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Hong Qian group

Our missions: on research and education

1. To understand the role of mesenchymal niche in leukemia and tissue regeneration with the ultimate goal of identifying novel therapeutic strategies to improve treatment outcome in patients.

2. To build nourish niche for our team members to grow while creating a supportive niche for our research projects.

Our current research focus is on microenvironment/niche regulation of normal and malignant hematopoiesis. Hematopoiesis is generated and maintained by hematopoietic stem cells (HSCs) in bone marrow during postnatal life. This process is well controlled by a specialized microenvironment in bone marrow, the so-called HSC niche. The niche consists of various types of cellular niche elements including osteoblasts, adipocytes, endothelial cells, perivascular mesenchymal progenitor cells, mesenchymal stem cells (MSCs), as well as cytokines, growth factors produced by these cells.

There is increasing evidence showing that the niche also contributes to the development of myeloid malignancies and drug resistance of leukemia-initiating stem cells (LSCs) which maintain the disease and cause relapse. Thus, targeting the bone marrow niche may offer new therapeutic opportunities to improve the efficacy of current therapy for leukemia. However, so far, little is known about how the niche interacts with LSCs and contributes to disease initiation and progression.

The primary aim of our research is to understand bone marrow microenvironment/niche contribution to the development of myeloid leukemia including chronic myeloid leukemia (CML) and acute myeloid leukemia (AML) and treatment outcome in patients with the diseases by characterizing leukemia niche in patients and mice. The long-term goal is to identify the niche components that can serve as novel therapeutic targets and prognostic markers for myeloid leukemia.

The MSCs, as a precursor for mesenchymal lineages, play an important role in maintaining HSC niche homeostasis and remodeling leukemia niche. Therefore, deciphering the role of the MSCs in leukemia development and the underlying mechanisms is one of our research priorities.

In addition, unlike hematopoietic cells, the developmental hierarchy of mesenchymal cells has not been clearly defined. Understanding of this would provide important basis for further studying the physiological and pathological roles of different mesenchymal cell subsets. Thus, we also aim to dissect mesenchymal cell compartment from bone marrow.

Major techniques used in our projects: on patient materials and mouse models

  • Multi-colour flow cytometry (FACS),

  • RNA-sequencing, Q-PCR, single cell PCR, Fluorescence in situ hybridization,

  • ELISA,

  • Confocal imaging, immunohistochemistry,

  • In vivo stem cell fate-mapping using mouse models,

  • MSC assays: multilineage differentiation and expansion

  • In vivo and in vitro HSC assays: LTC-IC and Experimental transplantation.

Keywords: Mesenchymal stem cells, bone marrow, flow cytometry, transgenic mouse models, cell-cell interactions, hematopoiesis

Members

Hong Qian, Group Leader. Dr.

Hong Qian was recruited to Karolinska Institutet as an assistant professor in 2011. She received a Ph.D. degree in Stem Cell Biology from Lund University, Sweden (2007) and did a postdoc at Department of Clinical and Experimental Medicine, Linköping University, Sweden (2008-2011).

Phone: +46-8-524 834 53

Marja Ekblom, MD, PhD, Professor Emerita in Hematology

Dr. Marja Ekblom is Professor, Emerita in Hematology in the Department of Molecular Hematology, Lund University. She has worked in Skåne University Hospital as a senior hematologist with a special focus of chronic myeloid leukemia. Her preclinical research focus has been mainly in molecular hematology, including cell-cell/matrix interactions, in normal and malignant hematopoiesis.

Lakshmi Sandhow, PhD student

Lakshmi Sandhow joined Hong Qian group as a PhD student in 2015 after receiving a Master degree in Biomedicine from Karolinska Institute. Her study focuses on identification and characterization of mesenchymal stem cells (MSC) from different tissues including skin, bone marrow and adipose tissue. The aim is to understand natural phenotypes of the MSC and their role in tissue turnover. Beside her main project, she also participates in the study of bone marrow MSC during acute myeloid leukemia development in vivo.

Monika Dolinska, PhD student

She graduated as a Master of Science in Medical Biotechnology from University of Warsaw, Poland. She joined Dr. Hong Qian's Group in April 2014.

Yuchen Gao, master student

Yuchen received his B.S. degree in Biological Science from Virginia Tech, United States. He is pursuing his Master study in Biomedicine in Karolinska Institute. He is currently doing his thesis project in Dr. Qian's group.

Previous group members

Anne-Sofie Johansson, the lab manager, is currently working in Luc’group at HERM, KI.

Makoto Kondo, a postdoc, is currently working at College of Pharmacy, Utah, USA

Pingnan Xiao, obtained her PhD degree in 2017, is currently working at the first Affiliated Hospital of Zhejiang University, China

Thibault Bouderlique, was a postdoc, is currently working in Månsson’s group at HERM, KI.

