Kalle Malmberg group
The group study the molecular and cellular basis for NK cell differentiation and repertoire formation in health and disease. A key focus is to gain insights into how killer cell immunoglobulin-like receptors (KIR) influence the function of human NK cells. KIR are HLA class I binding receptors with important functions in reproduction, immunity to infections, and in cell therapy against cancer.
We examine the dynamic shaping of human NK cell repertoires during viral infection, tumor transformation and following stem cell transplantation. We are also seeking to implement new insights into the adaptive-like behaviour of NK cells in the next generation of NK cell-based immunotherapy for patients with refractory or relapsing malignancies.
Keywords: NK cells, killer cell immunoglobulin-like receptors, KIR, allogeneic hematopoietic stem cell transplantation, immunotherapy, cell therapy
The research group is mainly based at the Norwegian Radium Hospital and Oslo University. However, the group has a node at the Karolinska Institutet and maintain strong interactions with three research networks at the Karolinska Institutet:
- Immunomodulatory Therapies for Autoimmity and Cancer (IMTAC)
- Theme Center for Regenerative Medicine
- Center for Infectious Medicine (CIM)
The PI and some group members have double affiliation to CIM.
Karl-Johan Malmberg, Group Leader, M.D., Ph.D., Professor
|Kishan Chudasam, Post-doc, Ph.D. (OUS/UiO)|
|Ebba Sohlberg, Post-doc, Ph.D. (KI)|
|Merete Thune Wiiger, Biomedical assistant, (OUS)|
|Julie Hoel, Biomedical assistant, (OUS)|
Lisa Liu, Ph.D. student, (KI)
|Andreas Björklund, Post-doc, M.D. (KI)|
|Vincent Oei Sheng, Ph.D. student, (Oslo)|
|Eivind Heggernes Ask, Master student, (Forskerlinjen)|
|Michelle Sætersmoen, Ph.D. student (OUS)|
|Axel Berg-Larsen, Post-doc (OUS)|
|Trevor Clancy , Post-doc Bioinformatcs (OUS)|
|Jodie Goodridge, Senior Scientist (OUS)|
|Monika Enqvist, Ph.D student (KI)|
|Aline Pfefferle, Ph.D student (KI)|
|Mattias Carlsten (currently post-doc in Child Lab at NIH)|
|Cyril Fauriat (currently senior scientist in Marseille)|
|Vivien Beziat (currently post-doc in Cassanova Lab in Paris)|
NK Cell Therapy for Hematological Malignancies
The goal of the translational research program is to develop cellular therapies for hematological malignancies based on new insights into the biology and function of natural killer (NK) cells.
The research program is built around four specific aims:
- To identify principles for receptor acquisition and education of human NK cells
- To gain insights into the reconstitution of NK cell function and receptor repertoires following allogeneic stem cell transplantation
- To decode receptor-ligand interactions responsible for NK cell targeting of hematological malignancies
- To develop clinical protocols for cell and gene-therapy with NK cells
- Swedish Research Council
- the Swedish Cancer Society
- the Swedish Children´s Cancer Foundation
- the Cancer Society of Stockholm
- the Royal Swedish Academy of Sciences
- Stockholm City Council (ALF)
The group is a member of a virtual institute for developing innovative immune-based treatment approaches: Immunomodulatory Therapies for Autoimmity and Cancer (IMTAC). IMTAC recently received a 6-year grant to strengthen translational and clinical research at Karolinska Institutet.
The research on hematopoietic stem cell transplantation is supported by a joint grant to a "Theme Center for Regenerative Medicine".
Selenite induces posttranscriptional blockade of HLA-E expression and sensitizes tumor cells to CD94/NKG2A-positive NK cells.
J. Immunol. 2011 Oct;187(7):3546-54
Improved survival after allogeneic hematopoietic stem cell transplantation in recent years. A single-center study.
Biol. Blood Marrow Transplant. 2011 Nov;17(11):1688-97
NKG2D performs two functions in invariant NKT cells: direct TCR-independent activation of NK-like cytolysis and co-stimulation of activation by CD1d.
Eur. J. Immunol. 2011 Jul;41(7):1913-23
Rapid expansion and long-term persistence of elevated NK cell numbers in humans infected with hantavirus.
J. Exp. Med. 2011 Jan;208(1):13-21
Interactions of NK cell receptor KIR3DL1*004 with chaperones and conformation-specific antibody reveal a functional folded state as well as predominant intracellular retention.
J. Immunol. 2011 Jan;186(1):62-72
Reduced DNAM-1 expression on bone marrow NK cells associated with impaired killing of CD34+ blasts in myelodysplastic syndrome.
Leukemia 2010 Sep;24(9):1607-16
Distinct infiltration of neutrophils in lesion shoulders in ApoE-/- mice.
Am. J. Pathol. 2010 Jul;177(1):493-500
Identification of a novel KIR3DL1*072 allele by sequence-based typing.
Tissue Antigens 2010 Jul;76(1):74-5
Education of human natural killer cells by activating killer cell immunoglobulin-like receptors.
Blood 2010 Feb;115(6):1166-74
NK cells expressing inhibitory KIR for non-self-ligands remain tolerant in HLA-matched sibling stem cell transplantation.
Blood 2010 Apr;115(13):2686-94
Primary human tumor cells expressing CD155 impair tumor targeting by down-regulating DNAM-1 on NK cells.
J. Immunol. 2009 Oct;183(8):4921-30
KIR acquisition probabilities are independent of self-HLA class I ligands and increase with cellular KIR expression.
Blood 2009 Jul;114(1):95-104
Elevated numbers of Fc gamma RIIIA+ (CD16+) effector CD8 T cells with NK cell-like function in chronic hepatitis C virus infection.
J. Immunol. 2008 Sep;181(6):4219-28
Estimation of the size of the alloreactive NK cell repertoire: studies in individuals homozygous for the group A KIR haplotype.
J. Immunol. 2008 Nov;181(9):6010-9
Application of nine-color flow cytometry for detailed studies of the phenotypic complexity and functional heterogeneity of human lymphocyte subsets.
J. Immunol. Methods 2008 Jan;330(1-2):64-74
IFN-gamma production dominates the early human natural killer cell response to Coxsackievirus infection.
Cell. Microbiol. 2008 Feb;10(2):426-36
The CD16- CD56(bright) NK cell subset is resistant to reactive oxygen species produced by activated granulocytes and has higher antioxidative capacity than the CD16+ CD56(dim) subset.
J. Immunol. 2007 Oct;179(7):4513-9
A short-term dietary supplementation with high doses of vitamin E increases NK cell cytolytic activity in advanced colorectal cancer patients.
Cancer Immunol. Immunother. 2007 Jul;56(7):973-84
DNAX accessory molecule-1 mediated recognition of freshly isolated ovarian carcinoma by resting natural killer cells.
Cancer Res. 2007 Feb;67(3):1317-25
We always want to get in touch with highly motivated students and potential post-docs. If you are interested in doing research within our group please contact the group leader Kalle Malmberg.