עברית

Prof. Mira Barda-Saad

Telephone
972-3-5317311
Fax
972-3-738-4058
Email
Mira.Barda-Saad@biu.ac.il
Office
The Gonda Medical Diagnostic Research Building (204), 2nd floor, Room 203
Personal Website
Research Categories
Immunology and Cancer Research
CV
Mira Barda-Saad obtained her Ph.D in Molecular Immunology through collaborative research at Bar-Ilan University (BIU) and the Weizmann Institute of Science (WIS). She performed postdoctoral studies at the WIS and later at the NCI/NIH, where she received the Fellows Award for Research Excellence (FARE). Later, she joined the Faculty of Life Sciences at BIU. She was awarded the Taubenblatt Award for Research Excellence in Biomedicine. Prof. Barda-Saad served as the president of the Israeli Immunological Society (IIS) (2017-2020). Currently, she serves as the President of the Federation of the Israel Societies for Experimental Biology (FISEB). Her research focuses on signal transduction mechanisms in immune cells, and specifically, on leukocyte behavior in health and disease.
Research

Our laboratory studies the signal transduction mechanisms of immune cells and follows leukocyte behavior in health and disease. Specifically, we study the molecular mechanisms regulating T and Natural Killer (NK) cell immune response, to modulate their activation state and response under pathophysiological conditions, including cancer, primary immunodeficiencies, and chronic inflammation.

Our specific aims are:

  1. To determine the molecular mechanisms of NK cell immunity, we focus mainly on the negative signaling cascades which inhibit NK cell immune function.
  2. To determine the role of the cytoskeleton in immune cell behavior and malignant cell fate.
  3. To utilize artificial intelligence tools and machine learning platforms to identify small molecule compounds that target signaling cascade/s or protein/s crucial for modulating lymphocyte activity and behavior in pathophysiological conditions.

To perform our research, we apply multidisciplinary techniques, including molecular engineering, nanobiology, biochemical, and biophysical approaches, gene silencing using CRISPR technology, the use of organoids, and in vivo murine model systems. In addition, our studies utilize advanced microscopy techniques (live cell imaging, FRET), and spectral flow cytometry.

Courses

80-385-01 CONTROL MECHANISMS OF THE IMMUNE RESPONSE

Thursday, 12:00-14:00, 2nd semester

 

80-210-01 /10 INTRODUCTION TO IMMUNOLOGY

Sunday, 10:00-12:00, 2nd semester

 

80-930-01 SEMINAR (A)

Friday, 10:00-11:00, 1st semester

 

80-493-01 SEMINAR (B)