Financial support

  • Wallenberg Institutet for Regenerative Medicine (WIRM)

  • Karolinska Institutet Research foundation (KI fonder)

  • The Swedish Cancer Society (Cancerfonden)

  • The Swedish Research Council (Vetenskapsrådet)

  • The Swedish Childhood Cancer Society (Barncancerfonden)

  • Radiumhemmets Forskningsfonder (The Cancer Research Foundations of Radiumhemmet)

  • Felix Mindus bidrag till leukemiforskningen

  • Dr. Åke Olsson foundation for hematological research

  • Stiftelsen Clas Groschinskys Minnesfond

  • The Incyte Nordic Grant for Hematological Research

Selected publications

Distinct roles of mesenchymal stem and progenitor cells during the development of acute myeloid leukemia in mice.
Xiao P, Sandhow L, Heshmati Y, Kondo M, Bouderlique T, Dolinska M, et al
Blood Adv 2018 06;2(12):1480-1494

Sipa1 deficiency-induced bone marrow niche alterations lead to the initiation of myeloproliferative neoplasm
Xiao P, Dolinska M, Sandhow L, Kondo M, Johansson AS, Bouderlique T, Zhao Y, Li X, Dimitriou M, Rassidakis G, Hellström-Lindberg E, Minato N, Walfridsson J, Scadden DT, Sigvardsson M, Qian H.
Blood Adv. 2018 Mar 13;2(5):534-548

The chromatin-remodeling factor CHD4 is required for maintenance of childhood acute myeloid leukemia.
Heshmati Y, Türköz G, Harisankar A, Kharazi S, Boström J, Dolatabadi E, et al
Haematologica 2018 07;103(7):1169-1181

The histone chaperone NAP1L3 is required for haematopoietic stem cell maintenance and differentiation.
Heshmati Y, Kharazi S, Türköz G, Chang D, Kamali Dolatabadi E, Boström J, et al
Sci Rep 2018 Jul;8(1):11202

CD36 Is a Marker of Human Adipocyte Progenitors with Pronounced Adipogenic and Triglyceride Accumulation Potential.
Gao H, Volat F, Sandhow L, Galitzky J, Nguyen T, Esteve D, et al
Stem Cells 2017 07;35(7):1799-1814

Leukotriene signaling via ALOX5 and cysteinyl leukotriene receptor 1 is dispensable for in vitro growth of CD34CD38 stem and progenitor cells in chronic myeloid leukemia.
Dolinska M, Piccini A, Wong W, Gelali E, Johansson A, Klang J, et al
Biochem. Biophys. Res. Commun. 2017 08;490(2):378-384

Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia.
Giustacchini A, Thongjuea S, Barkas N, Woll P, Povinelli B, Booth C, et al
Nat. Med. 2017 Jun;23(6):692-702

A novel Lin-CD34+CD38- integrin α2- bipotential megakaryocyte-erythrocyte progenitor population in the human bone marrow.
Wong W, Dolinska M, Sigvardsson M, Ekblom M, Qian H
Leukemia 2016 06;30(6):1399-402

Amniotic fluid - a source for clinical therapeutics in the newborn?
Ekblad �, Qian H, Westgren M, Le Blanc K, Fossum M, Götherström C
Stem Cells Dev. 2015 Jun;24(12):1405-14

Yan HJ, Oommen OP, Yu D, Hilborn J, Qian H, Varghese OP.
Chondroitin Sulfate-Coated DNA-Nanoplexes Enhance Transfection Efficiency by Controlling Plasmid Release from Endosomes: A New Insight into Modulating Nonviral Gene Transfection.
ADVANCED FUNCTIONAL MATERIALS 2015 25;25 3907-3915.

Immune challenge by intraperitoneal administration of lipopolysaccharide directs gene expression in distinct blood-brain barrier cells toward enhanced prostaglandin E(2) signaling.
Vasilache A, Qian H, Blomqvist A
Brain Behav. Immun. 2015 Aug;48():31-41

Early B-cell factor 1 regulates the expansion of B-cell progenitors in a dose-dependent manner.
Åhsberg J, Ungerbäck J, Strid T, Welinder E, Stjernberg J, Larsson M, et al
J. Biol. Chem. 2013 Nov;288(46):33449-61

Expression of integrin α2 receptor in human cord blood CD34+CD38-CD90+ stem cells engrafting long-term in NOD/SCID-IL2Rγ(c) null mice.
Wong W, Sigvardsson M, Åstrand-Grundström I, Hogge D, Larsson J, Qian H, et al
Stem Cells 2013 Feb;31(2):360-71

Molecular characterization of prospectively isolated multipotent mesenchymal progenitors provides new insight into the cellular identity of mesenchymal stem cells in mouse bone marrow.
Qian H, Badaloni A, Chiara F, Stjernberg J, Polisetti N, Nihlberg K, et al
Mol. Cell. Biol. 2013 Feb;33(4):661-77

