Researcher of the Month

November 2023

After K. Albin Johansson Cancer Research Fellow Anna Vähärautio did her PhD on how one gene is regulated by one transcription factor, she wanted to broaden her horizons to genome-wide scale. For this she joined the laboratory of Jussi Taipale and ended up in Karolinska Institutet, Sweden. In Sweden she did not learn too much Swedish but still a useful language: programming language called R. In addition to R, Anna utilized other computational data analysis tools to make sense of the large data sets typically obtained from genome-wide analyses. In Karolinska, Anna also developed the first laboratory method that used unique molecular identifiers (UMIs) in RNA-sequencing, a methodology that is currently of key importance when analyzing the miniscule amounts of RNA found in individual cells.

From basic research to translational ovarian cancer research

After years spent in basic research, Anna shifted to a more translational context. She applied her knowledge of wet-lab method development and bioinformatics to study how ovarian cancer becomes resistant to chemotherapy by using single-cell RNA sequencing. The method was at that time just being developed and it allowed to measure expression of all genes in individual tumor cells which was not possible before. The method utilizes UMIs that Anna and her colleagues developed earlier, so she had some understanding of what it means to deal with tiny amounts of RNA.  

What does not kill you makes you stronger?

Across all cancers, resistance to chemotherapy arises since tumor cells are not identical and thus also respond differently to the treatment. Single-cell RNA sequencing is especially suited to study this heterogeneity within the tumors, to reveal which features and in best case even mechanisms allow some of the tumor cells to survive through the treatments. 

Ovarian cancer has a poor prognosis: less than half of high-grade serous ovarian cancer (HGSOC) patients survive more than five years from diagnosis. Typically, the tumors respond first well to chemotherapy, but become resistant after repeated treatments, allowing the cancer to regrow, finally killing the patient. Currently, Anna’s research group studies ovarian cancer drug resistance from many different perspectives. The group is especially interested, how the tumor cells, that will later survive the treatment, are “prepared” or primed to become resistant. In a previous study, Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer, Anna’s lab and collaborators discovered of a stressed cellular state that is associated with both pre-existing and induced chemotherapy resistance in ovarian cancer. 

Now, the lab aims to reveal whether - and how - previous stress encounters play a role in pre-existing resistance and putative adaptation during the treatment. To address this, Anna just received an ERC Consolidator grant for her project What doesn’t kill you: overcoming primed and adaptive mechanisms of treatment resistance in ovarian cancer (STRONGER). Within the project, Anna’s group will develop methodology to time travel across the period where treatment resistance develops, by combining their sister cell lineage tracing approach ReSisTrace to stress recording in individual cancer cells. By the histories of individual cancer cells, they aim to reveal how previous adaptations to stressors shape the adaptation and fate of individual cancer cells during anti-cancer treatment. This information will then be used to change the fate of resistant cancer cells by correctly timed co-treatments. The final aim of the project is thus to identify effective and personalized sequential treatment strategies for patients with poor response ovarian cancer.

Moreover, the group tries to reveal how the genetic aberrations in the tumor cells, the surrounding non-tumor cells affect the cellular state and treatment. The group also studies how normal gene programs are maintained as distorted versions in tumors and how this affects resistance. Anna thinks it is important to keep a multi-perspective view to avoid ending up being characters in the story of blind men and the elephant. According to Anna, it is of vital importance to get a more complete picture of the complex treatment resistance in cancer, and this requires both multidisciplinary team and interdisciplinary collaborations.

Family, tennis, and social activities counterweight work

Like most people Anna’s age, she tries to balance between work and family with 8- and 10-year-old girls, meaning that there are constantly many balls in the air. As a countermeasure, Anna started learning tennis a couple of years ago. She really enjoys it even though it is very difficult for her middle-aged brain but exactly because of that, requires her full attention. Anna also enjoys running all year around, reading as well visiting museums and doing all kinds of social activities with her family and friends.