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Researchers
  • Dr.  Oren Parnas
Dr. Oren Parnas
 
About the Lab

 

The 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 infection.

 

The 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.

 

Dendritic 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 response.

 

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).

 

Toward 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.

 

Several 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.

 

We are using three approaches to elucidate the suppressive effect of cancer on DCs:

1.   Profiling 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.

 

 

In 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. ​

Open Positions
 Excellent, high motivated students and post-docs are welcome to apply.

Please send your CV to orenp@ekmd.huji.ac.il
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