DEPARTMENT OF ANIMAL PHYSIOLOGY

Ultraviolet (UV) from sunlight is the main trigger factor of skin cancer. By inducing mutations in tumor suppressor genes, UV light induces neoplastic (cancerous) cell growth. This is more likely to occur in keratinocytes, the principal epidermal cell type, than in cutaneous melanocytes, which would eventually give rise to malignant melanoma. Mutations can either affect intrafollicular epidermal keratinocytes or those residing in hair follicles, leading to either squamous cell carcinoma (SCC) or basal cell carcinoma (BCC). These non-melanocytic forms of skin cancer and its precursors (non-melanoma skin cancer, NMSC), imposes a significant burden on public health and health related quality of life. Our research focusses on the pathobiology of squamous cell carcinoma of the skin and its main precursor lesion, actinic keratosis. In cooperation with medical centers and biotech industry, we employ in vitro models and human tissue samples to investigate tumor cell behavior, mechanisms of tumor formation and differential gene expression. One of our key interests is the involvement of cancer stem cells in the abovementioned processes. Our investigations rely on methods as cell and tissue culture, (immuno)histology, fluorescence microscopy, molecular biology and functional cell biological assays (cell death, proliferation, migration, invasion). In addition, we test up-to-date pharmacological interventions in our models, particularly photodynamic therapy (PDT). In this therapeutic approach to skin cancer therapy, a photosensitizer is applied to the tumor, which enriches to a much higher extend in neoplastic than in healthy cells. Subsequent exposition to light of an appropriate wave length induces the intracellular formation of reactive oxygen. This induces oxidative damage to mitochondria and eventually cell death of the neoplastic cells. We analyze the effects of PDT to tumor cells using microscopy as well as fluorimetric and biochemical assays. We especially strive to describe mechanisms which relate PDT efficacy as well as cellular PDT-resistance in both cancer cells in general as well as in cancer stem cells.

contact person: Dr. Ben Novak