Thesis supervisor: Lajos Vince Kemény
Location of studies (in Hungarian): Semmelweis Egyetem Abbreviation of location of studies: SE
Description of the research topic:
Melanoma is one of the most rapidly progressing cancers in humans. Despite decades of basic research, translational and clinical research, the 5 year overall survival of metastatic melanoma remains below 50%. Therefore, the development of novel therapeutic strategies is warranted.
In the last few years a new therapeutic approach, the immune checkpoint blockade, has revolutionized the treatment of melanoma. However, a major problem in combating the PD1 / PDL1 immune checkpoint signaling pathway in melanoma is the emergence of resistance mechanisms. Several different mechanisms of resistance have been proposed, including the dedifferentiation of melanoma cells, which promote a less differentiated, weakly immunogenic phenotype. Our unpublished preliminary results suggest that dedifferentiated melanoma cells are susceptible to ferroptosis, a recently discovered new form of cell death.
The overall goal of this PhD project is to identify vulnerabilities associated with dedifferentiation of melanoma cells, with a special focus on the promotion of ferroptosis, a novel form of non-apoptotic, immunogenic cell death.
During the project, the PhD student will perform genome-wide crispr screens in various human melanoma models in order to identify specific regulators of ferroptotic cell death. After identifying genes associated with either resistance to ferroptosis or genes sensitizing to ferroptotic cell death, the PhD student will evaluate the pathways responsible for the regulation of ferroptosis using bioinformatic tools. Based on the results of the screening, the student will validate the top targets and examine the exact function of the new targets using various biochemical and cellular assays. The relevance of identified genes for melanoma progression, survival and clinical benefit of immune checkpoint blockade is evaluated by analyzing transcriptomic and clinical data of melanoma samples obtained from patients.
During the program, students are expected to acquire and develop strong cell biological, molecular biological and bioinformatic skills, as well as presentation and communication skills. Due to the multidisciplinary nature of the project, strong collaboration skills are also expected to develop. In addition, certain aspects of the project can be carried out in cooperation with the Massachusetts General Hospital and Harvard University and Technische Universitat of Munchen.
The project can be tailored to the interests and individual goals of the prospective doctoral student upon discussion and mutual agreement.
Deadline for application: 2024-06-30
2024. IV. 17. ODT ülés Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).
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