Petter Woll group

Cellular and molecular mechanisms promoting establishment and propagation of leukemic stem cells

Photo: emmkar

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, and of particular in components involved in the regulation of mRNA splicing. 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.

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 these 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.

Members

Petter Woll

Group Leader, Ph.D., Assistant Professor

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, and 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 2015, Woll started as an Assistant Professor at the Karolinska Institutet where his lab that is located at the Center for Hematology and Regenerative Medicine is focused on unravelling cellular and molecular mechanisms underlying malignant hematopoiesis. In his spare time, he enjoys sports, including cycling, squash and skiing, and to go to concerts. His all-time top 5 favourite bands are (in no particular order): Bruce Springsteen, Radiohead, Åge Aleksandersen, The National and Nick Cave.

Francesca Grasso

Ph.D., Senior lab manager

Francesca received her MSc degree in Medical, molecular and cellular biotechnologies from Rome “La Sapienza” university in 2010 and her PhD in Biology applied to human health from “RomaTre” university with a fellowship sponsored by “Istituto Superiore di Sanitá” in 2015. For her postdoc she craved for an abroad experience which led her to Karolinska Institutet. Francesca joined Petter Woll’s group as lab manager at the Center for Hematology and Regenerative Medicine in 2017. Here she is refining her skills in the field of flow cytometry and she’s managing the FACS facility shared with Jacobsen group. In her spare time she enjoys travelling, doing yoga or swimming, watching movies and reading. She also loves listening to music such as Radiohead, Pearl Jam, Fabrizio de André, Rodrigo y Gabriela, Miles Davis.

Stina Virding

PhD Student

Stina Virding received her master degree in Biomedicine at Karolinska Institute in 2015. Before she started 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. Her 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 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 she enjoys skiing, sailing, dancing and playing tennis. Stina listens to all kind of music but some of her favourite bands include The Nationals, Bon Iver, First Aid Kit & Bo Kaspers Orkester.

Madeleine Lehander

PhD Student

Madeleine, 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

Axel 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.  

Contact information

Petter S. Woll, Group Leader, Assistant Professor
petter.woll@ki.se

Selected publications

Mortera-Blanco T, Dimitriou M, Woll PS, Karimi M, Elvarsdottir E, Conte S, Tobiasson M, Jansson M, Douagi I, Moarii M, Saft L, Papaemmanuil E, Jacobsen SEW, Hellström-Lindberg E. SF3B1-initiating mutations in MDS-RSs target lymphomyeloid hematopoietic stem cells. Blood 2017 130;7 881-890

Unnikrishnan A, Papaemmanuil E, Beck D, Deshpande NP, Verma A, Kumari A, Woll PS, Richards LA, Knezevic K, Chandrakanthan V, Thoms JAI, Tursky ML, Huang Y, Ali Z, Olivier J, Galbraith S, Kulasekararaj AG, Tobiasson M, Karimi M, Pellagatti A, Wilson SR, Lindeman R, Young B, Ramakrishna R, Arthur C, Stark R, Crispin P, Curnow J, Warburton P, Roncolato F, Boultwood J, Lynch K, Jacobsen SEW, Mufti GJ, Hellstrom-Lindberg E, Wilkins MR, MacKenzie KL, Wong JWH, Campbell PJ, Pimanda JE. Integrative Genomics Identifies the Molecular Basis of Resistance to Azacitidine Therapy in Myelodysplastic Syndromes. Cell reports 2017 20;3 572-585

Mead AJ, Neo WH, Barkas N, Matsuoka S, Giustacchini A, Facchini R, Thongjuea S, Jamieson L, Booth CAG, Fordham N, Di Genua C, Atkinson D, Chowdhury O, Repapi E, Gray N, Kharazi S, Clark SA, Bouriez T, Woll P, Suda T, Nerlov C, Jacobsen SEW. Niche-mediated depletion of the normal hematopoietic stem cell reservoir by Flt3-ITD-induced myeloproliferation. The Journal of experimental medicine 2017 214;7 2005-2021

Scharenberg C, Giai V, Pellagatti A, Saft L, Dimitriou M, Jansson M, Jädersten M, Grandien A, Douagi I, Neuberg DS, LeBlanc K, Boultwood J, Karimi M, Jacobsen SE, Woll PS, Hellström-Lindberg E. Progression in patients with low- and intermediate-1-risk del(5q) myelodysplastic syndromes is predicted by a limited subset of mutations. Haematologica 2017 102;3 498-508

Giustacchini A, Thongjuea S, Barkas N, Woll PS, Povinelli BJ, Booth CAG, Sopp P, Norfo R, Rodriguez-Meira A, Ashley N, Jamieson L, Vyas P, Anderson K, Segerstolpe Å, Qian H, Olsson-Strömberg U, Mustjoki S, Sandberg R, Jacobsen SEW, Mead AJ. Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia. Nature medicine 2017 23;6 692-702

Drissen R, Buza-Vidas N, Woll P, Thongjuea S, Gambardella A, Giustacchini A, Mancini E, Zriwil A, Lutteropp M, Grover A, Mead A, Sitnicka E, Jacobsen SEW, Nerlov C. Distinct myeloid progenitor-differentiation pathways identified through single-cell RNA sequencing. Nature immunology 2016 17;6 666-676

Dimitriou M, Woll PS, Mortera-Blanco T, Karimi M, Wedge DC, Doolittle H, Douagi I, Papaemmanuil E, Jacobsen SE, Hellström-Lindberg E. Perturbed hematopoietic stem and progenitor cell hierarchy in myelodysplastic syndromes patients with monosomy 7 as the sole cytogenetic abnormality. Oncotarget 2016 7;45 72685-72698

Bardini M, Woll PS, Corral L, Luc S, Wittmann L, Ma Z, Lo Nigro L, Basso G, Biondi A, Cazzaniga G, Jacobsen SE. Clonal variegation and dynamic competition of leukemia-initiating cells in infant acute lymphoblastic leukemia with MLL rearrangement. Leukemia 2015 29;1 38-50

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. Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo. Cancer cell 2014 25;6 794-808

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. Platelet-biased stem cells reside at the apex of the haematopoietic stem-cell hierarchy. Nature 2013 502;7470 232-6

Lutz C, Woll PS, Hall G, Castor A, Dreau H, Cazzaniga G, Zuna J, Jensen C, Clark SA, Biondi A, Mitchell C, Ferry H, Schuh A, Buckle V, Jacobsen SW, Enver T. Quiescent leukaemic cells account for minimal residual disease in childhood lymphoblastic leukaemia. Leukemia 2013 27;5 1204-1207

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. Persistent malignant stem cells in del(5q) myelodysplasia in remission. The New England journal of medicine 2010 363;11 1025-37 (*equal contribution)

Current active grants