Friday, 10:00-12:00, 2nd semester

Publications

LIST OF PUBLICATIONS -PROF. MIRA BARDA-SAAD

  1. Sabag B, Levy M, Kivelevitz J, Dashevsky N, Ben-Shmuel A, Puthenveetil A, Awwad F, and Barda‐Saad M. (2022). Actin Retrograde Flow Regulated by the Wiskott–Aldrich Syndrome Protein Drives Natural Killer Cell Response at the Tumor Microenvironment. Cancers, 14(15):3756. doi: 10.3390/cancers14153756.
  2. Ben-Shmuel A#, Sabag Batel#, Puthenveetil A, Biber G, Levi M, Jubany T, Awaad F, Roy Kumar R, Joseph N, Matalon O, Kivelevitz J, and Barda-Saad M. (2022) Inhibition of SHP-1 activity by PKC-θ regulates NK cell activation threshold and cytotoxicity. eLife, 11:e73282 doi: 10.7554/eLife.73282.
  3. Biber G, Sabag B, Raiff A, Ben-Shmuel A, Puthenveetil A, Benichou J.I.C, Jubany T, Moria Levy M, Killner S, and Barda-Saad M. (2022) Modulation of intrinsic inhibitory checkpoints using nanocarriers to unleash NK cell activity. EMBO Molecular Medicine 14(1):e14073. doi: 10.15252/emmm.202114073.
    The paper was chosen by the editor as the cover of the journal for Jan2022
  4. Biber G, Ben-Shmuel A, Noy E, Joseph N, Puthenveetil A, Reiss N, Levy O, Lazar I, Feiglin A, Ofran Y, Kedmi M, Avigdor A, Fried S, Barda-Saad M. (2021) Targeting WASp Provides an Effective Novel Therapeutic Approach to Suppress Hematopoietic Malignancies. Nature Communications. 12(1):5581. doi: 10.1038/s41467-021-25842-7.
  5. Ben-Shmuel A, Sabag B, Biber G, Barda-Saad M. (2021) The Role of the Cytoskeleton in Regulating the Natural Killer Cell Immune Response in Health and Disease: From Signaling Dynamics to Function. Front Cell Dev Biol. 9:609532. doi: 10.3389/fcell.2021.609532
  6. Biber G., Ben-Shmuel A., Sabag B. and Barda-Saad M. (2020). Actin Regulators in Cancer Progression and Metastases- From Structure and Function to Cytoskeletal Dynamics. International Review of Cell and Molecular Biology. 356:131-196. doi: 10.1016/bs.ircmb.2020.05.006.
  7. Faith Osier, Jenny Ting, John Fraser, Bart Lambrecht, Marta Romano, Ricardo T. Gazzinelli, Karina R. Bortoluci, Dario S. Zamboni, Arne A. Akbar, Jennie Evans, Doug Brown, Kamala D. Patel, Yuzhang Wu, Ana B. Perez, Thomas Kamradt, Mira Barda-Saad, Amiram Ariel, Angela Santoni, Hiroshi Kiyono, Valeriy Chereshnev, Alioune Dieye, M. Mbow, B. Mbengue, M. S. D. Niang, Melinda Suchard (2020). The global response to the COVID-19 pandemic: how have immunology societies contributed? Nature Reviews in Immunology. 20(10):594-602. doi: 10.1038/s41577-020-00428-4.
  8. Ben-Shmuel, A., Biber, G., Batel Sabag and Barda-Saad, M. (2020). Modulation of the SHP-1 checkpoint enhances the anti-tumor activity of engineered NK cells. Cellular and Molecular Immunology. doi:10.1038/s41423-020-0443-6.
  9. Ben-Shmuel, A., Biber, G., and Barda-Saad, M. (2020). Unleashing natural killer cells against tumor specific ligands- the next generation of immunotherapy? Front Immunol. Feb 21; 11:275. eCollection 2020.doi: 10.3389/fimmu.2020.00275.
  10. Ben-Shmuel, A., Sabag, B., Joseph, N., and Barda-Saad, M. (2019). Lymphocyte mechanotransduction- from cytoskeletal dynamics to signaling cascades. Journal of leukocyte biology, 105(6):1261. doi: 10.1002/JLB.MR0718-267R.
  11. Ben-Shmuel, A., Joseph, N., and Barda-Saad, M. (2018). Commentary: Integrins Modulate T Cell Receptor Signaling by Constraining Actin Flow at the Immunological Synapse. Frontiers in Immunology, ;9:2110. doi: 10.3389/fimmu.2018.02110. eCollection 2018. Single Corresponding Author
  12. Avishay, E., Avishai S., Matalon, O., Brusilovsky, M., Radinsky, O., Gershoni-Yahalom,O., Mandelboim, O., Dye, J.M., Barda-Saad, M., Lobel,L., and Porgador, A. (2018). Recognition of Ebola-Glycoprotein Expressing Target Cells by Natural Killer Cells. Frontiers in Immunology 9:1428. doi: 10.3389/fimmu.2018.01428.
  13. Matalon, O., Ben-Shmuel, A., Kivelevitz, J., Sabag, B., Fried, S., Joseph, N., Noy, E., Biber, G., and Barda-Saad, M. (2018). Actin retrograde flow controls NK cell response by regulating the conformation state of SHP-1. EMBO J. 37(5): pii: e96264. doi: 10.15252/embj.201696264.
  14. Halle-Bikovski, A. †, Fried, S. †, Biber, G., Rozentur-Shkop, E., Shaked, H., Joseph, N., Barda-Saad, M. #, and Chill H.J.# (2017) A complementary structural and in-vivo view of the chaperone function of WASp-interacting protein. ACS Chemical Biology, 13(1):100-109, doi: 10.1021/acschembio.7b00486.  
    †, # These authors contributed equally to this work and are the corresponding authors.
  15. Yom-Tov, G., Barak, R., Matalon, O.,  Barda-Saad, M., Guez-Haddad, J., and Opatowsky, Y. (2017). Robo Ig4 is a Dimerization Domain. J. Mol. Biol. 429(23):3606-3616. doi: 10.1016/j.jmb.2017.10.002.
  16. Joseph, N., Biber, G., Fried, S. Reicher, B., Levy, O., Sabag, B., Noy, E. and Barda-Saad, M. (2017) A conformational change within the WAVE2 complex regulates its degradation following cellular activation. Scientific Reports, 7:44863. doi: 10.1038/srep44863
