Deborah Yablonski, PhD
Senior Lecturer in Molecular Pharmacology
PhD, 1996 - The Hebrew University, Jerusalem
Immune cell signal transduction
The adaptive immune system includes T and B lymphocytes, which help fight viral and other infections. To function properly, lymphocytes must respond appropriately to multiple extracellular cues, such as chemokines and antigens. Chemokines attract the cells to lymphoid organs and sites of inflammation throughout the body through a process of directed migration known as chemotaxis. Once at the site of action, T cells respond to foreign antigens, which are recognized by the T cell antigen receptor. In the T Cell Signaling Laboratory, we combine genetic and biochemical research approaches to illuminate the intracellular regulatory pathways that are used by the cell to interpret and respond to these extracellular cues. Our ongoing research illuminates the mechanisms used by an adaptor protein, SLP-76, to mediate T cell responses to antigen. A separate research project revealed the role played by p21-activated kinase (Pak) in regulating cytoskeletal events that are required for chemokine-induced migration across restrictive barriers. In addition, mutant cell lines that are selectively defective in this process are being investigated to identify currently unknown cellular elements that enable cell migration.
Dynamic changes in cytoskeletal structures allow migrating T cells to penetrate through restrictive barriersIn resting T cells (left illustration), cytoskeletal structures, composed of actin, vimentin and microtubules, maintain cell shape and rigidity. Chemokines bind to cell surface receptors (such as CXCR4), and induce dramatic changes in cell shape that allow cells to migrate through restrictive openings. This process is associated with a reorganization of cytoskeletal structures and increase in acto-myosin-mediated contractility (right illustration). The signaling pathways mediating these events are a topic of research in the Yablonski laboratory.
Beach, D., Gonen, R., Bogin, Y., Reischl, I. G., Yablonski, D. 2007. Dual role of SLP-76 in mediating T cell receptor-induced activation of phospholipase C-γ. J Biol Chem 282, 2937-2946.
Bogin, Y., Ainey, C., Beach, D., Yablonski, D. 2007. SLP-76 mediates and maintains activation of the Tec family kinase ITK via the T cell antigen receptor-induced association between SLP-76 and ITK. Proc Natl Acad Sci U S A 104, 6638-6643.
Volinsky, N., Gantman, A., Yablonski, D. 2006. A Pak- and Pix-dependent branch of the SDF-1α signalling pathway mediates T cell chemotaxis across restrictive barriers. Biochem J 397, 213-222.