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Research Interests

I am a principle investigator in the Gene Therapy Institute since 2000. I also serve as a professor at the Hebrew University where I teach in the medical school.
In previous years our studies focused on the regulation of immune responses especially on the regulation of T cell activation during pregnancy. To better understand the full scope of immunity and how immune response plays a role in maintaining homeostasis, we shifted our focus toward macrophages that are the "first line of defense" in the various tissues, and we now study the way it is regulated by and responds to environmental cues.
We suggest that the immune system and specifically macrophages senses the broad spectrum of cellular conditions that accordingly induce broad range of responses that are aimed at maintaining homeostasis. For that end, we studied several specific cases that the relationship between microenvironment and immune cell phenotype and response:
Healthy cells avert immune recognition and maintain tolerance
The interaction of antigen presenting cells (APC) and T cells is pivotal for a productive immune response. APC are at the center of a critical decision point leading to immune activation versus immune tolerance. In a series of studies we have established a novel mechanism for APC tolerazation that is based on cell:cell interaction and induce T cell unresponsiveness.
Macrophages promote cellular adaptation to stress
In contrast we have demonstrated that macrophages respond to signals emanating from cells suffering from oxidative stress and enhance DDR and facilitate DNA break rejoining via HB-EGF release
As a consequence of these studies we suggest a broader view of the immune system as a “quality control” system whereby macrophages secrete or express “restorative signals” that help cells exposed to stressful conditions recover and hence help maintaining homeostasis.
Current studies focus on:
  • A role for macrophage-assisted DNA damage repair in carcinogenesis.
  • A role for macrophage-assisted DNA damage repair in tumor acquisition of chemo- and radiotherapy resistance.
  • Do age-related modulation in innate immunity may account for the decline in DNA damage resolution and the accumulation of DNA breaks with age?
Figure 1: EGF-receptor ligands accelerate DNA damage repair
Our team is interested in the way macrophages through the release EGF ligands regulate DNA damage response in neighboring cells and accelerates DNA damage resolution. The generation of double strand breaks and their resolution is monitored by the appearance of γH2AX foci (green) that are co-localized with 53BP1 (red) in the nucleus (blue).
Figure 2: A suggested model for macrophage-derived cell non-autonomous DNA damage response and repair
Genotoxic insult to a tissue results in DNA damage that activates the DDR. Macrophages are recruited to the damaged tissue and release HB-EGF that triggers the EGFR signaling pathway, which in turn enhance DDR and accelerates DNA damage resolution.