  17. Matalon. O. and Barda-Saad, M. (2016). Cbl ubiquitin ligases mediate the inhibition of natural killer cell Activity. Communicative & Integrative Biology 9:6. doi: 10.1080/19420889.2016.1216739.
  18. Matalon, O., Fried S., Ben-Shmuel, A., Pauker, M.H., Joseph, N., Keizer, D., Piterburg, M. and Barda-Saad M. (2016) Dephosphorylation of the adaptor LAT and phospholipase C–g by SHP-1 inhibits natural killer cell cytotoxicity. Science Signaling, 9: ra54.
    The paper was chosen as the focus of the journal and was overviewed by Kerry S. Campbell. Suppressing the killer instinct. Sci. Signal. 9, fs8 (2016).
  19. Ziv-Av, A., Giladi, ND., Lee, HK., Cazacu, S., Finniss, S., Xiang, C., Pauker, H.M., Barda-Saad, M., Poisson, L. and Brodie, C. (2015) RTVP-1 regulates glioma cell migration and invasion via interaction with N-WASP and hnRNPK. Oncotarget, 6:19826.
  20. Elazari-Shalom, H., Shaked, H., Esteban-Martin, S., Salvatella, X., Barda-Saad, M. and Chill, J. (2015) New insights into the role of the disordered WIP N-terminal domain revealed by NMR structural characterization. FEBS Journal, 282:700.
  21. Pauker, MH., Reicher, B., Wortzel1, I., Joseph, N., Jakubowicz, S., Perl, O., and Barda-Saad, M. (2014) WASp Family Verprolin-Homologous Protein-2 (WAVE2) and Wiskott-Aldrich Syndrome Protein (WASp) Engage in Distinct Downstream Signaling Interactions at the T Cell Antigen Receptor Site. JBC, 289:34503.
  22. Joseph, N., Reicher, B., Ahuvit D., Matalon, O., and Barda-Saad, M. (2014) Ubiquitylation-dependent downregulation of Nck regulates its functional activity. FEBS Lett. 588:3808.
  23. Fried, S., Matalon, O., Noy, E., and Barda-Saad, M. (2014) WIP: More than a WASp interacting protein. Journal of leukocyte biology, 96:713.
  24. Borodianskiy-Shteinberg, T., Kalt, I., Kipper, S., Katz, S., Pauker, H. M., Barda-Saad, M., Gerber, D., and Sarid, R. (2014) The Nucleolar PICT-1/GLTSCR2 Protein Forms Homo-Oligomers. Journal of Molecular Biology, 426:2363.
  25. Fried, S., Pauker, M. H., Reicher, B., Eliyahu, S., Matalon, O., Noy, E., Chill, J., and Barda-Saad, M. (2014) Triple-color FRET analysis reveals conformational changes in the WIP-WASp actin-regulating complex.  Science Signaling. 7:ra60. 
    The paper was chosen as the Editor’s choice.
  26. Joseph, N., Reicher, B. and Barda-Saad, M. (2013) The calcium feedback loop and T-cell activation: how the cytoskeleton networks control intracellular calcium levels. Biochimica et Biophysica Acta (BBA) – Biomembranes, 105:481-93.
  27. Klieger, Y., Almogi-Hazan, O., Ish-Shalom, E., Pato, A., Pauker, H.M., Barda-Saad, M., Wang, L. and Baniyash, M. (2013) Unique ζ-chain motifs mediate a direct TCR-actin linkage critical for immunological synapse formation and T-cell activation. Eur. J. Immunol. 44:58.
  28. Haba, N.Y., Gross, R., Novacek, J., Shaked, H., Zidek, L., Barda-Saad, M. and Chill, J.H. (2013) NMR determines transient structure and dynamics in the disordered C-terminal domain of WASp interacting protein. Biophys. J. 105:481.
  29. Reicher, B., Matalon, O. and Barda-Saad, M. (2013) WASp function in T cell signaling microclusters. Immunol. Rev. 256:10-29.
  30. Noy, E., Fried, S. Matalon, O. and Barda-Saad M. (2012) WIP remodeling actin behind the scenes: How WIP reshapes immune and other functions. Int. J. Mol. Sci. 13:7629.
  31. Reicher, B., Perl, O., Matalon, O. and Barda-Saad, M. (2012) WASp and WAVE proteins: from structure, through function, to clinical aspects. Review, J. Clin. Cell. Immunol., doi: 10.4172/2155-9899.S12-001.
  32. Ovadia, A., Livneh, A., Feld, O., Ben-Zvi, I., Kukuy, E., Kivity, S., Lidar, M., Barda-Saad, M. and Shinar, Y. (2013) T helper 17 polarization in familial Mediterranean fever. Genes & Immun. 1-5. doi: 10.1038/gene.2013.6.
  33. Reicher, B., David, A., Perl, O. and Barda-Saad, M. (2012) Ubiquitylation-dependent negative regulation of the Wiskott-Aldrich Syndrome protein (WASp) complex. Mol. Cell. Biol. 32:3153.
  34. Pauker, H.M., Hassan, N. Noy, E. Reicher, B. and Barda-Saad, M. (2012) Development of a novel triple color FRET technique for the investigation of the molecular interactions regulating T-cell activation. Science Signaling. 5(221):rs3 (cover).
  35. Noy, E., and Barda-Saad, M. (2011) Invited Book’s Chapter: Stoichiometry of Signaling Complexes in Immune Cells: Regulation by the Numbers. Chapter 9 in: Stoichiometry and Research- The importance of quantity in biomedicine (Online book edition). Ed: Alessio Innocenti, InTech publications, Inc.
  36. Reicher, B., and Barda-Saad, M. (2011) Invited Book’s Chapter: The molecular mechanisms of actin regulatory proteins. Chapter 6 in: Actin: Structure, Functions and Disease (Online book edition). Eds: Victoria A. Consuelas and Daniel J. Minas. Nova Science Publishers, Inc.
