The Nilsson Group is currently involved in a number of research projects that focus on understanding haemopoietic stem cells (HSC). Haemopoietic stem cells are responsible for the production of blood and immune cells.

They are a very important part of the body as they are constantly renewing blood. They create billions of new blood cells each day. They are located in the bone marrow, which is the flexible tissue inside most bones. 


Research

The main objective of the group’s research is to characterise the microenvironment in which blood stem cells reside. They also look at blood stems cells at a cellular and molecular level, as well as analysing how they create new blood cells. 

Learning more about normal and diseased stem cells will lead to better prevention, clinical diagnosis and treatment. This will ultimately improve human health. An example of this is better bone marrow transplantation outcomes in cancer patients because they will be able to replace normal cells that are destroyed during anticancer therapy. Essentially, it will allow higher doses of chemotherapy or radiation to be given which will be a more effective form of treatment.

 

Nilsson group members
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  • Understanding the role of the endosteal niche in the regulation and function of haemopoietic stem cells
  • Characterising the role of megakaryocytes in the endosteal niche and haemopoietic stem cell regulation
  • Isolating bone marrow sinusoidal endothelial cells and characterising their role and potential
  • Understanding the role of key extracellular matrix molecules in the adult bone marrow microenvironment in foetal haemopoietic development
  •  Design and synthesis of novel haemopoietic stem cell mobilisation agents
  • Characterising adult cells that have been directly differentiated into hemopoietic stem cells. 
  • Functionally assessing embryonic stem cell subpopulations whose differentiation has been directed towards hemopoietic stem cells.
     

Featured Publications

More Publications

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Sheikh BN, Yang Y, Schreuder J, Nilsson SK, Bilardi R, Carotta S, McRae HM, Metcalf D, Voss AK, Thomas T.

MOZ (KAT6A) is essential for the maintenance of classically defined adult hematopoietic stem cells.
 

Blood. 2016 Sep 23. pii: blood-2015-10-676072. [Epub ahead of print]

Le Texier L, Lineburg KE, Cao B, McDonald-Hyman C, Leveque-El Mouttie L, Nicholls J, Melino M, Nalkurthi BC, Alexander KA, Teal B, Blake SJ, Souza-Fonseca-Guimaraes F, Engwerda CR, Kuns RD, Lane SW, Teng M, Teh C, Gray D, Clouston AD, Nilsson SK, Blazar BR, Hill GR, MacDonald KP.

Autophagy-dependent regulatory T cells are critical for the control of graft-versus-host disease.

JCI Insight. 2016 Sep 22;1(15):e86850.

Griffiths K, Pfleger KDG, Dolezal O, Cao B, Nilsson SK, Pow A, Kvansakul M, Roche M, Perugini M, Dogovski C, Dorflinger M, Zhang Y, Gorry P, Lim K, Lu B, Chang D, Viduka K, Murray-Rust T, Parisi K, Casey J, Nuttall S, Foley M.

I-bodies: human single domain antibodies that selectively antagonize chemokine receptor CXCR4.

J Biol Chem. 2016 Jun 10;291(24):12641-57. doi: 10.1074/jbc.M116.721050. Epub 2016 Apr 1.

Cao B, Zhang Z, Grassinger J, Williams B, Heazlewood CK, Churches QI, James SA, Li S, Papayannopoulou T, Nilsson SK.

Therapeutic targeting and rapid mobilization of endosteal HSC using a small molecule integrin antagonist.

Nat Commun. 2016 Mar 15;7:11007. doi: 10.1038/ncomms11007.

Chalmers BA, Xing H, Houston S, Clark C, Ghassabian S, Kuo A, Cao B, Reitsma A, Murray CE, Stok JE, Boyle GM, Pierce CJ, Littler SW,Winkler DA, Bernhardt PV, Pasay C, De Voss JJ, McCarthy J, Parsons PG, Walter GH, Smith MT, Cooper HM, Nilsson SK, Tsanaktsidis J,Savage GP, Williams CM.

Validating Eaton's Hypothesis: Cubane as a Benzene Bioisostere.

