Dissertation defence (Medical Biochemistry and Genetics): MSc Katri Vaparanta

MSc Katri Vaparanta defends the dissertation in Medical Biochemistry and Genetics titled “Mechanisms of receptor tyrosine kinase signaling diversity: a focus in cardiac growth” at the University of Turku on 15 December 2023 at 12.00 (University of Turku, BioCity, Presidentti auditorium, Turku).

Opponent: MD, PhD Tuomas Tammela (Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, USA)
Custos: Professor Klaus Elenius (University of Turku)

Doctoral Dissertation at UTUPub: https://urn.fi/URN:ISBN:978-951-29-9551-6


Summary of the Doctoral Dissertation:

Cells receive signals from outside and inside and transmit them to acquire information about their status and to perform tasks in a process called cell signaling. Cell signaling determines all functions of the cell and therefore all functions of all organs. Most drug-based therapies function by altering cell signaling since cell signaling is disturbed in disease. Receptor tyrosine kinases (RTKs) are cell signaling molecules that reside on the cell surface and transmit signals from outside the cell to inside the cell. RTKs have been successfully targeted as a therapy for cancer, but also regulate the development and function of important organs. The structure of these molecules determines what signals they transmit. In my thesis work, I uncovered a new region in the RTKs that determines what signals they send out inside the cell. This region may in the future serve as a new way to target RTKs as a therapy for disease.

The heart requires growth signals to develop and maintain its muscle. Stress such as overload due to high blood pressure can cause the heart muscle to grow abnormally. This abnormal growth can reduce the volume of blood the heart can pump and finally lead to heart failure. Knowledge about the underlying cell signaling that leads to abnormal heart muscle growth could be used to design therapies to reduce abnormal heart muscle growth. Knowledge about the growth signals of the heart muscle can also be potentially used to renew the heart muscle after injury. In my thesis, I found new heart muscle growth signaling pathways involving the RTK ErbB4 and the cell signaling molecules STAT5b and VEGFB. Knowledge about these growth signaling pathways may facilitate therapy development for heart diseases especially since a cell signaling molecule that transmits its signals through the RTK ErbB4 has successfully alleviated heart muscle injury in clinical trials.

Omics technologies have allowed researchers to acquire extensive information about the number and state of cell signaling molecules in the cell. Computational methods are needed to model this vast amount of information into cell signaling pathways. In my thesis, I developed a computational method that can model the information acquired from omics technologies into cell signaling pathways without the use of previous knowledge. This computational method can be used to uncover new cell signaling connections that are disturbed in diseases and that can serve as new targets for drug development.
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