Neetu Gupta, Ph.D.
Assistant Staff

Neetu Gupta, Ph.D.

Assistant Staff

  • Department of Immunology
  • Lerner Research Institute (NB30)
  • The Cleveland Clinic Foundation
  • 9500 Euclid Avenue
  • Cleveland, Ohio 44195
  • (216) 444-7455
  • (216) 444-9329

Other Academic Affiliations

  • Assistant Professor, Cleveland Clinic Lerner College of Medicine of CWRU
  • Trainer, Immunology Training Program, Department of Pathology, CWRU
  • Adjunct Faculty, BGES, Cleveland State University
  • Associate Member, Case Comprehensive Cancer Center

Areas of General Research Interest

Lymphocyte activation; Signal transduction; Membrane-cytoskeletal dynamics; Lymphoma/Leukemia; Autoimmunity.

Current program

  • Antigen receptor signaling at the membrane-cytoskeletal interface in B cells.

FUNDING

Ongoing Research Support

  • R01 Research Grant, NIAID, NIH (2009-2013).
  • Supplement Grant Title: Regulation of B Cell Function by Membrane-Cytoskeletal Remodeling
    PI: Neetu Gupta Student: Gospel Enyindah-Asonye
    Funding Agency: Supplemental Grant to Promote Diversity in Health Related Research (2011-2013)
  • Investigator Award, Cancer Research Institute (2008 – 2012).

Completed Research Support:

  • K01 Career Development Award, NIDDK, NIH (2004 – 2010).
  • Concept Award, Breast Cancer Research Program, Department of Defense (2008-2009).
FigFig

OVERVIEW OF RESEARCH

The B cell antigen receptor (BCR) serves key roles in directing the activation of B cells that make antibodies reactive to foreign agents such as pathogens, tumors and transplants, and also in preventing B cells from making antibodies reactive to its own self. Underactive or overactive B cells are often associated with immunodeficiency, cancer and autoimmune disorders. B cell immune response involves communication of signals from the cell’s surface to its core, the nucleus, where gene expression occurs. Simultaneous rearrangement of the B cell membrane and the underlying actin cytoskeleton facilitates dynamic recruitment of key signaling components into signalosomes at the cell surface. An understanding of the molecular mechanisms of antigen receptor signaling are critical for design of better vaccines against infectious agents as well as identification of therapeutic targets in autoimmunity and cancer. In order to probe the molecular mechanisms of B cell activation, we employ a mixture of cutting edge technologies including high definition live cell imaging, intravital in situ imaging, quantitative proteomics, transgenic/knockout mice, as well as standard biochemistry and molecular biology methods.


RECENT FINDINGS

We have demonstrated that BCR cross-linking induces fusion of nanoscale membrane raft units to generate patches that ultimately coalesce into stable, micron-sized rafts. Using systems biology and live cell imaging, we identified ezrin, a member of the ezrin-radixin-moesin (ERM) family, as a regulator of antigen-induced lipid raft coalescence via a conformational switch in its structure. The conformational inactivation occurs upon antigen-induced dephosphorylation of ezrin at the conserved threonine residue in its actin-binding domain.

Using scanning electron microscopy and total internal reflection microscopy (TIRF), we have further shown that a transient switch in the conformation of ezrin from active to dormant is a critical trigger that initiates morphological changes associated with cell polarization, and regulates B cell migration.

Ezrin can also potentially participate in signal transduction via an adaptor function. We have observed that BCR stimulation induces phosphorylation of ezrin on unconserved tyrosine residues, and that mutation of these residues impairs specific signaling pathways in B cell activation. Our data suggest that ezrin has a unique role in antigen-induced signal transduction.

ONGOING RESEARCH DIRECTIONS

We are currently engaged in structure-function analysis of ezrin through in vitro biochemistry and transgenic mouse modeling, as well as high definition live cell imaging. We are also interested in exploring the role of unconventional myosins in B cell development and activation.

Investigators

  • Neetha Parameswaran, Ph.D., Postdoctoral Fellow
  • Debasis Pore, Ph.D., Postdoctoral Fellow
  • Gospel Enyindah-Asonye, Molecular Medicine Graduate Student
  • Alvaro Alvarado, Molecular Medicine Rotation Student

Collaborators

  • Andrea McClatchey, Ph.D., Harvard University
  • Bernd Wollscheid, Ph.D., Swiss Federal Research Institute, Zurich
  • Alex Huang, M.D., Ph.D., Case Western Reserve University
  • Gospel Enyindah-Asonye
  • Molecular Medicine Student
  • Location:NE4-253
  • enyindg@ccf.org
  • (216) 445-4604
  • Ken Matsui Ph.D.
  • Postdoctoral Fellow
  • Location:NE4-253A
  • matsuik@ccf.org
  • (216) 445-4604
  • (216) 444-9329
  • Neetha Parameswaran Ph.D.
  • Post Doctoral Research Fellow
  • Location:NE4-253A
  • paramen@ccf.org
  • (216) 445-4064
  • (216) 444-9329
  • Debasis Pore Ph.D.
  • Postdoctoral Fellow
  • Location:NE4-253
  • pored@ccf.org
  • (216) 445-4604

click on picture for zoom out


Publications

Matsui K, Parameswaran N, Bagheri N, Willard B, Gupta N. 2011 Proteomics analysis of the ezrin interactome in B cells reveals a novel association with Myo18a alpha. J. Proteome Res. 10:3983-3992.

Neetha Parameswaran, Ken Matsui, and Neetu Gupta. 2011. Conformational switching in ezrin regulates morphological and cytoskeletal changes required for B cell chemotaxis. J. Immunol. 186:4088-4097.

Neetha Parameswaran, Twishasri Dasgupta, and Neetu Gupta. 2009. Orchestration of B lymphocyte activation and motility by the ERM protein Ezrin. Proc. Microsc. Microanal. 15 (Suppl 2).

Book Chapters

Neetu Gupta, Anthony L. DeFranco, and Arthur Weiss. Signal transduction by T and B lymphocyte antigen receptors. In Primary Immunodeficiency Diseases, a Molecular and Genetic Approach, 2nd Edition, H. D. Ochs, C. I. E. Smith, and J. Puck, eds ., Oxford Press, Oxford, UK. 2007 .

Journal Links