Ingemar Ernberg Group

Our primary research interest is infection and cancer in humans.  We particularly study Epstein-Barr Virus (EBV)-infection, which can also be used as a model to study early steps in in vitro transformation, viral genetic switches, non-genetic variation and cancer cell metabolism.

Project Leaders in the Ingemar Ernberg Group


Barbro Ehlin-Henriksson Project

Elena Kashuba Project

LiFu Hu Project

Roland Möllby Project

Vladimir Kashuba Project

Research Summary

Our primary research interest is infection and cancer in humans.  We particularly study Epstein-Barr Virus (EBV)-infection, which can also be used as a model to study early steps in in vitro transformation, viral genetic switches, non-genetic variation and cancer cell metabolism.

Why is EBV of great biomedical interest today?

EBV is the most common virus in the human population (>90% of adults carry the virus) which normally gives rise to an inconspicuous or benign infection, paradoxically, however, under rare circumstances it induces tumors. It is associated with ten different forms of cancer in humans out of which some epithelial ones are very common in certain regions, in particular nasopharyngeal carcinoma (NPC) and gastric cancer (5-10 % thereof). Furthermore, it is the 4th largest infectious cause of cancer in humans involved in approximately 200,000 new cases of cancer every year worldwide.

This virus also offers one of the most complete models for studying tumorigenesis in man, from molecule to patient, exploiting the viral infection of human B-lymphocytes. The foundations for multistep tumorigenesis in this biology can be partly explored in vivo in patient cohorts where the tumor development increases significantly, due to immunosuppression like in post-transplant patients and HIV-carriers. The EBV cell line models allow comparison of non-malignant versus malignant phenotypes of human cancer in vitro (lymphoblastoid cell lines, LCL vs Burkitt´s lymphoma cell line, BL). We are using this virus to study the initiating immortalizing process and switches between resting and proliferating phenotypes to better understand EBV protein – host cell interactions involved in tumorigenesis controlling the switch from cell arrest to proliferation and reprogramming of metabolism.

Leading the Personalized Cancer Medicine (PCM)

We are also leading the Personalized Cancer Medicine (PCM) at Karolinska Institutet, funded by Radiumhemmets´ Research Funds, with the aim to establish and develop PCM as a leading treatment concept in academic cancer healthcare in Stockholm. PCM is an interdisciplinary research field and the main focus is to strengthen the infrastructure for local, national and international team science addressing PCM. Some 30 colleagues are affiliated with us to the PCM program, out of which half are part-time employed.

 

Group Members

Former group members and PhD students

Anna Aleman
Jenny Almqvist
Ender Altiok
Anna Birgersdotter
Carl-Ivar Brändén
Henrik Brändén
Rozina Caridha
Joakim Cöster
Sun Di
Ziming Du
Anneka Ehrnst
Kerstin Falk
Anna Friis
Fu Chen
Anneka Ehrnst
Jan Willem Gratama
Elvira Grigorieva
Sven Grützmeier
Lars  Holmgren
Qin Li
Uno Lindberg
Su Ling
Janos Minarovits
Ngyen van Do
Li-Sophie Rathje
Rickard Sandberg
JianYong Shao
Boris Troyanovsky
Maria Werner
Anita Westman
Gösta Winberg
Liang Wu
Xiangning Zhang
Xiaoying Zhou

Publications

Body mass index, body shape, and risk of nasopharyngeal carcinoma: A population-based case-control study in Southern China.
Feng R, Chang ET, Liu Z, Liu Q, Cai Y, Zhang Z, et al
Cancer Med 2019 04;8(4):1835-1844

Education aimed at increasing international collaboration and decreasing inequalities.
Ernberg I
Mol Oncol 2019 03;13(3):648-652

Reproductive history and risk of nasopharyngeal carcinoma: A population-based case-control study in southern China.
Feng RM, Chang ET, Liu Z, Liu Q, Cai Y, Zhang Z, et al
Oral Oncol. 2019 01;88():102-108

Cancer Core Europe: A European cancer research alliance realizing a research infrastructure with critical mass and programmatic approach to cure cancer in the 21st century.
Calvo F, Apolone G, Baumann M, Caldas C, Celis JE, de Lorenzo F, et al
Eur. J. Cancer 2018 11;103():155-159

Prediction of improved survival in patients with pancreatic cancer via IL-21 enhanced detection of mesothelin epitope-reactive T-cell responses.
Meng Q, Valentini D, Rao M, Liu Z, Xie S, Morgell A, et al
Oncotarget 2018 Apr;9(32):22451-22459

Medical History, Medication Use, and Risk of Nasopharyngeal Carcinoma.
Xiao X, Zhang Z, Chang ET, Liu Z, Liu Q, Cai Y, et al
Am. J. Epidemiol. 2018 10;187(10):2117-2125

