low-density antigen. Immunity 14, 135-143.
Spiliotis, E.T., H. Manley, M. Osorio, M. C. Zúñiga, and M. Edidin. 2000. Selective Export of MHC Class I Molecules from the ER after Their Dissociation from TAP. Immunity13, 841-851.
Cole Medal of the Biophysical Society, 1979
Meyerhoff Fellowship of the Weizmann Institute, 1981
MERIT Award, National Institutes of Health, 1988
Fellow of University College London (England), 2004
Doctor, Honoris Causa, Debrecen University (Hungary), 2004
Fellow, American Association for the Advancement of Science (AAAS), 2006
University of Chicago Alumni Association, Professional Achievement Award, 2009
Fellow of the Biophysical Society, 2010