Judith Zaugg, Anthony D. Ho, Carsten Müller-Tidow, Anne-Claude Gavin and Caroline Pabst
Anne-Claude Gavin, Judith Zaugg and Caroline Pabst, Anthony D. Ho (emeritus group leader), Carsten Müller–Tidow
Our research interest
Our research is focused on understanding the molecular and functional interactions between hematopoietic stem cells (HSCs) and the bone marrow niche. We primarily use the most plastic niche cell population, mesenchymal stroma cells (MSCs), to model HSC-stroma cell interactions in vitro. We are specifically interested in understanding the role of MSCs in acute myeloid leukaemia (AML), and how changes in HSC-niche interactions during ageing might contribute to leukaemic transformation.
Bone marrow harbours different types of stem cells comprising HSCs, which give rise to all blood cells, and MSCs, which can differentiate into different stroma cell types. MSCs play a pivotal role in maintaining normal HSC functions such as survival, quiescence, proliferation and differentiation.
Our previous work has focused on understanding the pathogenesis of AML. AML is characterised by a rather small number of disease inducing mutations and multiple epigenetic changes. Results from our groups and others point towards the niche as an essential player in AML pathogenesis. Interactions between leukaemic stem cells and the niche are likely to impact on disease initiation, maintenance and therapy response.
We are combining computational biology, multi-omics methods, co-culture systems of primary human cells, and xenotransplantations to study the mutual impact of the different cell types on each other during ageing and leukaemia development.
Our research focuses on three major aspects of HSC-niche interactions:
- Role of ageing-related changes in stem cell-niche interactions in the development of haematological malignancies.
- Stem cell-niche communication in genetically defined AML subgroups.
- The differential impact of distinct sources of donor HSCs on the recipient bone marrow niche.
AML1-ETO requires enhanced C/D box snoRNA/RNP formation to induce self-renewal and leukaemia. Zhou F, Liu Y, Rohde C, Pauli C, Gerloff D, Köhn M, Misiak D, Bäumer N, Cui C, Göllner S, Oellerich T, Serve H, Garcia-Cuellar MP, Slany R, Maciejewski JP, Przychodzen B, Seliger B, Klein HU, Bartenhagen C, Berdel WE, Dugas M, Taketo MM, Farouq D, Schwartz S, Regev A, Hébert J, Sauvageau G, Pabst C, Hüttelmaier S, Müller-Tidow C.
Nat Cell Biol. 2017 Jul;19(7):844-855. doi: 10.1038/ncb3563. Epub 2017 Jun 26. PMID:28650479
Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia.
Göllner S, Oellerich T, Agrawal-Singh S, Schenk T, Klein HU, Rohde C, Pabst C, Sauer T, Lerdrup M, Tavor S, Stölzel F, Herold S, Ehninger G, Köhler G, Pan KT, Urlaub H, Serve H, Dugas M, Spiekermann K, Vick B, Jeremias I, Berdel WE, Hansen K, Zelent A, Wickenhauser C, Müller LP, Thiede C, Müller-Tidow C.
Nat Med. 2017 Jan;23(1):69-78. doi: 10.1038/nm.4247. Epub 2016 Dec 12. PMID: 27941792
GPR56 identifies primary human acute myeloid leukemia cells with high repopulating potential in vivo.
Pabst C, Bergeron A, Lavallée VP, Yeh J, Gendron P, Norddahl GL, Krosl J, Boivin I, Deneault E, Simard J, Imren S, Boucher G, Eppert K, Herold T, Bohlander SK, Humphries K, Lemieux S, Hébert J, Sauvageau G, Barabé F.
Blood. 2016 Apr 21;127(16):2018-27. doi: 10.1182/blood-2015-11-683649. Epub 2016 Feb 1. PMID: 26834243
SNPhood: investigate, quantify and visualise the epigenomic neighbourhood of SNPs using NGS data. Arnold C, Bhat P, Zaugg JB.
Bioinformatics. 2016 Aug 1;32(15):2359-60. doi: 10.1093/bioinformatics/btw127. Epub 2016 Mar 26. PMID:27153574
Genetic Control of Chromatin States in Humans Involves Local and Distal Chromosomal Interactions. Grubert F, Zaugg JB, Kasowski M, Ursu O, Spacek DV, Martin AR, Greenside P, Srivas R, Phanstiel DH, Pekowska A, Heidari N, Euskirchen G, Huber W, Pritchard JK, Bustamante CD, Steinmetz LM, Kundaje A, Snyder M.
Cell. 2015 Aug 27;162(5):1051-65. doi: 10.1016/j.cell.2015.07.048. Epub 2015 Aug 20. PMID: 26300125
Identification of small molecules that support human leukemia stem cell activity ex vivo.
Pabst C, Krosl J, Fares I, Boucher G, Ruel R, Marinier A, Lemieux S, Hébert J, Sauvageau G.
Nat Methods. 2014 Apr;11(4):436-42. doi: 10.1038/nmeth.2847. Epub 2014 Feb 23. PMID: 24562423
Research group's MMPU link to University Hospital web page