Cytomegalovirus-Specific CD8+ T-Cells With Different T-Cell Receptor Affinities Segregate T-Cell Phenotypes and Correlate With Chronic Graft-Versus-Host Disease in Patients Post-Hematopoietic Stem Cell Transplantation.
Poiret T, Axelsson-Robertson R, Remberger M, Luo XH, Rao M, Nagchowdhury A, et al
Front Immunol 2018 ;9():760

Development of a population-based cancer case-control study in southern china.
Ye W, Chang ET, Liu Z, Liu Q, Cai Y, Zhang Z, et al
Oncotarget 2017 Oct;8(50):87073-87085

Ancient permafrost staphylococci carry antibiotic resistance genes.
Kashuba E, Dmitriev AA, Kamal SM, Melefors O, Griva G, Römling U, et al
Microb. Ecol. Health Dis. 2017 ;28(1):1345574

Degradation of cofilin is regulated by Cbl, AIP4 and Syk resulting in increased migration of LMP2A positive nasopharyngeal carcinoma cells.
Gainullin MR, Zhukov IY, Zhou X, Mo Y, Astakhova L, Ernberg I, et al
Sci Rep 2017 08;7(1):9012

Epstein-Barr virus (EBV) provides survival factors to EBV+ diffuse large B-cell lymphoma (DLBCL) lines and modulates cytokine induced specific chemotaxis in EBV+  DLBCL.
Wu L, Ehlin-Henriksson B, Zhou X, Zhu H, Ernberg I, Kis LL, et al
Immunology 2017 12;152(4):562-573

Epstein-Barr virus-encoded LMP2A stimulates migration of nasopharyngeal carcinoma cells via the EGFR/Ca2+/calpain/ITGβ4 axis.
Liang J, Zheng S, Xiao X, Wei J, Zhang Z, Ernberg I, et al
Biol Open 2017 Jun;6(6):914-922

Quantification of familial risk of nasopharyngeal carcinoma in a high-incidence area.
Liu Z, Chang ET, Liu Q, Cai Y, Zhang Z, Chen G, et al
Cancer 2017 Jul;123(14):2716-2725

George Klein (1925-2016).
Ernberg I, Kärre K, Wigzell H
Nature 2017 02;542(7641):296

Tumor suppressor BLU promotes TRAIL-induced apoptosis by downregulating NF-κB signaling in nasopharyngeal carcinoma.
Zhou J, Huang Z, Wang Z, Liu S, Grandien A, Ernberg I, et al
Oncotarget 2017 Jul;8(27):43853-43865

Fulminant anaplastic large cell lymphoma (ALCL) concomitant with primary cytomegalovirus (CMV) infection, and human herpes virus 8 (HHV-8) infection together with Epstein-Barr-virus (EBV) reactivation in a patient with asymptomatic HIV-infection.
Grützmeier S, Porwit A, Schmitt C, Sandström E, Åkerlund B, Ernberg I
Infect. Agents Cancer 2016 ;11():46

Short Chain Fatty Acids (SCFA) Reprogram Gene Expression in Human Malignant Epithelial and Lymphoid Cells.
Astakhova L, Ngara M, Babich O, Prosekov A, Asyakina L, Dyshlyuk L, et al
PLoS ONE 2016 ;11(7):e0154102

Oral Hygiene and Risk of Nasopharyngeal Carcinoma-A Population-Based Case-Control Study in China.
Liu Z, Chang ET, Liu Q, Cai Y, Zhang Z, Chen G, et al
Cancer Epidemiol. Biomarkers Prev. 2016 08;25(8):1201-7

A new prognostic histopathologic classification of nasopharyngeal carcinoma.
Wang HY, Chang YL, To KF, Hwang JS, Mai HQ, Feng YF, et al
Chin J Cancer 2016 May;35():41

Both high and low levels of cellular Epstein-Barr virus DNA in blood identify failure after hematologic stem cell transplantation in conjunction with acute GVHD and type of conditioning.
Li Q, Rane L, Poiret T, Zou J, Magalhaes I, Ahmed R, et al
Oncotarget 2016 May;7(21):30230-40

Dynamics inside the cancer cell attractor reveal cell heterogeneity, limits of stability, and escape.
Li Q, Wennborg A, Aurell E, Dekel E, Zou JZ, Xu Y, et al
Proc. Natl. Acad. Sci. U.S.A. 2016 Mar;113(10):2672-7

From the first curative targeted cancer treatment to the implementation of the most extensive healthcare reform.
Ernberg I
J. Intern. Med. 2015 Dec;278(6):643-4

