immune system tracks pathogen invasion and cell death and responds to danger.
Defects in the immune system, such as lack of response, overreaction to
signals, or incorrect recognition of antigen as self or foreign, can cause
human diseases including cancer, autoimmunity and uncontrolled pathogen
immune system includes many different cell types that can be divided into two
groups: innate immune cells, which provide the first line of response, and
adaptive immune cells, which are activated by the innate immune system based on
the recognition of specific antigen.
cells (DCs) provide a bridge between the innate immune system and the adaptive
immune system. DCs present foreign antigens and self-antigens to T cells, and
use additional signals, by expressing cell surface receptors (for example CD86
and CD80 to activate T cells or PD-L1 to suppress T cells) and secreting
cytokines such as IL-12 or IL-10, to control the adaptive immune response.
These complex interactions between immune cells are often interrupted by
bacteria, viruses, worms and also cancer, all of which can suppress the immune
Our main goal is to investigate the
effect of immunosuppressive signals on innate immune cells, especially on
dendritic cells. We screen for new genes, that can be targeted and reverse
the effect of immunosuppressive signals, thus keeping the immune system active
even under these conditions (that exist in cancer).
this end we will further explore the effect of cancer on DC function. The tumor
microenvironment (TME) is enriched with suppressive signals that cause down
regulation of the immune system, alter the immune response to tumors and
promote cancer development.
studies have shown the importance of proper function of DCs in cancer and there
are a few examples in which targeting specific genes in DCs resulted in those
cells acquiring resistance to the TME's hazardous effects and partially
restored the immune system's ability to fight cancer. While those experiments
emphasized the importance of DCs in cancer, they also revealed the great
potential of further investigating the interaction between malignant cells and
immune cells and the potential of rational manipulation of DCs to fight cancer.
are using three approaches to elucidate the suppressive effect of cancer on
of tumor infiltrating cells to explore the dynamic effect of malignant cells on
immune cells and DCs,
applying massive single cell RNA-seq methods.
2. Searching for the genes expressed by DCs that
are essential for the transfer of the suppressive signal in DCs using genome wide CRISPR/CAS-9 screens and
advanced methods to explore genetic interactions.
3. Studying the molecular mechanisms of the genes
that we discover.
addition, we apply state of the art technologies including genome-wide CRISPR
screens and massive single cell RNA-seq experiments to explore:
1. Host-pathogen interactions.
2. Herpes viruses control of lytic
and latent infection.
3. The biology of rare diseases.