Pluripotent stem cells for modelling thyroid cancers

Supervisor: Dr. Sabine Costagliola

Thyroid cancers are the most common endocrine malignancies. Papillary thyroid carcinomas (PTC) account for 80% of thyroid cancers with an incidence of 8/6000 (incidence increasing each year). It is therefore not a rare cancer. The most common genetic abnormality associated with PTC is the V600E mutation of the proto-oncogene BRAF. The identification of the molecular mechanisms that contribute to the initiation and/or progression of this cancer would have major implications for human health. In the absence of a tractable genetic model, our knowledge of these mechanisms remains very limited. Our lab has established an in vitro model of thyroid differentiation from pluripotent stem cells.  Fur cancer drugs screening, this organoids technology could fill the gap between conventional cell line culture and in vivo models. The objective of this project is to generate in vitro BRAF-V600E PTC organoids.

From cells genetically modified to express BRAF-V600E in a conditional manner,

  1. The candidate will explore the processes of neoplasia and organoids dedifferentiation by studying the modulations of genes expression which could be further targeted by genome edition,
  2. Drugs will be tested for their ability to induce a re-expression of thyroid markers and thus be able to offer new therapeutic perspectives.

For this, the PhD candidate will learn genomics, next-generation RNA-sequencing, immunohistochemistry, stem cell/organoids biology and cell imaging, drug screening.

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