Epigenetic downregulation of the ISG15-conjugating enzyme UbcH8 impairs lipolysis and correlates with poor prognosis in nasopharyngeal carcinoma.
Zhou X, Wei J, Chen F, Xiao X, Huang T, He Q, et al
Oncotarget 2015 Dec;6(38):41077-91

Proteoglycan expression correlates with the phenotype of malignant and non-malignant EBV-positive B-cell lines.
Tsidulko AY, Matskova L, Astakhova LA, Ernberg I, Grigorieva EV
Oncotarget 2015 Dec;6(41):43529-39

Integrin α9 gene promoter is hypermethylated and downregulated in nasopharyngeal carcinoma.
Nawaz I, Hu LF, Du ZM, Moumad K, Ignatyev I, Pavlova TV, et al
Oncotarget 2015 Oct;6(31):31493-507

Detection of nasopharyngeal carcinoma in Morocco (North Africa) using a multiplex methylation-specific PCR biomarker assay.
Nawaz I, Moumad K, Martorelli D, Ennaji MM, Zhou X, Zhang Z, et al
Clin Epigenetics 2015 ;7():89

SYK interaction with ITGβ4 suppressed by Epstein-Barr virus LMP2A modulates migration and invasion of nasopharyngeal carcinoma cells.
Zhou X, Matskova L, Rathje LS, Xiao X, Gish G, Werner M, et al
Oncogene 2015 Aug;34(34):4491-9

TCR+CD4-CD8- T cells in antigen-specific MHC class I-restricted T-cell responses after allogeneic hematopoietic stem cell transplantation.
Ahmed RK, Poiret T, Ambati A, Rane L, Remberger M, Omazic B, et al
J. Immunother. 2014 Oct;37(8):416-25

Development of a multiplex methylation specific PCR suitable for (early) detection of non-small cell lung cancer.
Nawaz I, Qiu X, Wu H, Li Y, Fan Y, Hu LF, et al
Epigenetics 2014 Aug;9(8):1138-48

Transcriptional Activity of Heparan Sulfate Biosynthetic Machinery is Specifically Impaired in Benign Prostate Hyperplasia and Prostate Cancer.
Suhovskih AV, Tsidulko AY, Kutsenko OS, Kovner AV, Aidagulova SV, Ernberg I, et al
Front Oncol 2014 ;4():79

Epstein Barr virus DNA analysis in blood predicts disease progression in a rare case of plasmablastic lymphoma with effusion.
Friis A, Akerlund B, Christensson B, Gyllensten K, Aleman A, Zou JZ, et al
Infect. Agents Cancer 2013 Jul;8(1):28

Increase of faecal tryptic activity relates to changes in the intestinal microbiome: analysis of Crohn's disease with a multidisciplinary platform.
Midtvedt T, Zabarovsky E, Norin E, Bark J, Gizatullin R, Kashuba V, et al
PLoS ONE 2013 ;8(6):e66074

An update on viral association of human cancers.
Zhang X, Zhang Z, Zheng B, He Z, Winberg G, Ernberg I
Arch. Virol. 2013 Jul;158(7):1433-43

EBV counteracts IL-21-induced apoptosis in an EBV-positive diffuse large B-cell lymphoma cell line.
Wu L, Ehlin-Henriksson B, Zhu H, Ernberg I, Klein G
Int. J. Cancer 2013 Aug;133(3):766-70

Development of a non-invasive method, multiplex methylation specific PCR (MMSP), for early diagnosis of nasopharyngeal carcinoma.
Zhang Z, Sun D, Hutajulu SH, Nawaz I, Nguyen Van D, Huang G, et al
PLoS ONE 2012 ;7(11):e45908

Epstein-Barr virus genome load is increased by therapeutic vaccination in HIV-l carriers, and further enhanced in patients with a history of symptomatic primary infection.
Friis AM, Akerlund B, Gyllensten K, Aleman A, Bratt G, Sandström E, et al
Vaccine 2012 Sep;30(42):6093-8

The TCF4/β-catenin pathway and chromatin structure cooperate to regulate D-glucuronyl C5-epimerase expression in breast cancer.
Mostovich LA, Prudnikova TY, Kondratov AG, Gubanova NV, Kharchenko OA, Kutsenko OS, et al
Epigenetics 2012 Aug;7(8):930-9

Genetic and epigenetic analysis of non-small cell lung cancer with NotI-microarrays.
Dmitriev AA, Kashuba VI, Haraldson K, Senchenko VN, Pavlova TV, Kudryavtseva AV, et al
Epigenetics 2012 May;7(5):502-13

Clinical significance of elevated spleen tyrosine kinase expression in nasopharyngeal carcinoma.
Du ZM, Kou CW, Wang HY, Huang MY, Liao DZ, Hu CF, et al
Head Neck 2012 Oct;34(10):1456-64

