Pekka Jaako studies how normal and malignant hematopoietic formation is regulated at the level of the ribosome

What is your scientific background? 

I have a master’s degree in biology from the University of Oulu, Finland. In connection to these studies, I spent one year as an Erasmus student at Lund University where I did my degree project in the laboratory of Dr. Stefan Karlsson, and ultimately, I ended up staying there as a PhD student. My PhD work focused on studying how mutations in genes encoding ribosomal proteins impair red blood cell production in a rare disease called Diamond-Blackfan anemia. This project got me interested in this fascinating group of inherited bone marrow failure syndromes called ribosomopathies that are all caused by distinct defects in ribosome biogenesis but mysteriously manifest with highly tissue-specific phenotypes. Following my PhD studies and a short postdoctoral training in the laboratory of Dr. David Bryder, I felt that I had acquired the skillset to characterize hematopoiesis but needed to learn more about ribosomes. I therefore did another postdoctoral training in the laboratory of Dr. Alan Warren at the University of Cambridge who is one of the leading scientists in the field of ribosomopathies with a particular focus on structural aspects of ribosome biogenesis. This training helped me to gain a more comprehensive understanding on ribosomopathies, in addition to learning relevant methodology including polysome profiling that we have now set up here in Gothenburg.

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What are the big scientific questions you are working with? Is there a vision for your research group? 

The overall goal of my laboratory is to understand how normal and malignant hematopoeisis are regulated at the level of the ribosome. We recently published a proof-of-concept study for ribosome assembly as a therapeutic target in acute myeloid leukemia, and we are now pursuing this topic further in the context of clinical protein synthesis inhibitors. We have also made an exciting observation that may help to explain why the ribosomal defect in patients with Shwachman-Diamond syndrome specifically impairs the generation of a type of white blood cells called neutrophils.

Our research combines mouse models with mRNA translation and single-cell profiling techniques. We hope that this approach will provide fundamental insights into disease mechanisms that can be applied to develop mechanism-based treatments for blood diseases.

Why did you start with research?

I became interested in genetics in high school and went on to study it further in university. During this time, I worked a couple of summers as a research assistant and noticed that I really enjoyed both the intellectual challenge as well as the social aspects of doing research.

What co-operations do you have today: with other scientific group, with industry, or clinical?

We have established workflows to characterize and genetically manipulate hematopoietic stem and progenitor cells that have allowed us to contribute to the ongoing research in our environment. We have also purchased specialized equipment to quantify and fractionate ribosomes that we are sharing on a collaborative basis with many local scientists as well as those at AstraZeneca. Finally, we have had a good initial contact with local clinician scientists, and we hope that we will soon be in position to start translating our research toward the clinic.

Short description of your research for non-academics

All cells in our body need to produce proteins in order to grow and divide. This task is performed by ribosomes, which are often referred to as the protein factories of the cell. Recent research has revealed that inherited defects in ribosome function cause a group of diseases known as ribosomopathies. Shwachman-Diamond syndrome is a ribosomopathy that can result in impaired pancreatic function and a deficiency of white blood cells. My laboratory has generated a mouse model that mimics the ribosomal defect seen in patients with Shwachman-Diamond syndrome. We aim to use this model to deepen our understanding of the Shwachman-Diamond syndrome disease mechanisms and to apply this knowledge to develop new treatments for this disease. In another line of research, we have applied mouse models of a type of blood cancer called leukemia to show that leukemia cells have a relatively high protein synthesis rate and that disruption of ribosome function in these cells damages their function. Building on this finding, my laboratory is trying to develop new treatments targeting the ribosome for patients with leukemia.

November 2024

Interview by Niclas Lundh

More information can be found on  Pekka Jaako's research page 

Editor: webb@biomedicine.gu.se