Georg Klein Group

Our current activities have grown out from the work at the former Department of Tumor Biology that I have headed from 1957 to 1993. Currently active projects are concerned with Epstein Barr virus (EBV), oncogenes, and tumor suppressor genes (see projects section link above)

The group includes these project leaders:

Elena Kashuba Project Group

Barbro Ehlin-Henriksson website

Projects

George Kleins current activities also include the following problem areas:

Ad.1

In a recent paper Klein G. Cancer, apoptosis, and nonimmune surveillance, Cell Death and Differentiation, in press, I have briefly summarized this field as follows:

All organisms have powerful surveillance mechanisms that prevent the outgrowth of potentially cancerous cells. Many of them are highly conserved by evolution.

Believed for a long time as the most important safeguard,  immunological surveillance   now occupies a relatively minor place. It is still a powerful restraint against the outgrowth of virally transformed cells, however. This is the reason why tumorigenesis by Epstein-Barr virus, the papillomaviruses, and HHV-8, the Kaposi sarcoma herpesvirus, is either restricted to or more pronounced in the immunodefectives.

Non-immune surveillance is of four different kinds:

i).  Genetic surveillance   is largely based on DNA repair. It is the first line of defense, robustly built on a multitude of repair mechanisms. Defects in repair enzymes lead to specific cancer syndromes, several om them associated with multicancer families.

ii). The evidence for  epigenetic surveillance   is not yet firmly established. Preliminary evidence indicates the existence of inherited differences in the stringency of imprinting, possibly related to cancer risk.

iii).  Intracellular surveillance   prevents the outgrowth of cells driven by illegitimately activated oncogenes. Growth arrest and apoptosis are its two main arms. They are related but distinct. Growth arrest can be assigned to specific tumor suppressor genes, some of which are also linked to apoptotic pathways. Apoptosis is a firmly built multipathway system, as tightly controlled as cell division. Tumor development includes impairment or damage to one or several apoptotic pathways. Tumor cells use multiple escapes from apoptosis, including both the debilitation of proapoptotic pathways (e.g. p53) and activation of antiapoptotic mechanisms e.g. AKT/PI3K. Nevertheless, no tumor cell is completely resistant to apoptosis. Genotoxic agents such as irradiation or chemotherapy, act by inducing apoptosis in relatively apoptosis resistant cells.

Many therapeutic approaches, including clinical trials, aim at the reactivation of apoptosis. Partial of full restoration of a pathway that has been damaged in a given tumor cells is most likely to succeed. The Achilles heel approach involves mRNA or protein targeting, to reduce abnormally high enzyme levels and/or amplified oncoproteins.

iv).  Intercellular surveillance   is less well explored. It is clear, however, that loss of contact by epithelial cells leads to anoikis, a special form of apoptosis. Inhibition of tumor growth by adjacent normal cells is another phenomenon of great interest, largely unexplored by molecular methods. It may explain long range dormancy and counteract the outgrowth of disseminated tumor cells.

Ad.2

Our analytical work in this area focuses on antiapoptotic sculpting. Burkitt lymphoma (BL) has been one of our favorite tools for study during more than three decades. We were among the first to discover the viral (EBV) association of the high endemic African form, the crucial role of the Ig/myc translocation, the nature of the immune response against the tumor and some components of its relative resistance to apoptosis.

As a tumor driven by the myc oncogene the BL cell must acquire a relative resistance to apoptosis during its initial development. Several genetic and epigenetic changes were detected that contribute to this already in the in vivo tumor and in derived lines. The p53 pathway is crippled by either p53 mutation, ARF deletion or MDM2 amplification. The Rb pathway is usually impaired by p16 methylation. Nevertheless, the classical histology of the tumor  referred to as the 'starry sky' appearance  attests to ongoing apoptosis. The white 'stars' are macrophages containing remnants of apoptotic nuclei, derived from the lymphoma cells. Moreover, the tumor is exquisitely sensitive to chemotherapy that acts largely, if not entirely, through the induction of apoptosis.

These and many other findings show that apoptosis resistance is relative rather than absolute. Complete resistance is probably never achieved.

Our own work on BL relates to this problem in several ways. It intersects with a question we have pursued since we and others first showed that 98% of the high endemic (African) BLs carried the virus. In contrast to transformed normal B cells (immunoblasts) that carry the virus in vitro and also the immuneblastomas that arise in immunodefective persons, where the virus expresses its full growth transformation program that includes proliferation driving and antiapoptotic virus-cell interactions, BL cells do not express the growth transformation program. They only express one viral protein, EBNA1, required for the maintenance of the viral genomes in the free episomal form, and two small double stranded RNA molecules, the EBERs.

Cell growth is driven by the constitutively activated myc gene, apoptotic pathways are impaired, as already mentioned, in contrast to EBV transformed immunoblasts where they are not found. But what is, then, the role of EBV in BL?

