Prof. Ofer Lider Former Incumbent of The Weizmann League Career Development Chair in Children's Diseases

On July 12, 2004, the department suffered a tragic loss with the untimely passing of Prof. Ofer Lider, z"l. His students and colleagues are devotedly continuing Prof. Lider's outstanding scientific achievments. In addition, Ofer’s family, friends and colleagues have founded Life’s Verse as a non-profit association (Reg. no. 580438984), to encourage other scientists to follow in Ofer’s path. Scientists from the Weizmann Institute of Science, staff members of the Literary Supplement of "Yedioth Ahronoth" and other writers jointly take part in furthering the aims of Life’s Verse on a daily basis. In this vein, Life's Verse is sponsoring an annual literary prize to commemorate unique wedding of science with art, and to encourage scientists to express their creativity in the world of the written word as in the world of nature. So may Ofer’s verse live on. For a glimpse into the richness and creativity that was Ofer, see http://www.lider.name/.

 Research Interests:

Regulation of lymphocyte entry into and behavior in inflamed sites

The process of circulation of lymphocytes from blood to tissues and back to the blood occurs during homeostasis as well as during pathological conditions. In such instances lymphocytes have to migrate through the extracellular matrix (ECM). The nature of the recruiting and directing signals involved in this process, the motility of immune cells, the communication between migrating cells, how the migrating cells sense their environment, the cellular invasion of the sub-endothelial ECM, and the intrinsic regulation, by tissue components and fractions of pro-inflammatory mediators, of the intensity of the inflammatory reaction, are the main topics of our research.

Our major research goals and directions are:

• Cytokines in context:
  We are studying the effects of the interactions between migrating T lymphocytes and ECM ligands, especially those present in inflamed loci; sites where ECM moieties can interact with, and present cytokines and other pro-inflammatory mediators to the migrating leukocytes.

• Feedback regulation of immune reactions by breakdown products of ECM
  We hypothesized that the among the molecule present in the inflammatory milieu should exist some which may signal the termination of the process. We have found that molecular products of enzymatically-treated heparan sulfate of ECM can signal a decrease in the intensity and severity of the inflammatory process. With regard to these enzymatically-released molecules, our efforts are directed toward (i) the development of chemical and biological means for obtaining such modulatory molecules, (ii) their chemical elucidation, (iii) analysis of the immuno-modulatory or immuno-suppressive modes of their action, and (iv) testing their beneficial values in inflammatory reactions in-vivo.

• Feedback regulation of inflammation by naturally occurring enzymatic breakdown products of cytokines
  We assume that both adhesion- and migration-promoting stimuli (i.e. intact cytokines) and suppressive products of inflammatory mediators can be present, although not necessarily simultaneously, within the inflammatory milieu. At the early stages of inflammation, both pro-inflammatory cytokines and ECM-degrading enzymes, such as elastase, may function concomitantly to activate T cells to penetrate tissues. Later, the degradation peptide products of the cytokines, generated by such enzymes, may inhibit T cell migration, inhibit the co-stimulatory effects of inflammatory mediators, and therefore, signal the termination of the inflammatory reaction.

  We have found that elastase degrades IL-2 to yield IL-2 fractions that inhibit IL-2-induced T cell adhesion to ECM and chemotactic migration through ECM barriers. Also, we found the IL-2 binding receptor on T cells, and that certain IL-2 peptides inhibit inflammation in vivo. In the future, we will examine additional breakdown products of cytokines and their regulatory role.

• Real time analysis of integrin-mediated chemotactic migration of T lymphocytes within 3-D extracellular matrix-like gels
  We have developed, together with Dr. Ronen Alon, a novel 3-dimensional gel reconstituted with major ECM glycoproteins to follow the dynamics of migration of human T cells locomoting, in real time, on gradients formed by representative. This system provides means to analyze the cytokine-induced changes in morphologies of the migrating T cells, as well as the exact patterns of their migration, random (chemokinesis) or direct (chemotaxis).

• Regulation of expression and secretion of metalloproteinases from T cells migrating through inflamed ECM
  Matrix remodeling and cell migration are dependent on degradative enzymes, including a family of enzymes termed matrix metalloproteinases (MMPs). Through their ability to degrade structural components of ECM, MMPs promote dynamic interactions between migrating cells and their environment. We are studying how the inflammatory context affects the expression of T cell MMPs. We believe that these studies will lend significant insight on the relationships between migrating cells and the milieu through which they emigrate.

 Group Members:
Dr. Liora Cahalon, Research Associate
Dr. Rami Hershkoviz, Visiting Scientist
Laura Netzer, Lab Assistant
Iris Hecht, Ph.D. Student
Asya Rolls, Ph.D. Student
Ilya Sotnikov, M.D., Ph.D. Student
Alexandra Zanin, Ph.D. Student
Michal Kardon, M.Sc. Student
Dr. Alexander Brill, Consultant
Uri Sela, M.D., Ph.D. Student
Yuri Kalashian, M.D., Visiting Scientist
Shirly Oren, M.D., Visiting Scientist

List of Publications (last 3 years)