Researcher of the Month

April 2023

FICAN Research Professor Juha Klefström graduated in genetics from the University of Helsinki and is a molecular biologist by training. He received his PhD in 1997 in the field of molecular cancer biology, also from University of Helsinki. Since his PhD, he has been working as a full-time scientist in the field of cancer biology. Juha did his 2-year postdoctoral training in Imperial Cancer Research Fund/Cancer Research UK in London and spent the next three years in the University of California, San Francisco (UCSF). After his postdoctoral period, he returned to Finland and started his own laboratory with affiliation in Research Programs Unit, University of Helsinki, where he is still working. 

Discovery: MYC cancer protein makes cells extremely vulnerable to programmed cell death

The long-term focus of Juha’s laboratory is to identify specific vulnerabilities in cancer cells caused by high expression level of MYC cancer protein. Juha discovered this interesting concept that high levels of MYC make cells extremely vulnerable to programmed cell death pathways already when he was doing his PhD. He added on a whim a soluble protein called tumor necrosis factor (TNF) to fibroblast cells that either had MYC turned off or on. TNF killed only those cells that had MYC turned on. Although it was soon found that TNF cannot be used as a cancer medicine to treat patients, Juha figured that there are many other biological cell pathways that kill efficiently those cells with high levels of MYC but leave healthy cells unharmed. These pathways can be activated with anticancer drugs and such pathways are called therapeutically actionable. Since MYC is highly expressed in more than 70% of cancer cells, Juha believes that finding drugs that strike very specifically cancer cells with high MYC expression could be revolutionary for the goal of developing efficacious but at the same time safe cancer therapies. 

Developing a new research platform with the help of breast cancer patients

According to Juha, MYC is difficult to study in cultured cancer cell lines because it is expressed at high levels all the time. Therefore, Juha’s research group has established tumor tissue models for the laboratory experiments using live fragments of breast cancer tissue donated by Finnish breast cancer patients. This PDEC platform has been highly successful, and it has enabled Juha and his team to study aspects of MYC biology that no one has been able to study before. Thanks to PDECs and the Finnish patients who donated the samples, during the past years Juha and his team have been able to expand their MYC studies to certain aggressive subtypes of estrogen receptor positive (ER+) breast cancer. For these studies, they first established a PDEC model for ER+ breast cancer since no such models were available for research before. This part of the research was published in the journal Nature Communications with a title Compressive stress-mediated p38 activation required for ERα + phenotype in breast cancer. 

Back to roots: a collaboration with the UCSF

Recently, Juha and his team received a large grant from the United States, which allowed them to start a tight collaboration with the UCSF with a group that has special skills, knowledge and clinical perspective to therapeutic strategies that combine MYC-directed therapeutics with immunotherapies. Juha has spent most of his time at the UCSF this year to coordinate this collaboration. Their first joint paper, Combinatorial immunotherapies overcome MYC-driven immune evasion in triple negative breast cancer, was just published in Nature Communications. The study shows, how immunotherapies can overcome the suppressive effects of MYC on anti-tumor immunity. Juha and his team are continuing this research line so there will be interesting results and publications coming soon.

Playing electric quitar and ice swimming in the Pacific Ocean

Apart from MYC and other work and when being in Helsinki, Juha plays electric guitar in an academic rock band called Underdocs. In San Francisco he has practiced mindfulness by swimming regularly in the Pacific Ocean, an experience equivalent to ice swimming in Finland.