  37. Pauker, H.M., Reicher, B., Fried, S., Perl, O., and Barda-Saad, M. (2011) Functional cooperativity between the proteins Nck and ADAP is fundamental for actin reorganization following TCR activation. Mol Cell Biol. 31:2653-2666. 
  38. Hazani, M. and Barda-Saad, M. (2011) Studies of novel interactions between Nck and VAV SH3 domains. Comm. Integ. Biol. 4:175-177.
  39. Reicher, B. and Barda-Saad, M. (2010) Multiple Pathways leading from the T cell antigen receptor to the actin cytoskeleton network. FEBS Lett. 584:4858-4864.
  40. Barda-Saad, M, Shirasu, N., Pauker M.H, Hasan, N., Perl, O., Balbo, A., Yamaguchi, H., Houtman, J., Appella, E., Schuck, P. and Samelson, LE. (2010) Cooperative interactions at the SLP-76 complex are critical for T-cell signaling and actin polymerization. EMBO J. 29:2315-2328
  41. Shani, N, Rubin-Lifshitz, H., Sccolnick, K., Peretz-Chohen, Y. Shkolnik, K., Shnider, V., Cohen, M., Shav-Tal, Y., Barda-Saad, M. and Zipori D. (2008) Incomplete T cell receptor transcripts encode proteins that target the mitochondrion and induce apoptosis. Blood. 9:3530-3541.
  42. Balagopalan, L., Barr, V.A., Sommers, C.L., Barda-Saad, M., Goyal, A., Isakowitz, M.S. and Samelson, L.E. (2007). c-Cbl mediated regulation of LAT-nucleated signaling complexes. Mol. Cell. Biol. 27:8622-8636.
  43. Houtman, J., Yamaguchi, H., Barda-Saad, M., Bowden, B., Schuck, P., Appella, E., and Samelson, LE. (2006). Oligomerization of intracellular signaling complexes by the multipoint binding of the adapter protein Grb-2 to both LAT and Sos1. Nature Struct. Mol. Biol. 13:798-805.
  44. Barr, V.A., Balagopalan-Bhise, L., Barda-Saad, M., Polishchuk, R., Boukari, H.,Bunnell, S.C., Bernot, K.M., Toda, Y., Nossal, R., and Samelson, L.E. (2006). T-cell antigen receptor-induced signaling complexes: Internalization via a cholesterol-dependent endocytic pathway. Traffic 7:1143-1163.
  45. Braiman, A., Barda-Saad, M. and Samelson, L.E. (2006). Recruitment and activation of PLCg1in T-cells: a new insight into old domains. EMBO J. 25:774-84.
  46. Barda-Saad, M., Braiman, A., Titerence, R., Barr, V. and Samelson, L.E. (2006). T cell antigen receptor engagement induced cytoskeleton re-organization. CCR Frontiers in Science (Published by the National Cancer Institute’s Center for Cancer Research, NIH).
  47. Houtman, J., Barda-Saad, M. and Samelson, L.E. (2005). How to examine multiprotein signaling complexes from all angles: The use of complementary techniques to characterize complex formation at the adapter protein LAT. FEBS J. 272:5426-35.
  48. Houtman, J., Houghtling, R., Barda-Saad, M., Toda, Y., Schwartzberg, PL., and Samelson, LE. (2005). Early phosphorylation kinetics of proteins involved in proximal T-cell receptor-mediated signaling pathways. J. Immunol. 15:2449-2458.
  49. Barda-Saad, M.,Braiman, A.,Titerence, R.,  Bunnell, S.C.,  Barr, V.A., and Samelson, L.E. (2005) Dynamic molecular interactions linking the T cell antigen receptor to the actin cytoskeleton. Nature Immunology 6:80-89.
  50. Shoham, T., Parameswaran, R., Shav-Tal, Y., Barda-Saad, M., and Zipori D. (2003). The Mesenchymal Stroma Negatively Regulates B Cell Lymphopoiesis through the Expression of Activin A. Ann. N Y Acad. Sci. 996:245-260.
  51. Barda-Saad, M., Shav-Tal, Y., Rozenszajn, L.A., Cohen, M., Zauberman, A., Karmazyn, A., Parameswaran, R, Schori, H, Ashush, H., Ben-Nun, A. and Zipori D. (2002). The mesenchyme expresses T cell receptor mRNAs: relevance to cell growth control. Oncogene 21:2029-36.
  52. Shoham, T., Sternberg, D., Brosh, N., Barda-Saad, M. and Zipori D. (2001). The promotion of plasmacytoma growth by mesenchymal stroma is antagonized by basic fibroblast growth factor induced activin A. Leukemia 15:1102-10.
  53. Zipori, D., Barda-Saad, M. (2001). Role of activin A in negative regulation of normal and tumor B lymphocytes. J. Leukoc. Biol. 69:867-73.
  54. Ashush, H., Rozenszajn, LA, Blass, M., Barda-Saad, M., Azimov, D., Radnay, J., Zipori, D. and Rosenschein U. (2000). Apoptosis induction of human myeloid leukemic cells by ultrasound exposure. Cancer Res. 60:1014-20.
  55. Barda-Saad, M., Rozenszajn, LA, Ashush, H., Shav-Tal, Y., Ben-Nun, A. and Zipori, D. (1999). Adhesion molecules involved in the interactions between early T-cells and mesenchymal bone marrow stromal cells. Exp Hematol. 27: 834-44.
  56. Yu, S., Wang, S.L., Zhang, H.W., Huang, Z., Abel, L., Barda-Saad, M., Zipori, D. and Globerson, A. (1998). Effect of aging on the expression of surface antigen in mouse thymocytes. Acta Zoologica Sinica, 44:466-474.
  57. Barda-Saad, M., Zhang, A.S., Zipori, D. and Rozenszajn, L.A. (1997). Adhesion of thymocytes to bone marrow stroma cells: regulation by bFGF and IFN-gamma Stem Cells 15: 229-36.
  58. Barda-Saad, M., Zipori, D., Globerson, A., Zhang, A.S. and Rozenszajn, L.A. (1996). Selective adhesion of immature thymocytes to bone marrow stromal cells: relevance to T cell lymphopoiesis. Exp Hematol. 24: 386-91.
     
