Judith Zaugg, Anthony D. Ho, Carsten Müller-Tidow, Anne-Claude Gavin and Caroline Pabst

Judith Zaugg, Anthony D. Ho, Carsten Müller-Tidow, Anne-Claude Gavin and Caroline Pabst

Judith Zaugg, Caroline Pabst, Anthony D. Ho (emeritus group leader) and Carsten Müller–Tidow

Our research interest

Our research is focused on understanding the molecular and functional interactions between haematopoietic 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.

Background

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.

Goals

Our research focuses on three major aspects of HSC-niche interactions:

  • The 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.

Important Publications

Hepatic leukemia factor is a novel leukemic stem cell regulator in DNMT3A, NPM1, and FLT3-ITD triple-mutated AML.
Garg S, Reyes-Palomares A, He L, Bergeron A, Lavallée VP, Lemieux S, Gendron P, Rohde C, Xia J, Jagdhane P, Müller-Tidow C, Lipka DB, Imren S, Humphries RK, Waskow C, Vick B, Jeremias I, Richard-Carpentier G, Hébert J, Sauvageau G, Zaugg J, Barabé F, Pabst C.
Blood. 2019 May 10. pii: blood.2018862383. doi: 10.1182/blood.2018862383. [Epub ahead of print]
PMID: 31076446

Cell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline.
Hennrich ML, Romanov N, Horn P, Jaeger S, Eckstein V, Steeples V, Ye F, Ding X, Poisa-Beiro L, Lai MC, Lang B, Boultwood J, Luft T, Zaugg JB, Pellagatti A, Bork P, Aloy P, Gavin AC, Ho AD.
Nat Commun. 2018 Oct 1;9(1):4004. doi: 10.1038/s41467-018-06353-4. PMID:30275468

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