Who is Christian Stehlik?

The focus of our lab is to understand the molecular mechanism of inflammation and how chronic inflammation is linked to cancer.  A main interest is the production of the pro-inflammatory mediator interleukin-1 beta (IL-1b).  This protein, which initiates and perpetuates inflammatory reactions, is primarily produced by macrophages, which are a specific type of white blood cell.  Normally, IL-1b is important to promote acute, self-limiting inflammatory reactions to eliminate infections and to promote wound healing.  However, chronic and excessive production of IL-1b contributes to human diseases, including cancer.

True malignancy begins, once tumor cells begin to invade surrounding tissue and eventually break from the primary tumor to establish metastases at secondary sites.  Macrophages are actively recruited by cancer cells into the tumor microenvironment.  Although, macrophages are capable to kill tumor cells, they become frequently manipulated by cancer cells to support tumor growth by providing the needed cytokines, proteases and growth factors for cancer cells to become malignant, and are referred to as tumor-associated macrophages.  More than 15% of all cancers are known to arise from chronic inflammation, including breast, cervical and ovarian cancer. Thus, there is focus on blocking macrophages and inflammation as cancer treatment.  IL-1b from macrophages is required for the invasiveness of tumor cells and metastasis and high IL-1b levels within tumors are associated with more aggressive tumors and bad prognosis, and include breast, colon, lung, head and neck cancer and melanoma.  Anti-IL-1b therapy is investigated for cancer patients.

We study the molecular mechanism by which macrophages produce IL-1b and how one can block chronic and excessive IL-1b production.  We identified 3 novel proteins in human macrophages that can inhibit IL-1b generation and are currently investigating their role in breast cancer metastasis.  In particular we are studying their contribution to the generation of IL-1b in macrophages, their contribution to the recruitment of macrophages to primary tumor sites/cancer cells and cancer cell metastasis.