Petter Woll group - Leukemic stem cells

The group studies cellular and molecular mechanisms promoting establishment and propagation of leukemic stem cells. We wish to understand the cellular and molecular targets for highly recurrent mutations in hematologic malignancies, in order to prevent leukemia and treat the patient.

A group of people in front of Aula Medica in Solna.
The Petter Woll research group outside Aula Medica. Photo: Stefan Zimmerman

About our research

The major focus of our research program is towards the development and characterization of clinically relevant genetic mouse models to understand the cellular and molecular targets for recurrent leukemic mutations, and how these promote leukemic stem cell clonal advantage. To complement studies in mice, we have access to state-of-the-art patient material (viably frozen bone marrow and peripheral blood) that allows isolation and characterization of distinct hematopoietic stem and progenitor compartments. In addition, the immunological targeting of leukemic propagating cells is explored.

Because of their short half-life, millions of mature blood cells of multiple lineages are continuously replenished from a rare population of uncommitted hematopoietic stem cells (HSCs) which possess the unique ability to self-renew and to develop towards all blood cell lineages. Understanding the precise mechanisms involved in the regulation of this process is of considerable relevance for human health and disease, as these regulatory stages frequently are hijacked in hematologic malignancies.

Advances in next-generation sequencing has revealed highly recurrent mutations in hematologic malignancies. However, at what cellular stage and the molecular impact of these mutations promoting leukemic stem cell expansion, as well as perturbed hematopoietic differentiation, remains poorly understood.

Group leader

Petter Woll

Researcher
H7 Department of Medicine, Huddinge

Petter Woll started as Assistant Professor at Karolinska Institutet in 2015. His lab located at the Center for Hematology and Regenerative Medicine is focused on unravelling cellular and molecular mechanisms underlying malignant hematopoiesis.

Petter Woll received his PhD degree from the University of Minnesota in 2008, after working in the lab of Dan Kaufman focused on modelling human blood development from embryonic stem cells. He continued to study cancer stem cells in patient with myelodysplastic syndromes during his postdoc at the University of Oxford in Sten Eirik Jacobsen’s lab.

In his spare time, Petter enjoys sports, including cycling, squash and skiing, and going to concerts. His all-time top 5 favourite artists are (in no particular order): Bruce Springsteen, Radiohead, Åge Aleksandersen, The National and Nick Cave.

Group members

Stina Virding

Affiliated to research
H7 Department of Medicine, Huddinge

Stina Virding's PhD project is focused on unravelling at the single cell level the molecular dysregulation underlying leukemic stem cell clonal dominance, clonal evolution and resistance to therapy using a method that combines high-sensitivity mutation detection with whole-transcriptome analysis.

Stina received her master degree in Biomedicine at Karolinska Institutet in 2015. Before starting her PhD, she worked at King’s College, London, where she generated and characterized T-induced pluripotent stem cells from ß-cell antigen-specific regulatory T cells.

Stina loves to travel and to study abroad. During the last years she has been studying at University of Technology Sydney (Australia), XLRI Jamshedpur School of business and Human Resources (India), Leiden University (The Netherlands), Princeton University (USA) and King’s College (England).

When she is not busy in the lab, Stina enjoys skiing, sailing, dancing and playing tennis. She listens to all kind of music, some of her favourite bands include The Nationals, Bon Iver, First Aid Kit & Bo Kaspers Orkester.

Madeleine Lehander

PhD student
H7 Department of Medicine, Huddinge

Madeleine Lehander, or Madde as she is usually being called, received her master degree in Biomedicine at Karolinska Institutet in 2020, where she joined the Woll group for her master thesis. She was then working on a project regarding the impact of cell cycle of hematopoietic stem cells in normal and malignant hematopoiesis.

After graduating, she stayed in the Woll group as a PhD student where she is now exploring potential elimination of hematopoietic stem cells with TCR-engineered T cells to determine the dependency of HSCs in normal and malignant hematopoiesis.

Madde grew up spending all her spare time on the football field but now she also enjoys photography, playing golf and she spends as much time as possible with family and friends. If she is allowed to control the music during dinner parties, it's non-stop Swedish music with Thomas Stenström, Laleh and Mares streaming from the speakers.

Axel Winroth

PhD student
H7 Department of Medicine, Huddinge

Axel Winroth received his medical degree in January 2020 and joined the Woll lab shortly after.

His Phd project aims to investigate transcriptional states associated with lineage bias in hematopoietic stem cell differentiation using single cell RNA sequencing. In addition to stem cell biology he is interested in programming and mathematics and hopes to understand bioinformatics.

When not in the lab Axel enjoys drinking coffee and going for walks.

