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Research summary

Ribosomes are the conserved molecular machines responsible for protein synthesis in all cells. Despite this ubiquitous function, inherited mutations in genes encoding components of the ribosome machinery cause a class of human disorders (ribosomopathies) that manifest with tissue-specific phenotypes and associate with an increased risk of cancer.

In particular, most ribosomopathies lead to bone marrow failure and increased predisposition to myelodysplastic syndrome and acute myeloid leukemia. More recently, acquired mutations in ribosomal protein genes have also been discovered in sporadic hematological and solid malignancies.

Our research seeks to understand the role of protein synthesis control in normal and malignant hematopoiesis. Our ultimate goal is to apply these findings to develop therapies for ribosomopathies and leukemia. 

Research tools and resources

We have established novel mouse and cellular model systems to study the consequences of specific defects in ribosome function on the hematopoietic system and leukemia. We use a range of cellular and molecular biology methods, including advanced flow cytometry, qPCR, WB, RNAi and CRISPR/Cas9-based approaches. 

Current group members

Pekka Jaako, PhD, Principal investigator (Junior PI)
Anna Hogmalm, PhD
Daniel Sjövall, PhD Student

Selected publications

1. 
   Daniel Sjövall, Sudip Ghosh, Narcis Fernandez-Fuentes, Talia Velasco-Hernandez, Anna Hogmalm, Pablo Menendez, Jenny Hansson, Carolina Guibentif, Pekka Jaako. Cell Rep. 2024 Oct 15;43(11):114864.
    

2. (Preprint)
   Alexandre Faille, Kyle C Dent, Simone Pellegrino, Pekka Jaako, Alan J Warren.
    

3. 
   Jaako P, Faille A, Tan S, Wong CC, Escudero-Urquijo N, Castro-Hartmann P, Wright P, Hilcenko C, Adams DJ, Warren AJ. Nat Commun. 2022 Mar 23;13(1):1562.
    

4. 
   Tan S, Kermasson L, Hoslin A, Jaako P, Faille A, Acevedo-Arozena A, Lengline E, Ranta D, Poirée M, Fenneteau O, Ducou le Pointe H, Fumagalli S, Beaupain B, Nitschké P, Bôle-Feysot C, de Villartay JP, Bellanné-Chantelot C, Donadieu J, Kannengiesser C, Warren AJ, Revy P. Blood. 2019;134:277-290.
    
5. 
   Jaako P, Ugale A, Wahlestedt M, Velasco-Hernandez T, Cammenga J, Lindström MS, Bryder D. Leukemia. 2017;31:213-221.
    
6. 
   Jaako P, Debnath S, Olsson K, Zhang Y, Flygare J, Lindström MS, Bryder D, Karlsson S. Leukemia. 2015;29:2221-2229.
    
7. 
   Jaako P, Debnath S, Olsson K, Modlich U, Rothe M, Schambach A, Flygare J, Karlsson S. Haematologica. 2014;99:1792-1798.
    
8. 
   Jaako P, Debnath S, Olsson K, Bryder D, Flygare J, Karlsson S. Blood. 2012;120:2225-2228.
    
9. 
   Jaako P, Flygare J, Olsson K, Quere R, Ehinger M, Henson A, Ellis S, Schambach A, Baum C, Richter J, Larsson J, Bryder D, Karlsson S. Blood. 2011;118:6087-6096.