Lipopolysaccharide-induced fever depends on prostaglandin E2 production specifically in brain endothelial cells.
Engström L, Ruud J, Eskilsson A, Larsson A, Mackerlova L, Kugelberg U, et al
Endocrinology 2012 Oct;153(10):4849-61

Primary mesenchymal stem and progenitor cells from bone marrow lack expression of CD44 protein.
Qian H, Le Blanc K, Sigvardsson M
J. Biol. Chem. 2012 Jul;287(31):25795-807

Single-cell analysis of early B-lymphocyte development suggests independent regulation of lineage specification and commitment in vivo.
Zandi S, Ahsberg J, Tsapogas P, Stjernberg J, Qian H, Sigvardsson M
Proc. Natl. Acad. Sci. U.S.A. 2012 Sep;109(39):15871-6

IL-7 mediates Ebf-1-dependent lineage restriction in early lymphoid progenitors.
Tsapogas P, Zandi S, Åhsberg J, Zetterblad J, Welinder E, Jönsson J, et al
Blood 2011 Aug;118(5):1283-90

Genomics based analysis of interactions between developing B-lymphocytes and stromal cells reveal complex interactions and two-way communication.
Zetterblad J, Qian H, Zandi S, Månsson R, Lagergren A, Hansson F, et al
BMC Genomics 2010 Feb;11():108

Interleukin-7-induced Stat-5 acts in synergy with Flt-3 signaling to stimulate expansion of hematopoietic progenitor cells.
Åhsberg J, Tsapogas P, Qian H, Zetterblad J, Zandi S, Månsson R, et al
J. Biol. Chem. 2010 Nov;285(47):36275-84

Stabilins are expressed in bone marrow sinusoidal endothelial cells and mediate scavenging and cell adhesive functions.
Qian H, Johansson S, McCourt P, Smedsrød B, Ekblom M, Johansson S
Biochem. Biophys. Res. Commun. 2009 Dec;390(3):883-6

Kit regulates maintenance of quiescent hematopoietic stem cells.
Thorén L, Liuba K, Bryder D, Nygren J, Jensen C, Qian H, et al
J. Immunol. 2008 Feb;180(4):2045-53

Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells.
Qian H, Buza-Vidas N, Hyland C, Jensen C, Antonchuk J, Månsson R, et al
Cell Stem Cell 2007 Dec;1(6):671-84

Distinct roles of integrins alpha6 and alpha4 in homing of fetal liver hematopoietic stem and progenitor cells.
Qian H, Georges-Labouesse E, Nyström A, Domogatskaya A, Tryggvason K, Jacobsen S, et al
Blood 2007 Oct;110(7):2399-407

17433729

Contribution of alpha6 integrins to hematopoietic stem and progenitor cell homing to bone marrow and collaboration with alpha4 integrins.
Qian H, Tryggvason K, Jacobsen S, Ekblom M
Blood 2006 May;107(9):3503-10

Cytokines regulate postnatal hematopoietic stem cell expansion: opposing roles of thrombopoietin and LNK.
Buza-Vidas N, Antonchuk J, Qian H, Månsson R, Luc S, Zandi S, et al
Genes Dev. 2006 Aug;20(15):2018-23

Group news: Trainee presentations and awards

Oral presentations at international conferences

  • Pingnan Xiao gave an oral presentation at the at the 56th ASH Annual meeting, San Francisco, USA in 2014.
  • Monika Dolinska gave an oral presentation at the 17th John Goldman CML conference, in 2015, Estoril, Portugal.
  • Lakshmi Sandhow gave an oral presentation at ISSCR conference in 2015, in Stockholm, Sweden.
  • Monika Dolinska gave an oral presentation at the ESH MSC conference, in 2017, Amsterdam.
  • Makoto Kondo gave an oral presentation at the 58th ASH meeting, San Diego, USA. 2016.
  • Lakshmi Sandhow gave an oral presentation at the ISSCR conference in June 2018, Melbourne, Australia.

Student Awards

  1. The 56th ASH abstract achievement award to Pingnan Xiao in 2014.
  2. The 58th ASH abstract achievement award to Makoto Kondo in 2016.
  3. The Incyte Award to Monika Dolinska in 2018.
  4. Travel award from International Stem Cell Research (ISSCR) to Lakshmi Sandhow in 2018.
  5. Student award from Mayo Clinc for the 8th Mayo Clinic Symposium on Tumor Microenvironment and Cancer Therapeutics at Jacksonville, FL, USA, in 2018.

Open positions

We always want to get in touch with talented potential co-workers. If you are interested in doing research within our group, as a degree project or as a researcher, please contact the group leader Hong Qian.