Angew Chem Int Ed Engl. 2016 Mar 7;55(11):3580-5. doi: 10.1002/anie.201510675. Epub 2016 Feb 5.

Cao H, Cardozo D, Nigro J, Oteiza A, Nilsson SK.

The role of CD44 in hemopoietic stem cell regulation during ontogeny.

Haematol. 2016 Jan;101: 26-37. doi:10.3324/haematol.2015.135921.

Storan MJ, Heazlewood SY, Heazlewood CK, Haylock DN, Neaves RJ, Alexander WS, Oteiza A, Nilsson SK.

Megakaryocytes release factors required to thrombin cleave osteopontin, allowing for the negative regulation of hemopoietic stem cells.

Stem Cells. 2015 Jul;33(7):2351-7. doi: 10.1002/stem.2038. Epub 2015 May 15. Impact Factor: 6.523. Ranking: 10/162.

Liang K, Ricco R, Doherty CM, Styles MJ, Bell S, Kirby N, Mudie S, Haylock D, Hill AJ, Doonan CJ, Falcaro P.

Biomimetic mineralization of metal-organic frameworks as protective coatings for biomacromolecules.

Nat Commun. 2015 Jun 4;6:7240. doi: 10.1038/ncomms8240. Impact Factor: 11.470. Ranking: 3/56.

Muerza-Cascante ML, Haylock D, Hutmacher DW, Dalton PD.

Melt electrospinning and its technologization in tissue engineering.

Tissue Eng Part B Rev. 2015 Apr;21(2):187-202. doi: 10.1089/ten.TEB.2014.0347. Epub 2014 Dec 18.

Lee EJ, Be CL, Vinson AR, Riches AG, Fehr F, Gardiner J, Gengenbach TR, Winkler DA, Haylock D.

Immobilisation of a thrombopoietin peptidic mimic by self-assembled monolayers for culture of CD34+ cells.

Biomaterials. 2015 Jan;37:82-93. doi: 10.1016/j.biomaterials.2014.10.029. Epub 2014 Oct 23. Impact Factor: 8.557. Ranking: 2/76.

Henderson TM, Ladewig K, Haylock DN, McLean KM, O'Connor AJ.

Formation and characterisation of a modifiable soft macro-porous hyaluronic acid cryogel platform.

J Biomater Sci Polym Ed. 2015;26(13):881-97. doi: 10.1080/09205063.2015.1065597. Impact Factor: 1.648. Ranking: 42/76.

McCourt PA, Oteiza A, Cao B, Nilsson SK.

Isolation of murine bone marrow scavenging sinusoidal endothelial cells.

Methods Mol Biol. 2015;1235:59-71. doi: 10.1007/978-1-4939-1785-3_6.

Soh CL, Giudice A, Jenny RA, Elliot DA, Hatzistavrou T, Micallef SJ, Kianizad K, Seach N, Zuniga-Pflucker JC, Chidgey AP, Trounson A, Nilsson SK, Haylock DN, Boyd RL, Elefanty AG, Stanley EG.

FOXN1 (GFP/w) Reporter hESCs Enable Identification of Integrin-beta4, HLA-DR, and EpCAM as Markers of Human PSC-Derived FOXN1(+) Thymic Epithelial Progenitors.

Stem Cell Reports. 2014 May 22;2(6):925-37. doi: 10.1016/j.stemcr.2014.04.009. eCollection 2014.

Cao B, Grassinger J, Williams B, Li S, Savage GP, Haylock DN, Hutt OE, Nilsson SK.

Dual α4β1/α9β1 integrin antagonists preferentially bind and mobilize hemopoietic stem cells from endosteal bone marrow.

Org and Biomol Chem. 2014;12:965-978.

Cao B, Hutt OE, Zhang Z, Li S, Heazlewood SY, Williams B, Smith JA, Haylock Dn, Savage GP, Nilsson SK.

Design, synthesis and binding properties of a fluorescent alpha(9)beta(1)/alpha(4)beta(1) integrin antagonist and its application as an in vivo probe for bone marrow haemopoietic stem cells.

Org Biomol. Chem 2014;12(6):965-978.

