Outline The significance of pigmentation in melanoma biology and treatment [supervisors: dr hab. Anna Brożyna, prof. UMK, NCU/prof. Andrzej T. Slominski, University of Alabama at Birmingham, USA]

Malignant melanoma is the most rapidly increasing malignancy in the white population and its mortality rate is surpassed only by lung cancer. Unfortunately, since many years there has been no significant progress in efficiency of advanced melanoma therapies and survival rate of patients with metastatic melanomas. Surgical excision is an effective treatment only for cure of an early stage melanomas. Melanoma is a type of skin cancer that arises from melanocytes, the cells producing melanin, present predominantly in the skin. Its major role is protection against the harmful actions of solar radiation. It has been well accepted that melanin could act as protector against skin cancers and melanoma. However, under pathological conditions (e.g., melanoma), melanogenesis can induce genotoxic and mutagenic effects via toxic intermediates of the pathway, thus contributing to tumor progression. Melanin precursors and intermediates can facilitate melanoma progression and further development of the disease. The antioxidative properties of melanin, under physiological conditions protects skin against environmental insults, but under pathological conditions can attenuate radio- photo- and chemotherapy, with net undesirable clinical effect. The results of our previous research showed significant differences in biology and behavior of amelanotic and pigmented melanomas, both in in vitro experiments and in clinical samples. We found that melanogenesis shortens overall survival and disease-free survival in patients with metastatic melanoma. Patients with pigmented melanomas treated with radiotherapy showed significantly shorter survival when compared to amelanotic once. In melanoma microenvironment melanin was related with lower number of intratumoral and peritumoral lymphocytes in primary lesions indicating, that melanin demonstrates powerful immunosuppressive properties. In addition amelanotic but not pigmented melanoma cells were sensitive to chemotherapeutic action of several drugs and natural compounds and ionizing radiation, suggesting that inhibition of melanogenesis could sensitized melanoma cells to radio and chemotherapy and could be useful method of augmenting efficiency of radiotherapy or chemotherapy in metastatic melanoma.

The aim of this study is analyzing:

-the cytoskeleton of melanoma cells in relation to pigmentation

-the effects of melanoma pigmentation, its regulation on adhesion and migration

-WNT/β-Catenin pathways in melanoma in relation to pigmentation

- WNT/β-Catenin pathways modulation by natural compounds, as melatonin or vitamin D

-effects of natural compounds, as melatonin or vitamin D on adhesion, cytoskeleton and migration of melanoma cells.

-adhesion, cytoskeleton, migration of melanoma cells and WNT/β-Catenin pathways after melanogenesis inhibition.

The abovemantioned aims should allow to identify the molecular pathways and/or processes chracterized by therapeutic potential.

What is funded

A doctoral student who does not hold a degree of doctor shall receive a doctoral scholarship.

The amount of a monthly doctoral scholarship shall be at least:1) 37% of a professor’s salary – up to the month in which the mid-term evaluation was conducted*; 2) 57% of a professor’s salary – after the month in which the mid-term evaluation was conducted*.

[*According to the legal status in 2020, the scholarship is gross: 1) 2.371,70 PLN, 2) 3.653,70 PLN.]

Duration

4 years.

Eligibility

A Master degree (a magister or a magister inżynier degree) or an equivalent degree, or the diploma, entitling to apply for the award of a degree of doctor in the country in the education system of which the higher education institution which issued it operates.

Taking part in the recruitment process.