Research

Our lab investigates the interactions between macrophages and other cell types. 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, and their plasticity is determined by the changing microenvironment and signals emitted from the tissue cells.

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 actively recruit macrophages into the tumor mass, and reprogram them to secrete pro-angiogenic and pro-metastatic factors that are necessary for tumor growth and metastasis (e.g., VEGF and MMPs). EMMPRIN/CD147 is gaining recognition as a protein that mediates these interactions, which is overexpressed on many types of tumor cells, and induces macrophages to secrete high amounts of VEGF and MMPs that promote angiogenesis and metastasis. EMMPRIN  expression is also elevated in inflammatory epithelial cells and plays a role in angiogenesis in autoimmune diseases, such as Rheumatoid Arthritis (RA), Psoriatic arthritis (PsA) and type 2 Diabetes Mellitus (T2DM).

We currently explore:

  1. Cancer Immunotherapy: targeting a novel epitope in the EMMPRIN protein by either a monoclonal antibody or by active peptide vaccination.
  2. Signaling pathways that regulate EMMPRIN expression and activity.
  3. EMMPRIN as regulator of angiogenesis in autoimmune diseases (RA, PsA, T2DM).

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

Macrophage plasticity means that the same cell can mediate either tumor cell death (by secreting cytotoxic mediators such as nitric oxide or TNFα), or survival (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 investigate how miR-146a and other miRNAs regulate processes such as survival (e.g., angiogenesis) 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. MicroRNAs as biomarkers of Rheumatoid Arthritis and Psoriatic Arthritis

Evaluating the dynamic inflammatory status of patients:

Angiogenesis is necessary in inflammation, and ensures the constant supply of nutrients and oxygen to the immune infiltrate. However, pathological angiogenesis could be involved in clinical complications (e.g., retinopathy, nephropathy). We still do not have sufficient reliable biomarkers to assess the inflammatory/angiogenic status of a patient in any given time point.

We currently explore:

  1. Pro-angiogenic markers in Rheumatoid Arthritis (RA) and Psoriatic arthritis (PsA), and in particular EMMPRIN.
  2. Effects of disease-modifying anti-rheumatic drugs (DMARDs) on pro-angiogenic factors and miRNAs in RA and PsA.
  3. Effects of insulin and glucose on endothelial cell expression of EMMPRIN and on angiogenesis in T2DM patients