Group Pekka Jaako

Research group
Active research
Project owner
The Institute of Biomedicine

Short description

Research on protein synthesis control in hematopoiesis and leukemia.

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. The chemical landscape of the human ribosome at 1.67 Å resolution. (Preprint)
    Alexandre Faille, Kyle C Dent, Simone Pellegrino, Pekka Jaako, Alan J Warren.

  2. Defective ribosome assembly impairs leukemia stem cell function in a murine model of acute myeloid leukemia. (Preprint)
    Daniel Sjövall, Sudip Ghosh, Jenny Hansson, Carolina Guibentif, Pekka Jaako.

  3. eIF6 rebinding dynamically couples ribosome maturation and translation.
    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. EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome.
    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. Induction of the 5S RNP-Mdm2-p53 ribosomal stress pathway delays the initiation but fails to eradicate established murine acute myeloid leukemia.
    Jaako P, Ugale A, Wahlestedt M, Velasco-Hernandez T, Cammenga J, Lindström MS, Bryder D. Leukemia. 2017;31:213-221.
  6. Disruption of the 5S RNP-Mdm2 interaction significantly improves the erythroid defect in a mouse model for Diamond-Blackfan anemia.
    Jaako P, Debnath S, Olsson K, Zhang Y, Flygare J, Lindström MS, Bryder D, Karlsson S. Leukemia. 2015;29:2221-2229.
  7. Gene therapy cures the anemia and lethal bone marrow failure in mouse model for RPS19-deficient Diamond-Blackfan anemia.
    Jaako P, Debnath S, Olsson K, Modlich U, Rothe M, Schambach A, Flygare J, Karlsson S. Haematologica. 2014;99:1792-1798.
  8. Dietary L-leucine improves the anemia in a mouse model for Diamond-Blackfan anemia.
    Jaako P, Debnath S, Olsson K, Bryder D, Flygare J, Karlsson S. Blood. 2012;120:2225-2228.
  9. Mice with ribosomal protein S19 deficiency develop bone marrow failure and symptoms like patients with Diamond-Blackfan anemia.
    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.

More group Pekka Jaako publications on PubMed

Pekka Jaako
Photo: Carolina Guibentif

Contact information

Pekka Jaako

E-mail: Pekka Jaako

Visiting address:
Sahlgrenska Center
for Cancer Research,
Medicinaregatan 1F
413 90 Gothenburg