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H2020Individual fellowship2018–2020

KILNEV · Killing Senescent Cells as a Novel Method to Eliminate Nevi

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2018-04-01 → 2020-03-31
EU contribution
€165,599
Participants
1
Scheme
MSCA-IF-EF-ST

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Results in brief

Killing Senescent Cells as a Novel Method to Eliminate Nevi

The current project entails the elucidation and evaluation of novel genes which senescent nevus cells (pigmented moles) utilise to maintain survival. Nevus cells arise when skin cells called melanocytes enter a state of gorwth arrest termed 'senescence'. Nevus cells can eventually develop into malignant melanoma, a highly aggressive skin cancer. Therefore targeting cell death in nevus cells may act as a novel preventative measure against melanoma development. This is especially important considering rates of melanoma are increasing in most European countries and current therapies against melanoma such as chemotherapy and immunotherapy are highly invasive, expensive and can result in toxic side effects. The objectives are: 1) Elucidate and validate new genes of interest which modulate survival in senescent melanocytes. 2) Investigate whether siRNA mediated knockdown of these genes induce death of nevus cells in mice.

Data: CORDIS, © European Union

Project objective

Melanoma is the most aggressive type of skin cancer, and its spread to distal tissues is often a death sentence. Immunotherapies have led to increased survival rates but they are extremely expensive and efficient for approximately only 25% of patients. Therefore research into new methods to prevent or arrest the progression of melanoma is urgently needed. Nevi are pigmented lesions on skin which consist of a clonal mass of melanocytes in a state of proliferative arrest termed ‘senescent’. This state prevents further hyperplasia, but if mutations occur in proteins required to maintain senescence, cells can re-proliferate and progress into melanoma. Selectively clearing senescent melanocytes may therefore be an effective strategy to improve current preventative measures against melanoma. This project will use a combination of interdisciplinary techniques to identify and target molecular components that confer survival to senescent melanocytes. First, I will use whole-transcriptome analysis to identify novel genes associated to cell survival. Second, genes of interest will be validated via siRNA mediated gene silencing in vitro using techniques in molecular biology to assess viability and apoptosis. Third, selected targets will be validated in vivo using a unique novel mouse model established in the host laboratory where nevi can be induced and senescent cells can be quantified by luminescence. Successful identification of these targets may lead to future development of new therapies which help reduce the health and economic impacts of malignant melanoma.

Original text from CORDIS.

Participants

  • ACADEMISCH ZIEKENHUIS GRONINGEN · GroningenCoordinatorNetherlands

Links

Data: CORDIS, © European Union