Neetu Gupta, PhD
Associate Staff
Director, Center of Excellence in Lymphoid Malignancies Research
Email: [email protected]
Location: Cleveland Clinic Main Campus
Research
B lymphocytes are a type of blood cell that perform a very important task, to make antibodies that neutralize infectious agents. Our overarching goal is to identify specific aspects of B cell biology that can be targeted to develop new treatment strategies against B cell malignancies and autoimmunity. We focus on activation signals transmitted inside B cells that enable protective immunity, and checkpoints that are critical for preventing B cells from becoming pathogenic.
Biography
Neetu Gupta, PhD, is Associate Staff in the Department of Inflammation and Immunity at the Cleveland Clinic, and Associate Professor of Molecular Medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University. Dr. Gupta's basic research aims to identify mechanisms of B cell development, activation and antibody production, focusing specifically on the role of cytoskeletal proteins as regulators of membrane dynamics, signal transduction and subcellular compartmentalization. Dr. Gupta serves as the Director of the Cleveland Clinic Center of Excellence in Lymphoid Malignancies Research and seeks to foster teamwork, collaboration and cross-pollination of ideas among basic researchers and clinicians engaged in improving clinical care of lymphoma patients. Her research, spanning humoral immunity, autoimmunity, inflammation and cancer immunotherapy, has been published in high impact journals and funded by federal, foundation and institutional grants.
Dr. Gupta earned her graduate degree in Biochemistry from the Indian Institute of Science, Bangalore, and completed postdoctoral training in Immunology at the National Institutes of Health and University of California, San Francisco.
Education & Professional Highlights
Assistant Research Immunologist, University of California, San Francisco, San Francisco, CA, 2004-2007
Postdoctoral Fellow, University of California, San Francisco, San Francisco, CA, 1999-2004
Postdoctoral Fellow, National Institutes of Health, Rockville, MD, 1995-1998
PhD Student, Indian Institute of Science, Bangalore, India, 1990-1995
Masters in Biotechnology, Madurai Kamaraj University, Madurai, India, 1988-1990
Bachelors in Zoology (Honors), University of Delhi, New Delhi, India, 1985-1988
Research
Adaptive Immunity - Cytoskeletal regulation of B cell development, activation and differentiation
We investigate molecular mechanisms of B cell activation that regulate humoral immunity and pathogenesis of B cell-mediated diseases. Dynamic remodeling of the B cell membrane and the actin cytoskeleton facilitates subcellular organization of key signaling proteins, enabling B cells to become activated in response to antigen, differentiate and generate pathogen-neutralizing antibodies. We employ high resolution live cell imaging, quantitative systems biology methods and genetic knockouts in mice to investigate the regulation of B cell function by cytoskeletal proteins such as Ezrin, a member of the Ezrin-Radixin-Moesin (ERM) family of membrane-cytoskeleton linker proteins, and unconventional myosin family proteins. Our studies are providing new insights into the molecular and cellular mechanisms that restrict B cell activation and differentiation, and thereby prevent autoimmunity.
Immuno-Oncology - Mechanisms and biomarkers of CAR T-cell function
As a member of the Center of Excellence in Lymphoid Malignancies Research at the Cleveland Clinic we are actively engaged in understanding the basis of resistance and relapse in aggressive B cell lymphomas and developing novel small molecule and cellular immunotherapies to improve clinical care of lymphoma patients. We are currently identifying the mechanisms and biomarkers of response and acute/chronic toxicities in lymphoma patients treated with CAR T-cells. We expect to apply the knowledge gained from our bed-to-bench investigations to bring improved and customized treatment strategies back to the patients.
Our Team
Selected Publications
SELECTED PEER-REVIEWED PUBLICATIONS
Jalota, A., Hershberger, C.E., Patel, M., Mian, A., Aiman, F., Khademi, G., Rotroff, D., Hill, B., Gupta, N. 2023. Host metabolome predicts the severity and onset of acute toxicities induced by CAR T-cell therapy. Blood Adv. 7:4690-4700.
Aysola, V., Abd, C., Kuo, A.H., and Gupta, N. 2022. Ezrin promotes antigen receptor diversity during B cell development by supporting immunoglobulin heavy chain variable gene recombination. ImmunoHorizons. 6:722-729.
Cheung, M., Enyindah-Asonye, G., Matsui, K., Kosik, I., Dvorina, N., Baldwin III, W.M., Yewdell, J., and Gupta, N. 2021. Myosin 18A is a novel checkpoint regulator in B cell differentiation and antibody-mediated immunity. J Immunol. Cutting Edge, 206:2521-2526.