Host-Epstein-Barr virus relationship affected by immunostimulation in HIV-infected patients representing distinct progressor profile groups.
Friis AM, Åkerlund B, Gyllensten K, Aleman A, Ernberg I
Scand. J. Infect. Dis. 2012 May;44(5):388-92

Eight-signature classifier for prediction of nasopharyngeal [corrected] carcinoma survival.
Wang HY, Sun BY, Zhu ZH, Chang ET, To KF, Hwang JS, et al
J. Clin. Oncol. 2011 Dec;29(34):4516-25

CDH4 as a novel putative tumor suppressor gene epigenetically silenced by promoter hypermethylation in nasopharyngeal carcinoma.
Du C, Huang T, Sun D, Mo Y, Feng H, Zhou X, et al
Cancer Lett. 2011 Oct;309(1):54-61

A single nucleotide polymorphism in the matrix metalloproteinase 2 promoter is closely associated with high risk of nasopharyngeal carcinoma in Cantonese from southern China.
Shao JY, Cao Y, Miao XP, Huang MY, Deng L, Hao JJ, et al
Chin J Cancer 2011 Sep;30(9):620-6

Systems medicine and integrated care to combat chronic noncommunicable diseases.
Bousquet J, Anto JM, Sterk PJ, Adcock IM, Chung KF, Roca J, et al
Genome Med 2011 Jul;3(7):43

Upregulation of MiR-155 in nasopharyngeal carcinoma is partly driven by LMP1 and LMP2A and downregulates a negative prognostic marker JMJD1A.
Du ZM, Hu LF, Wang HY, Yan LX, Zeng YX, Shao JY, et al
PLoS ONE 2011 Apr;6(4):e19137

CDH4 as a novel putative tumor suppressor gene epigenetically silenced by promoter hypermethylation in nasopharyngeal carcinoma.
Du C, Huang T, Sun D, Mo Y, Feng H, Zhou X, et al
Cancer Lett. 2011 Oct;309(1):54-61

[Probiotics--friends or enemies of the intestine?].
Benno P, Ernberg I, Midtvedt T, Norin E, Zachrisson K
Lakartidningen ;107(13-14):907-9

[Intestinal flora--the biggest organ of the body. Unstable ecosystem which can easily topple].
Benno P, Blomquist L, Ernberg I, Midtvedt T, Möllby R, Norin E
Lakartidningen ;107(13-14):900-3

Inhibition spectrum studies of microthecin and other anhydrofructose derivatives using selected strains of Gram-positive and -negative bacteria, yeasts and moulds, and investigation of the cytotoxicity of microthecin to malignant blood cell lines.
Fiskesund R, Thomas LV, Schobert M, Ernberg I, Lundt I, Yu S
J. Appl. Microbiol. 2009 Feb;106(2):624-33

High mutability of the tumor suppressor genes RASSF1 and RBSP3 (CTDSPL) in cancer.
Kashuba VI, Pavlova TV, Grigorieva EV, Kutsenko A, Yenamandra SP, Li J, et al
PLoS ONE 2009 May;4(5):e5231

A review of human carcinogens--Part B: biological agents.
Bouvard V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, et al
Lancet Oncol. 2009 Apr;10(4):321-2

Infectious agents and lymphoma development: molecular and clinical aspects.
Ferreri AJ, Ernberg I, Copie-Bergman C
J. Intern. Med. 2009 Apr;265(4):421-38

Inflammation and tissue repair markers distinguish the nodular sclerosis and mixed cellularity subtypes of classical Hodgkin's lymphoma.
Birgersdotter A, Baumforth KR, Porwit A, Sjöberg J, Wei W, Björkholm M, et al
Br. J. Cancer 2009 Oct;101(8):1393-401

Cancer attractors: a systems view of tumors from a gene network dynamics and developmental perspective.
Huang S, Ernberg I, Kauffman S
Semin. Cell Dev. Biol. 2009 Sep;20(7):869-76

Connective tissue growth factor is expressed in malignant cells of Hodgkin lymphoma but not in other mature B-cell lymphomas.
Birgersdotter A, Baumforth KR, Wei W, Murray PG, Sjöberg J, Björkholm M, et al
Am. J. Clin. Pathol. 2010 Feb;133(2):271-80

Earlier Publications

Publications 2007-2008

Publications 1997-2000

Book release

Ingmar Ernberg, co-editor
Kvantfysiken och livet, 2020.
 

Ernberg, I. Et al.
Vad är liv, i kosmos, i cellen i människan?
Karolinska Universitet
y Press, Stockholm, 2010.

Contact

Ingemar Ernberg

Professor
C1 Department of Microbiology, Tumor and Cell Biology