Prof. Mira Barda-Saad
Cancer and Tumor Immunology; Natural Killer (NK) Cells and Lymphocyte Biology; Cancer Immunotherapy; Immune Cell Signaling; Lymphocyte Reprogramming; Immune Mechanobiology and Mechanotransduction; Tumor Microenvironment; Cytoskeleton and WASp; Immunological Synapse; Intracellular Immune Checkpoints; RNA Therapeutics; Nanoparticle-Based Drug Delivery; Precision Immunotherapy.
CV
Research
Laboratory of Molecular Applied Immunology
Our laboratory investigates the molecular and cellular mechanisms that regulate immune-cell function, aiming to understand how immune cells sense their environment, integrate signals, make functional decisions, and mount effective responses against cancer. Our research in cancer and tumor immunology focuses on deciphering signaling networks in lymphocytes, particularly natural killer (NK) cells and T cells, and on understanding how intracellular signaling, cytoskeletal organization, and immunological synapse formation collectively shape immune-cell function.
Our studies have uncovered mechanisms through which signaling proteins, phosphatases, transcription factors, intracellular immune checkpoints, and the actin cytoskeleton determine immune-cell activation thresholds and cytotoxic capacity. This research includes investigating key cytoskeletal regulators such as WASp and their roles in immune-cell signaling and function. In recent years, a major focus of our research has been to understand how the tumor microenvironment alters these regulatory mechanisms, progressively driving NK cells toward dysfunction and exhaustion. Another central research direction is immune-cell mechanobiology and mechanotransduction: understanding how immune cells sense and translate physical properties of their environment, including tumor tissue stiffness, into intracellular signals that influence their function.
Alongside our fundamental research, we develop innovative strategies for lymphocyte reprogramming to restore the anti-tumor activity of dysfunctional immune cells. These approaches target intracellular signaling and regulatory pathways and employ advanced RNA therapeutics and nanoparticle-based drug delivery systems. By integrating immunology, cell biology, biophysics, and nanomedicine, our research bridges fundamental mechanistic discoveries with the identification of novel therapeutic targets and the development of precision immunotherapy strategies for cancer.
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
Selected Publications
Sabag B, Puthenveetil A, Levy M, et al., Barda-Saad M. Dysfunctional natural killer cells can be reprogrammed to regain anti-tumor activity. The EMBO Journal. 2024;43:2552–2581. doi:10.1038/s44318-024-00094-5.
Identifies Egr2 and DGKα as key regulators of NK-cell dysfunction and demonstrates that nanoparticle-based reprogramming can restore anti-tumor activity in experimental models, opening new avenues for cancer immunotherapy
Biber G, Sabag B, Raiff A, et al., Barda-Saad M. Modulation of intrinsic inhibitory checkpoints using nano-carriers to unleash NK cell activity. EMBO Molecular Medicine. 2022;14:e14073. doi:10.15252/emmm.202114073. PubMed
Develops a lipid nanoparticle-based delivery system that silences intracellular inhibitory checkpoints in NK cells, enhancing their ability to eliminate tumors and offering a potential strategy for cancer immunotherapy.
Biber G, Ben-Shmuel A, Noy E, et al., Barda-Saad M. Targeting the actin nucleation promoting factor WASp provides a therapeutic approach for hematopoietic malignancies. Nature Communications. 2021;12:5581. doi:10.1038/s41467-021-25842-7.
Identifies a small molecule that promotes WASp degradation and disrupts actin-dependent processes in hematopoietic malignancies, demonstrating a potential therapeutic strategy that spares healthy cells in the tested models.
Ben-Shmuel A, Biber G, Sabag B, Barda-Saad M. Modulation of the intracellular inhibitory checkpoint SHP-1 enhances the antitumor activity of engineered NK cells. Cellular & Molecular Immunology. 2021;18:1314–1316. doi:10.1038/s41423-020-0443-6. Nature
Demonstrates that targeting the intracellular inhibitory checkpoint SHP-1 enhances the anti-tumor activity of engineered NK cells, supporting strategies to improve NK-cell-based cancer immunotherapy.
Matalon O, Ben-Shmuel A, Kivelevitz J, et al., Barda-Saad M. Actin retrograde flow controls natural killer cell response by regulating the conformation state of SHP-1. The EMBO Journal. 2018;37:e96264. doi:10.15252/embj.201696264.
Reveals how actomyosin retrograde flow regulates NK-cell cytotoxicity by altering SHP-1 conformation through its interaction with β-actin, establishing a mechanistic link between cytoskeletal forces and immune-cell signaling.
Ben-Shmuel A, Biber G, Barda-Saad M. Unleashing Natural Killer Cells in the Tumor Microenvironment—The Next Generation of Immunotherapy? Frontiers in Immunology. 2020;11:275. doi:10.3389/fimmu.2020.00275. Review. Frontiers
Reviews mechanisms by which tumors evade NK-cell immune surveillance and examines therapeutic strategies, including antibody-based approaches and modulation of the tumor microenvironment, to enhance NK-cell-mediated cancer immunotherapy.
Barda-Saad M, Braiman A, Titerence R, Bunnell SC, Barr VA, Samelson LE. Dynamic molecular interactions linking the T cell antigen receptor to the actin cytoskeleton. Nature Immunology. 2005;6:80–89. doi:10.1038/ni1143. Nature
Characterizes the dynamic recruitment and interactions of signaling and actin-regulatory proteins during T-cell activation, revealing how T-cell receptor signaling is coordinated with actin cytoskeleton remodeling.
Osier F, Ting JPY, Fraser J, et al., Barda-Saad M, et al. The global response to the COVID-19 pandemic: how have immunology societies contributed? Nature Reviews Immunology. 2020;20:594–602. doi:10.1038/s41577-020-00428-4.
Brings together perspectives from international and national immunology society leaders on their responses to the COVID-19 pandemic, highlighting the contributions of scientific societies to research coordination, communication, and public health.
Chapters in Books
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.
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.
Media
- “It’s Only a Matter of Time Before We Find a Cure”: Groundbreaking Israeli Research Offers New Hope for Cancer Treatment | Dangoor Center for Personalized Medicine, Bar-Ilan University | 2026 | Interview on cancer immunotherapy, immune-cell exhaustion, AI and tumor mechanics.
- חוקרות סרטן בכירות זכו במענק המחקר המצטיין של האגודה למלחמה בסרטן | Israel Cancer Association | 17.02.2025 | Coverage of the Outstanding Research Grant for developing strategies to restore dysfunctional NK cells in solid tumors.
- לעזור לתאי הרג טבעיים להילחם בסרטן | Dangoor Center for Personalized Medicine, Bar-Ilan University | 30.08.2024 | Feature on the EMBO Journal study identifying mechanisms of NK-cell dysfunction and therapeutic reprogramming.
- ננו-חלקיקים מייעלים את המלחמה בסרטן | Bar-Ilan University | 05.08.2024 | Feature on nanoparticle-based strategies for restoring the activity of dysfunctional cancer-fighting NK cells.
- On “Cancer Vaccines” – With Professor Mira Barda-Saad | Dangoor Center for Personalized Medicine Podcast | 2024 | Podcast interview on the immune response to cancer and reprogramming T and NK cells.
Last Updated Date : 12/10/2026