DESCRIPTION Of RESEARCH
We investigate molecular mechanisms of B cell activation that regulate humoral immunity and pathogenesis of B cell-mediated diseases. B cells migrate in and out of circulation and lymphoid tissues, and respond to environmental cues by recognizing antigens and engaging with other components of the immune system. This requires them to undergo considerable morphological, molecular and cytoskeletal reorganization. Dynamic remodeling of the B cell membrane and the actin cytoskeleton facilitates subcellular organization of key signaling proteins, enabling B cells to accomplish their various functions. We employ super-resolution live cell imaging, quantitative proteomics and genetic knockouts in mice to investigate the role of membrane-cytoskeleton remodeling proteins in regulating B cell function. We have discovered that Ezrin, a member of the Ezrin-Radixin-Moesin (ERM) family of membrane-cytoskeleton linkers, regulates multiple facets of B cell function, such as proliferation, differentiation, migration, and antibody production. We are currently investigating the role of membrane-cytoskeleton remodeling proteins in pathogenesis associated with B cell autoimmunity and malignancy.
Debasis Pore, Ph.D., Postdoctoral Fellow
Emily Huang, M.S., Research Technician
Ryan Kocevar, Summer Intern
Sarah Veatch, Ph.D., University of Michigan
Chao-Yie Yang, Ph.D., University of Michigan
Clark Distelhorst, M.D., Case Western Reserve University
Brian Hill, M.D., Ph.D., Hematology and Medical Oncology, CCF
Mitchell Smith, M.D., Hematology and Medical Oncology, CCF
Eric Hsi, M.D., Clinical Pathology, CCF
James Phillips, Ph.D., Translational Hematology and Oncology Research, CCF
Daniel Lindner, Ph.D., Translational Hematology and Oncology Research, CCF
B lymphocytes are a type of blood cell that perform a very important task, which is to make antibodies that clear infections. In my lab we study how activation signals are transmitted inside B cells, so that we can design better ways to protect ourselves. Under certain circumstances, B cells either grow too much or make antibodies against our self proteins. This can lead to B cell cancers and diseases such as lupus. We are also exploring aspects of B cell function that can be targeted to develop new treatment strategies against these diseases.
Selected Recent Publications
Pore, D., Bodo, J., Danda, A., Yan, D., Phillips, J.G., Lindner D.L., Smith, M.R., Hill, B.T., Hsi, E., and Gupta, N. 2015. Identification of Ezrin-Radixin-Moesin proteins as novel regulators of pathogenic B cell receptor signaling and tumor growth in diffuse large B cell lymphoma. Leukemia, doi:10.1038/leu.2015.86.
Pore, D. and Gupta, N. 2014. The ezrin-radixin-moesin family of proteins in the regulation of B-cell immune response. Crit. Rev. Immunol. 35:15-31.
Parameswaran, N. and Gupta, N. 2013. Re-defining ERM function in lymphocyte activation and migration. Immunol. Rev. (Special Issue: The Cytoskeleton), 256:63-79.
Pore, D., Parameswaran, N., Matsui, K., Stone, M.B., Saotome, I., McClatchey, A.I., Veatch, S.L., and Gupta, N. 2013. Ezrin tunes the strength of humoral immunity. J. Immunol., 191:4048-4058.
Parameswaran, N., Enyindah-Asonye, G., Liggett, L., Shah, N., Bagheri, N., and Gupta, N. 2013. Spatial coupling of JNK activation to the B cell antigen receptor by tyrosine-phosphorylated ezrin. J. Immunol. 190:2017-2026.
Kish, D.D., Gorbachev, A.V., Parameswaran, N., Gupta, N., and Fairchild, R.F. 2012. Neutrophil expression of FasL and perforin directs effector CD8 T cell infiltration into antigen-challenged skin. J. Immunol. 189:2191-2202.
Matsui, K., Parameswaran, N., Bagheri, N., Willard, B., and Gupta, N. 2011. Proteomics analysis of the ezrin interactome in B cells reveals a novel association with Myo18aa. J. Proteome Res. 10:3983-3992.
Parameswaran, N., Matsui, K., and Gupta, N. 2011. Conformational switching in ezrin regulates chemokine-induced morphological and cytoskeletal changes required for B cell migration. J. Immunol. 186:4088-4097.