    Chapters in Books
     
  59. Reicher, B., and Barda-Saad, M. (2011) Invited Book Chapter: The molecular mechanisms of actin regulatory proteins. Chapter 6 in: Actin: Structure, Functions and Disease (Online book edition). Eds: Victoria A. Consuelas and Daniel J. Minas. Nova Science Publishers, Inc.
  60. Elad, N., Reicher, B. and Barda-Saad, M. (2011) Invited Book Chapter: Stoichiometry of Signaling Complexes
    in Immune Cells: Regulation by the Numbers. Chapter 9 in: Stoichiometry and Research- The importance of quantity in biomedicine (Online book edition). Ed: Alessio Innocenti, InTech publications, Inc.


    Patents
     
  • PCT/IL02/00130- #20040259196, T Cell Receptor Variants Expressed in Mesenchymal Cells and Uses Thereof.
  • PCT/IL02/00129 - #20040101931, Immunoglobulin Superfamily Variants Expressed in Mesenchymal Cells and Therapeutic Uses Thereof.
  • #20070196365 – Immunoglobulin Heavy Chain Variants Expressed in Mesenchymal Cells and Therapeutic Uses Thereof.
  • PCT/CD25-P1330 Liposomes For Modulating Wiskott-Aldrich Syndrome Protein. Europe No. 14808354.6. Israel No. 242908 United States No. 14/895,734 .
  • PCT/02509126-97-01 September 2017: WASp-Protecting Small Molecules, Compositions, Methods and Uses Thereof in the Treatment of Innate and Acquired Immune-Related Disorders or Conditions.
  • PCT/02374510-42-01 January 2018: Compositions and Methods for Controlling Natural Killer Cell Activation and Function.
  • PCT/62797373 January 2019: Combinations, nanoparticles and methods for controlling natural killer cell activation and function.

Last Updated Date : 15/02/2023