Collaborators

Karolinska Institutet

International collaborations

  • Johanna Olweus, Department of Cancer Immunology, Oslo University Hospital
  • Adam Mead, MRC Molecular Hematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford

Research support

  • Karolinska Institutet
  • Knut and Alice Wallenberg Foundation

Selected publications

2020-2021

T cells targeted to TdT kill leukemic lymphoblasts while sparing normal lymphocytes
Ali M, Giannakopoulou E, Li Y, Lehander M, Virding Culleton S, Yang W, Knetter C, Odabasi MC, Bollineni RC, Yang X, Foldvari Z, Böschen ML, Taraldsrud E, Strønen E, Toebes M, Hillen A, Mazzi S, de Ru AH, Janssen GMC, Kolstad A, Tjønnfjord GE, Lie BA, Griffioen M, Lehmann S, Osnes LT, Buechner J, Garcia KC, Schumacher TN, van Veelen PA, Leisegang M, Jacobsen SEW, Woll PS, Olweus J. 
Nature Biotechnology, 2021

Aged healthy mice acquire clonal hematopoiesis mutations.
Chin DWL, Yoshizato T, Virding Culleton S, Grasso F, Barbachowska M, Ogawa S, Jacobsen SEW, Woll PS
Blood 2021 Oct;(): #Equal contribution

Stem cell concepts in myelodysplastic syndromes: lessons and challenges.
Woll PS, Jacobsen SEW
J Intern Med 2021 05;289(5):650-661

A three-dimensional in vitro model of erythropoiesis recapitulates erythroid failure in myelodysplastic syndromes.
Elvarsdóttir EM, Mortera-Blanco T, Dimitriou M, Bouderlique T, Jansson M, Hofman IJF, Conte S, Karimi M, Sander B, Douagi I, Woll PS, Hellström-Lindberg E
Leukemia 2020 01;34(1):271-282

2018-2019

The concept of leukaemic stem cells in acute myeloid leukaemia 25 years on: hitting a moving target.
Hokland P, Woll PS, Hansen MC, Bill M
Br J Haematol 2019 10;187(2):144-156

Hierarchically related lineage-restricted fates of multipotent haematopoietic stem cells.
Carrelha J, Meng Y, Kettyle LM, Luis TC, Norfo R, Alcolea V, Boukarabila H, Grasso F, Gambardella A, Grover A, Högstrand K, Lord AM, Sanjuan-Pla A, Woll PS, Nerlov C, Jacobsen SEW
Nature 2018 02;554(7690):106-111

Canonical Notch signaling is dispensable for adult steady-state and stress myelo-erythropoiesis.
Duarte S, Woll PS, Buza-Vidas N, Chin DWL, Boukarabila H, Luís TC, Stenson L, Bouriez-Jones T, Ferry H, Mead AJ, Atkinson D, Jin S, Clark SA, Wu B, Repapi E, Gray N, Taylor S, Mutvei AP, Tsoi YL, Nerlov C, Lendahl U, Jacobsen SEW
Blood 2018 04;131(15):1712-1719

2010-2014

Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo.
Woll PS, Kjällquist U, Chowdhury O, Doolittle H, Wedge DC, Thongjuea S, Erlandsson R, Ngara M, Anderson K, Deng Q, Mead AJ, Stenson L, Giustacchini A, Duarte S, Giannoulatou E, Taylor S, Karimi M, Scharenberg C, Mortera-Blanco T, Macaulay IC, Clark SA, Dybedal I, Josefsen D, Fenaux P, Hokland P, Holm MS, Cazzola M, Malcovati L, Tauro S, Bowen D, Boultwood J, Pellagatti A, Pimanda JE, Unnikrishnan A, Vyas P, Göhring G, Schlegelberger B, Tobiasson M, Kvalheim G, Constantinescu SN, Nerlov C, Nilsson L, Campbell PJ, Sandberg R, Papaemmanuil E, Hellström-Lindberg E, Linnarsson S, Jacobsen SE
Cancer Cell 2014 Jun;25(6):794-808

Platelet-biased stem cells reside at the apex of the haematopoietic stem-cell hierarchy.
Sanjuan-Pla A, Macaulay IC, Jensen CT, Woll PS, Luis TC, Mead A, Moore S, Carella C, Matsuoka S, Bouriez Jones T, Chowdhury O, Stenson L, Lutteropp M, Green JC, Facchini R, Boukarabila H, Grover A, Gambardella A, Thongjuea S, Carrelha J, Tarrant P, Atkinson D, Clark SA, Nerlov C, Jacobsen SE
Nature 2013 Oct;502(7470):232-6

Persistent malignant stem cells in del(5q) myelodysplasia in remission.
Tehranchi R, Woll PS, Anderson K, Buza-Vidas N, Mizukami T, Mead AJ, Astrand-Grundström I, Strömbeck B, Horvat A, Ferry H, Dhanda RS, Hast R, Rydén T, Vyas P, Göhring G, Schlegelberger B, Johansson B, Hellström-Lindberg E, List A, Nilsson L, Jacobsen SE
N Engl J Med 2010 Sep;363(11):1025-37 #Equal contribution