Research

Our lab investigates the interactions between macrophages and other cells, in the context of the inflammatory microenvironment. Macrophages are regulatory cells that can function in a wide range of activities, ranging from killing bacteria and tumor cells to healing wounds and promoting angiogenesis. This enormous plasticity requires that the macrophage will be able to sense its changing microenvironment and react to it in different ways. Thus, unlike lymphocytes that are committed to only one way of activation, the same macrophage can act in many different ways.

EMMPRIN mediates macrophage (red) and tumor cell (green) interactions

EMMPRIN mediates macrophage (red) and tumor cell (green) interactions

EMMPRIN/CD147 as a regulator of macrophage interactions:

Tumor cells take advantage of this ability, and actively recruit macrophages into the tumor mass, only to reprogram them to secrete pro-angiogenic and pro-metastatic factors that are necessary for tumor growth and metastasis (e.g. VEGF and MMPs). One of the proteins that mediates this interaction is EMMPRIN/CD147, which is overexpressed on many types of tumor cells, and induces macrophages to secrete high amounts of VEGF and MMPs, to promote angiogenesis and metastasis. EMMPRIN  expression is also elevated in inflammatory epithelial cells and plays a role in angiogenesis in autoimmune diseases.

We currently explore:

  1. Cancer Immunotherapy: targeting EMMPRIN by either specific antibodies or by active vaccination.
  2. The neuronal and spatial regulation of EMMPRIN expression.
  3. Signal transduction pathways regulating EMMPRIN activity.
  4. EMMPRIN as regulator of angiogenesis  in autoimmune diseases.

Post-transcriptional control of tumor-macrophage interactions by microRNA:

Macrophage plasticity means that the same cell can mediate either tumor cell death (for example, by secreting cytotoxic mediators such as nitric oxide or TNFα),  or survival (for example, by secreting pro-angiogenic molecules such as VEGF, or immunosuppressive mediators that help the tumor evade recognition by the immune system, such as TGFβ). We speculate that microRNAs (miRNAs) take part in the regulation of this plasticity, and focus on two such mechanisms (nitric oxide which is pro-apoptotic, and EMMPRIN which is pro-angiogenic). We ask if miRNAs, and more specifically miR-146a, may function as a regulatory switch for life and death decisions.

We currently explore:

  1. The function of miR-146a as a regulatory switch between tumor cell death and angiogenesis: implications for therapy.
  2. microRNA as biomarkers of Rheumatoid Arthritis

Evaluating the dynamic inflammatory status of patients:

Inflammation is dynamic, and while it often starts as a pro-inflammatory process that is designed to kill invading pathogens or tumor cells, it should end as an anti-inflammatory process that heals the wound and tissue damage.  In clinical conditions such as sepsis, the difference between SIRS (systemic inflammatory response syndrome, a pro-inflammatory response) and CARS (compensatory anti-inflammatory response syndrome) may mean that different treatments to the patient may be required. However, we still do not have enough reliable biomarkers to assess the inflammatory status of the patient in each time point.

We currently explore:

  1. Pro-angiogenic markers in Rheumatoid Arthritis (RA) and Psoriatic arthritis (PsA).
  2. Macrophage phenotyping in RA and cancer.