Ellis SL, Heazelwood SY, Williams B, Borg J, Reitsma AJ, Heazlewood CK, Chidgey AP, Nilsson SK.

The role of Tenascin C in anchoring lymphoid progenitor cells within their niche.

Exp Hematol 2013 Dec 29;41(12):1050-61. Epub 2013 Sep 29.

Cao H, Nilsson SK.

Understanding the role of the microenvironment during definitive hemopoietic development.

Exp Hematol. 2013 Sep;41(9):761-8. doi: 10.1016/j.exphem.2013.06.005. Epub 2013 Jun 22.

Shen Y, CK Heazlewood, Williams B, Neaves R, Haylock DN, McCourt P, Adams T, Nilsson SK.

Megakaryocytes are a key niche component, regulating hemopoietic stem cell proliferation through cytokine release.

Stem Cell Res. 2013 Sep;11(2):782-92. doi: 10.1016/j.scr.2013.05.007. Epub 2013 May 28.

Jähnichen S, Blanchetot C, Maussang D, Gonzalez-Pajuelo M, Chow KY, Bosch L, De Vrieze S, Serruys B, Ulrichts H, Vandevelde W, Saunders M, De Haard HJ, Schols D, Leurs R, Vanlandschoot P, Verrips T, Smit MJ.

CXCR4 nanobodies (VHH-based single variable domains) potently inhibit chemotaxis and HIV-1 replication and mobilize stem cells.

Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20565-70. doi: 10.1073/pnas.1012865107. Epub 2010 Nov 8.

Grassinger J, Haylock DN, Williams B, Olsen GH, Nilsson SK.

Phenotypically identical Hemopoietic Stem Cells isolated from different regions of bone marrow have different biological potential.

Blood. 2010 Oct 28;116(17):3185-96. doi: 10.1182/blood-2009-12-260703. Epub 2010 Jul 14.

Grassinger J, Haylock DN, Storan M, Haines GO, Williams B, Whitty GA, Vinson A, Be CL, Li S, Sørensen ES, Tam PL, Denhardt DT, Sheppard D, Choong PF, Nilsson SK.

Thrombin-cleaved osteopontin regulates hemopoietic stem and progenitor cell functions through interactions with alpha9beta1 and alpha4beta1 integrins.

Blood. 2009 Jul 2;114(1):49-59. doi: 10.1182/blood-2009-01-197988. Epub 2009 May 5.

Nilsson SK, Johnston HM, Whitty GA, Williams B, Webb RJ, Denhardt DT, Bertoncello I, Bendall LJ, Simmons PJ, Haylock DN.

Osteopontin, a key component of the hematopoietic stem cell niche and negative regulator of primitive hematopoietic progenitor cells.

Blood. 2005 Aug 15;106(4):1232-9. Epub 2005 Apr 21.

Nilsson SK, Haylock DN, Johnston HM, Occhiodoro T, Brown TJ, Simmons PJ.

Hyaluronan is synthesised by primitive hemopoietic cells, participates in their lodgement at the endosteum following transplantation and is involved in the regulation of their proliferation and differentiation in vitro.

Blood. 2003 Feb 1;101(3):856-62. Epub 2002 Sep 12.

Hou Z, Nguyen Q, Frenkel B, Nilsson SK, Milne M, Van Wijnen A, Stein JL, Quesenberry P, Lian JB, Stein GS.

Osteoblast-specific gene expression after transplantation of marrow cells: Implications for skeletal gene therapy.

Proc. Natl. Acad. Sci. USA 96(13):7294-7299.

Nilsson SK, Dooner MS, Weier H-U, Frenkel B, Lian JB, Stein GS, Quesenberry PJ.

Cells capable of bone production engraft from whole bone marrow transplants in nonablated mice.

J. Exp. Med. 189(4):729-734. doi: 10.1084/jem.189.4.729

Begg SK, Pollard JW, Radley JM, Chisholm OT, Stanley ER, Bertoncello I.

Delayed hematopoietic development in the osteopetrotic (op/op) mouse.

J Exp Med. 1993 Jan 1;177(1):237-42.