Lung cancer is the most common cause of cancer related deaths worldwide. In Finland, it is the second most common cancer type among men and forth common among women. Typically the disease is diagnosed only at an advanced state due to the asymptomatic disease progression. The late diagnosis combined with high level of tumour heterogeneity make treating lung cancer very challenging.
Detailed information about molecular profiles of lung tumours has been generated. However, very little is still known about the functional importance of many of the detected genetic alterations. Such information is crucial for translating the molecular findings into clinic to benefit the patients.
The main aim of M.Sc. Jenni Lahtela’s thesis entitled "Studying the functional relevance of lung cancer genetic drivers in their physiological niche” was to get more clinically meaningful information on genetic and cell type-specific factors contributing to the development and progression of lung cancer. Her doctoral dissertation will be publically examined on Friday, 19 February, with the permission of the Faculty of Medicine of the University of Helsinki.
Jenni Lahtela graduated from the University of Oulu, in 2008 having genetics as her major subject. In 2009 she was offered a rotational PhD student position at FIMM and worked for a few months in the group of FIMM-EMBL Group Leader Sergey Kuznetsov. The next rotation in the group led by FIMM-EMBL Group Leader Emmy Verschuren ended up also being the last since she received a graduate school position and decided to start her thesis work in Emmy’s group.
– Funnily enough, I can say that I’ve been working at FIMM longer than my supervisor who joined the institute some months after me, said Jenni with a grin.
Jenni’s thesis consists of two publications and one manuscript currently being under review. The starting point of her thesis was to validate the functional importance of a gene called EPHA3. Mutations within this gene are commonly found in lung tumours and based on prior results the gene was suspected to act as a tumour suppressor. Using validation experiments in cell lines, she was able to show that EPHA3 has tumour supressor-like properties. However, knocking-out the gene in a mouse model did not result in increased amount of lung tumours or defects in lung development.
– Our results highlight the complexity and redundancy of biological signalling networks, which can challenge the functional validation of putative cancer genes, as in this case. Even though EPHA3 may act as a true lung tumour suppressor, a solid functional proof for this is still lacking due to compensatory mechanisms or differences between mice and humans, explained Jenni.
In the second part of the thesis work she concentrated on studying the impact of the cell-of-origin on lung cancer development by utilising genetically engineered mouse models of lung cancer. The group showed that cells in the lung airways were more prone to develop faster growing and progressing tumours compared with cells in the alveolar space. Interestingly, the results suggested that a key factor explaining the differences in the aggressiveness of the cancer was an immunosuppressive microenvironment.
– These findings support the importance of the niche specific experiments and highlight the relevance of mouse model studies when treatment options such as immunotherapies are to be developed for human lung cancer. We are currently investigating the extent to which our microenvironment findings correlate with human lung tumours, Jenni continued.
Jenni Lahtela's thesis cover art: Susanna Tuononen
– Fine-tuning the laboratory protocols to effectively analyse embryonic lung development and to induce lung tumours in mice, using trial and error, has been time consuming. My determination, and my ability to end a project when needed, have been very valuable in moving my research forward.
After the work hours, Jenni’s center of the world is her dear dog called Juice. She also enjoys dancing and was the choreographer for the famous “Swinging Wing” performance, which had its premiere a few years ago at FIMM Christmas Party.
Jenni will spend at least a couple more months at FIMM to finish her experiments. Her future plans are not yet settled but she is considering to switch the focus of her post-doctoral work to human lung cancer.
The public examination of Jenni Lahtela’s doctoral dissertation will take place on 19 February 2016 at 12:00 in Lecture hall 3 at Biomedicum Helsinki 1, Haartmaninkatu 8. Professor Anton Berns (The Netherlands Cancer Institute) will serve as the opponent and Professor Tomi Mäkelä as the custos.