Congratulations to Alexandre HALLER on the acceptance of his thesis!
His work, supervised by Irwin DAVIDSON,
is entitled: "Characterization of long noncoding RNA LENT, a potential therapeutic target in cutaneous melanoma."
Summary of his research:
Melanoma is the most aggressive type of skin cancer, representing only 1% of skin cancers but causing the majority of deaths related to these cancers. Metastatic melanomas are treated with immunotherapy or targeted MAPK inhibition. However, primary or acquired resistance pushes researchers to explore new therapies. In this context, the host lab identified a series of long noncoding RNAs (LncRNA) specific to melanoma.
The project focuses on the LncRNA LENT (LncRNA Enhancer of Translation), which is highly expressed in melanomas compared to other cancers or tissues. LENT is regulated by the transcription factor MITF and is expressed in melanocytic melanoma cells. Silencing LENT inhibits melanoma proliferation and induces apoptosis. Purification of LENT coupled with mass spectrometry revealed a selective interaction with the G quadruplex resolvase DHX36, which regulates mRNA translation and localizes to mitochondria in melanoma cells. Deleting LENT modulates the association of many mRNAs with DHX36 and polysomes, impacting their translation. This deletion promotes mitophagy and reduces the stress response capacity of melanoma cells, leading to cell death. Thus, LENT represents a novel therapeutic target for treating cutaneous melanoma.
Skills acquired at IGBMC:
During his years of research, Alexandre Haller developed numerous skills, both scientific and transversal. He deepened his knowledge of his research field and mastered several biochemical techniques, as well as bioinformatics skills. He also gained experience in task management, organization, and student supervision. His involvement in the CSE and the lab council helped him better understand the internal workings of a research lab and, more broadly, of an enterprise.
Life at IGBMC:
What he particularly appreciated at IGBMC was the stimulating work environment and his team's good integration. He valued the regular exchanges with platforms and other researchers, finding these discussions inspiring. Lastly, he met many amazing people who made him happy to come to the institute every morning.
Collaborations:
During his thesis, Alexandre Haller closely collaborated with Eric Ennifar’s team at IBMC to understand LENT's structure, carrying out key experiments included in his thesis. He also worked with Professor Thomas Baumert’s Hepsys team, and they recently co-published an article on the circadian rhythm’s impact on HCV* infection. Finally, he collaborated with Alexandre Detappe’s team at ICANS on designing polymers to deliver therapeutic molecules targeting LENT and potentially other LncRNAs.
Funding and partners:
His funding began with a three-year PhD scholarship won through the IMCbio competition, followed by a fourth-year grant from the Fondation pour la Recherche Médicale. His team, supported by the Ligue contre le cancer, also received significant financial backing from SATT Connectus for this project.
Future projects
Alexandre Haller is starting a program at the Faculty of Economic and Social Sciences of Strasbourg. He will be pursuing the IPI (Innovative Project Engineering) master’s degree, which includes four months of courses in management, business administration, and entrepreneurship, followed by a six-month contract with companies. This training is designed for PhDs who aim to transition into the private sector after their thesis.
Publication link:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362569/