Tang, J., Xiao, Y., Lin, G., Guo, H., Deng, H-X., Tu, S., Langdon, W., Yang, H., Tao, L., Li, Y., Gupta, N.*, and Zhang, J*. 2021. Tyrosine phosphorylation of NLRP3 by Src Family Protein Tyrosine Kinase Lyn Suppresses NLRP3 inflammasome activation. Sci Signal., 14, eabe3410. *Co-senior authors.
Proudfit, A., Bhunia, N., Pore, D., Parker, Y., Lindner, D.L., and Gupta, N. 2020. Pharmacologic inhibition of ezrin phosphorylation is a novel therapeutic strategy in rhabdomyosarcoma. Sarcoma, doi: 10.1155/2020/9010496. eCollection 2020.
Pore, D., Huang, E., Dejanovic, D., Parameswaran, N., Cheung, M. and Gupta, N. 2018. Deletion of Ezrin in B cells of Lyn-deficient mice downregulates lupus pathology. J. Immuol. Cutting Edge, 201(5):1353-1358.
Enyindah-Asonye, G., Li, Y., Xin, W., Singer, N.G., Gupta, N., Fung, J., and Lin., F. 2017. CD6 receptor regulates intestinal ischemia/reperfusion-induced injury by modulating natural IgM-producing B1a cell self-renewal. J. Biol. Chem. 292(2):661-671.
Pore, D., Matsui, K., Parameswaran, N. and Gupta, N. 2016. Ezrin regulates inflammation by limiting B cell interleukin-10 production. J. Immunol. Cutting Edge,, 196(2):558-62.
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, 29:1857-1867.
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.
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.
Gupta, N., Wollscheid, B., Watts, J., Scheer, B., Aebersold, R.A., and DeFranco, A.L. 2006. Quantitative proteomic analysis of B cell lipid rafts reveals a role for ezrin in the regulation of antigen receptor-mediated lipid raft dynamics. Nat. Immunol. 7:625-633.
Gupta, N., and DeFranco, A.L. 2003. Visualizing lipid raft dynamics and early signaling events during antigen receptor-mediated B cell activation. Mol. Biol. Cell. 14:432-443.
Gupta, N., Scharenberg, A. M., Fruman, D. A., Cantley, L. C., Kinet, J-P., and Long, E. O. 1999. The SH2-containing inositol phosphatase (SHIP) recruits the p85 subunit of phosphatidylinositol-3 kinase during FcγRIIb1-mediated inhibition of B cell receptor signaling. J. Biol. Chem. 274:7489-94.
Gupta, N., Scharenberg, A. M., Burshtyn, D. N., Wagtmann, N., Lioubin, M. N., Rohrschneider, L. R., Kinet, J-P., and Long, E. O. 1997. Negative signaling pathways of the killer cell inhibitory receptor and FcRIIb1 require distinct phosphatases. J. Exp. Med. 186:473-478.
Gupta, N., Martin, B.M., Metcalfe, D.D., and Subba Rao, P.V. 1996. Identification of a novel hydroxyproline-rich glycoprotein as the major allergen in Parthenium pollen. J. Allergy. Clin. Immunol. 98:903-912.
REVIEW ARTICLES
Gupta, N., and DeFranco AL. 2007. Review: Lipid rafts and B cell signaling. Semin. Cell Dev. Biol. 18:616-626.2.
Viola, A., and Gupta, N. 2007. Review: Tether and Trap: Regulation of membrane raft dynamics by actin binding proteins. Nat. Rev. Immunol. 7:889-896.3.
Parameswaran, N. and Gupta, N. 2013. Re-defining ERM function in lymphocyte activation and migration. Immunol. Rev. (Special Issue: The Cytoskeleton), 256:63-79.4.
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.
Careers
We are always looking for motivated, passionate and curious individuals!
- Get exposure to basic and translational research in a mentoring environment
- Let us help you advance your career in immunology and immuno-oncology
- Help us innovate and discover (a) how the B cell antigen receptor repertoire is generated, (b) what cellular processes the cytoskeleton influences to regulate antibody responses and prevent pathogenesis, and (c) mechanisms and biomarkers of response and toxicities to CAR T-cells in patients with aggressive B cell lymphomas
- Join our multinational, multicultural, multiethnic team
- Develop critical thinking skills while interacting with peers at all learning levels, including high school, undergraduate, graduate and medical students, and postdoctoral research and clinical fellows
- Diversity, equity and inclusion are what we practice in all our interactions, every day!
Research News
Dr. Gupta and her team have uncovered a novel role for the protein Myo18A in restricting B cell antibody responses, indicating that this protein controls adaptive immunity