Julian Walfridsson group - Acute myeloid leukemia (AML)
Acute myeloid leukemia (AML) is an aggressive hematological disorder with dismal prognosis. Consequently, there is an unmet medical need to achieve increased understanding of factors and effectors that drives the disease and to develop effective and targeted treatments with acceptable side effects.
About our research
The main focus of our research is to discover factors and pathways that represent potential drug targets in AML and to delineate the underlying molecular mechanisms by which they are involved in pathogenesis. With this objective we use functional genomic techniques, in vivo models, patient derived cells and cell- and molecular biology techniques.
Acute myeloid leukemia (AML) is an aggressive blood cancer and less than 20% of adults and only about 60% of the children are cured of their disease, highlighting the urgent need of more effective treatment strategies.
Although the mechanisms of the disease remain incompletely understood, it is well established that cooperating genetic and epigenetic alterations contribute to AML pathogenesis. Various studies have demonstrated that individual AML tumor samples contain several hundreds to thousands of different gene mutations. The consequence of these genetic and epigenetic alterations is a widespread transcriptional deregulation of gene expression that give the cancer cells a proliferative growth advantage compared to normal cells. For the vast majority of these abnormalities it is not known which genes or downstream regulatory pathways that contribute to the initiation, maintenance and development of AML.
Current projects in our research group aims to identify and characterize novel biologically and clinically relevant genes with a role in AML pathogenesis and maintenance.
The projects aim to:
- Identify and characterize novel “druggable” epigenetic target genes that can serve as potential therapeutic targets to battle AML.
- Functionally annotate the causative mutations that are involved in AML pathogenesis.
- Determine the underlying molecular mechanisms by which the identified target genes contribute to AML pathogenesis and tumor expansion.
Towards these goals, we have established a cutting-edge technical and methodological platform, including flow cytometry, genome-wide mapping and analysis of epigenetic modifications (ChIP-sequencing and MeDIP-Seq), large-scale genetic screening systems, patient-derived AML cells and in vivo AML model systems. The ultimate aim is that the proposed strategy can lead to the discovery of relevant drug targets that can facilitate the development of novel therapeutic interventions in AML treatment.
AML, RNAi screening, functional genomics, epigenetics, in vivo cancer models, molecular mechanisms
Julian WalfridssonGroup Leader, Ph.D., Assistant Professor
Dr. Walfridsson was recruited to Karolinska Institutet as an assistant professor in 2011. He holds a Ph.D. degree in Cell and Molecular Biology at Karolinska Institutet, Sweden (2000) and did a postdoc at the Biotech Research Innovation Centre (BRIC), University of Copenhagen, Denmark (2007-2010).
Joanna Zawacka-PankauSenior Researcher / Team Leader
Dr. Joanna Zawacka-Pankau was recruited to Karolinska Institutet as Assistant Professor in 2012.
She has a PhD in biochemistry from University of Gdansk, Poland (2005) and completed her postdoctoral training at the Department of Microbiology, Tumor and Cell biology (2005 – 2007).
- Wallenberg Institute for Regenerative Medicine (WIRM)
- Åke Wibergs Stiftelse
- Magnus Bergvalls Stiftelse
- Åke Olssons Stiftelse
shRNA screening identifies JMJD1C as being required for leukemia maintenance.
Sroczynska P, Cruickshank VA, Bukowski JP, Miyagi S, Bagger FO, Walfridsson J, Schuster MB, Porse B, Helin K
Blood 2014 Mar;123(12):1870-82
The FUN30 chromatin remodeler, Fft3, protects centromeric and subtelomeric domains from euchromatin formation.
Strålfors A, Walfridsson J, Bhuiyan H, Ekwall K
PLoS Genet 2011 Mar;7(3):e1001334
A chromatin-remodeling protein is a component of fission yeast mediator.
Khorosjutina O, Wanrooij PH, Walfridsson J, Szilagyi Z, Zhu X, Baraznenok V, Ekwall K, Gustafsson CM
J Biol Chem 2010 Sep;285(39):29729-37
Characterization of an antagonistic switch between histone H3 lysine 27 methylation and acetylation in the transcriptional regulation of Polycomb group target genes.
Pasini D, Malatesta M, Jung HR, Walfridsson J, Willer A, Olsson L, Skotte J, Wutz A, Porse B, Jensen ON, Helin K
Nucleic Acids Res 2010 Aug;38(15):4958-69
JARID2 regulates binding of the Polycomb repressive complex 2 to target genes in ES cells.
Pasini D, Cloos PA, Walfridsson J, Olsson L, Bukowski JP, Johansen JV, Bak M, Tommerup N, Rappsilber J, Helin K
Nature 2010 Mar;464(7286):306-10
ATAD2 is a novel cofactor for MYC, overexpressed and amplified in aggressive tumors.
Ciró M, Prosperini E, Quarto M, Grazini U, Walfridsson J, McBlane F, Nucifero P, Pacchiana G, Capra M, Christensen J, Helin K
Cancer Res 2009 Nov;69(21):8491-8
A genome-wide role for CHD remodelling factors and Nap1 in nucleosome disassembly.
Walfridsson J, Khorosjutina O, Matikainen P, Gustafsson CM, Ekwall K
EMBO J 2007 Jun;26(12):2868-79
Interaction of Epe1 with the heterochromatin assembly pathway in Schizosaccharomyces pombe.
Isaac S, Walfridsson J, Zohar T, Lazar D, Kahan T, Ekwall K, Cohen A
Genetics 2007 Apr;175(4):1549-60
Genome-wide studies of histone demethylation catalysed by the fission yeast homologues of mammalian LSD1.
Opel M, Lando D, Bonilla C, Trewick SC, Boukaba A, Walfridsson J, Cauwood J, Werler PJ, Carr AM, Kouzarides T, Murzina NV, Allshire RC, Ekwall K, Laue ED
PLoS One 2007 Apr;2(4):e386
The CHD remodeling factor Hrp1 stimulates CENP-A loading to centromeres.
Walfridsson J, Bjerling P, Thalen M, Yoo EJ, Park SD, Ekwall K
Nucleic Acids Res 2005 ;33(9):2868-79
Dicer is required for chromosome segregation and gene silencing in fission yeast cells.
Provost P, Silverstein RA, Dishart D, Walfridsson J, Djupedal I, Kniola B, Wright A, Samuelsson B, Radmark O, Ekwall K
Proc Natl Acad Sci U S A 2002 Dec;99(26):16648-53