Dr. Barda-Saad's Lab
Head - Immunology and Cancer Research Lab
Dr. Mira Barda-Saad, a returning scientist from the National Cancer Institute at NIH in Maryland, is a Senior Lecturer at the Mina and Everard Goodman Faculty of Life Sciences.
Barda-Saad is currently examining the molecular signaling mechanisms controlling immune cell response with the primary goal of relating this knowledge to pathophysiological conditions of the immune system.
She believes that understanding the dynamic behavior of signaling and cytoskeletal molecules that control immune cell activation is essential for identification of targets relevant for the treatment of cancer, autoimmune diseases and immunodeficiencies.
Unraveling T-Cell Signaling Cascades
The initiation and progression of the immune response depends upon the tight regulation of lymphocyte activation. When the T cell antigen receptor (TCR) binds foreign antigens on antigen-presenting cells (APCs), multiple proteins redistribute to form the immunological synapse.
This binding initiates a signal that must be enhanced and sustained long enough for the T cells to lead to an immune response.
This signal must also be terminated in time to avoid antigen-induced suicide of T cells or T cell tolerance, which leads to multiple pathologies. T-cell activation is associated with a dramatic reorganization of cell surface receptors, cytosolic signaling molecules, and cytoskeletal elements within the immunological synapse. Organization of the synapse and the creation of a tight seal between the T cell and the APC depend on actin polymerization.
Polymerization of actin filaments at the contact site is thought to assist in the amplification and generation of functional immune response. However, the molecular events leading from TCR activation to cytoskeletal rearrangement, and specifically to actin polymerization, are not well established. The primary focus of Barda Saad's research is to unravel the molecular mechanisms that regulate T-cell activation.
The Role of Cytoskeletal Regulatory Proteins in Hematopoietic Malignancies
Barda Saad's team is exploring cytoskeletal regulatory proteins that are exclusively expressed in hematopoietic cells and their role in the motility of these cells. Lymphoma is the third most common cancer in children and the fifth most common in adults, accounting for 53% of annual blood-cancer cases.
The aim of this group's research is to analyze specific alterations in gene expression of invading cells and investigate whether aberrant regulation of this protein expression or function plays a role in the activation, motility and tissue infiltration behavior of malignant lymphoma cells.
While most studies have focused on normal cells, they examine the control of actin reorganization in live cancerous cells, utilizing their expertise to follow the dynamics of protein interactions in living immune cells by using cutting edge microscopy.
Molecular Mechanisms that Control the Natural Killer Cell Response
Barda Saad and her team utilize a similar molecular imaging approach to study natural killer (NK) cells. NK cells are innate immune system lymphocytes that serve as a powerful weapon for early immune defense against viruses and tumors, and their signaling pathways are complex networks of activating and inhibitory interactions.
The mechanism behind their ability to distinguish between harmless self cells and potentially harmful virally infected or malignant target cells, is yet unclear.
One of Barda Saad's research goals is to elucidate the molecular mechanisms regulating the NK cell activation threshold in order to pave the way for developing therapeutic approaches to combat immune disease.
Barda Saad's laboratory has an integrated research program using biochemistry, mutagenesis, siRNA-based gene silencing, recombinant fusion proteins, and high-speed microscopic analysis, including live-cell imaging, to explore lymphocyte signal transduction and the immune response.