As mentioned, Csaba Kiss and Laszlo Szekely have discovered that loss of EBV from three different BL lines is accompanied by the downregulation of the tcl-1 oncogene that can be reactivated again by EBV infection. tcl-1 is a powerful activator of the AKT pathway which is, in turn, a major antiapoptotic force. It is therefore likely that EBV contributes to the genesis of BL by conveying additional mechanisms of apoptosis resistance on the myc-driven BL cell.

it may also be noted that the Ig/myc translocation that occurs as an accident during physiological Ig-rearrangement pushes the cells towards an apoptotic or proliferative pathway at a point where they would be normally programmed to go to the resting state and turn into a long lived memory cell, or a plasma cell. It is therefore understandable that the main Ig/myc translocation carrying tumors, human BL, as well as mouse and rat plasmacytoma, depart from exactly these stages in the B cell life cycle. For the human BL cell, it has to be added that the long lived memory B cell is the site of latently persisting EBV. We have shown that the latently infected cells express the same minimalistic EBV program as the BL cells. The postulated apoptosis protection by latent EBV may thus act at a crucial point of apoptotic rescue, and thereby tip the balance towards proliferation.

Ad.3

Ever since the early 50s, my and my collaborators research work has revolved around multistep carcinogenesis. In the early 50s, we have been among the first to document the role of Darwinian variation and selection in the evolution of tumor cell populations. The ability of originally solid tumor cells to grow in the free suspension form of ascites tumors and the development of resistance against cytostatic drugs were the first phenotypic markers we studied in this context. Later we showed with Henry Harris in Oxford, that normal cells could suppress the tumorigenicity of even highly malignant partners in somatic hybrids derived by cell fusion. The suppressor genes, or, as we prefer to call them nowadays, the tumor antagonizing genes that were responsible for these effects could be localized to specific chromosomes.

An unusual feature of these somatic hybrid experiments was the identification of genetic components that suppressed in vivo tumorigenicity, but not in vitro growth

The work of several groups, including our own, pointed to the short arm of human

chromosome 3 (3p) as an important site of tumor antagonizing genes. Two different groups

pursue this area: Stefan Imreh and the group of Eugene Zabarovsky with which we still

collaborate. The more cytogenetic and more molecular approaches of the two groups are

mutually complementary. Recently, Stefan Imreh, Eugene Zabarovsky and I wrote a joint

review of this work ( Imreh, S., Klein, G., Zabarovsky, E.R. Search for unknown tumor

antagonizing genes. Genes, Chromosomes and Cancer, in press.).

The following conclusions are conceptually important:

We have set out to find one or a few crucial tumor suppressor loci on human 3p. Instead, we have identified several genes with proven or suspected tumor antagonizing activity. Over the relatively short 13.5 Mb strech of 3p21.3 more than 60 genes have been identified in four subregions. 29 among them are interesting tumor inhibitory candidates. Taken together with the large number of deletions and heterozygosis losses in tumor karyotypes, our findings suggest that the number of genes that can protect the organism against tumor development may have been underestimated. A multifactorial system seems to be unfolding, reminiscent of other multigenic surveillance systems.

We now postulate that the known tumor suppressor and antiapoptotic genes may be merely 'skyskrapers' in a much vaster landscape. The control of tissue integrity is vitally important. Most vitally important mechanisms are polygenically controlled. While the best known suppressor genes influence the cell cycle and/or apoptosis at the level of the tumor cell precursor, multiple and as yet unknown genetic systems may safeguard tissue integrity. The existence of tumor antagonizing genes, detected in the earlier somatic hybrid studies, and in the present elimination test (see the home page of Stefan Imreh and of Anna Szeles) exemplify, as already indicated, that some genes may antagonize tumor growth in vivo, but not tumor cell growth in vitro. We have given such genes the provisional designation asymmetric tumor suppressor. At present, the list contains the following genes: LTF, L1MD1, HYAL1, HYAL2 and VHL. The inhibition of in vivo growth, without any effect on in vitro proliferation was also confirmed in the gene inactivation test of Eugen Zabarovsky et al. using tet inducible vectors.

Currently, we are looking for additional 'asymmetric suppressors'. We are also exploring the possible relationship of some of these genes to what I have termed 'intercellular surveillance' under Ad.1, section iv above.

We have proposed previously Klein, G. Are there uncharted regions of tumor suppressor genes? IUBMB Life, 2001, 51: 1-3) that genes of the latter type may work in one of the following ways:

i). They might inhibit the the vascularization of the graft;

ii). They may prompt the tumor cell to differentiate in the in vivo microenvironment, but not in vitro;

iii). They may create a more restrictive tissue microenvironment.

We are pursuing these alternatives in a variety of functional studies, partly in collaboration with other groups.

Cancer and microenvironmental control  could fibroblasts play part of a systemic control function against cancer?

A joint project between the groups of Laszlo Szekely and Georg Klein

Project Members

  • Laszlo Szekely
  • Georg Klein
  • Emilie Flaberg
  • Hayrettin Guven
  • Tanya Pavlova
  • Vladimir Kashuba
  • Andrey Savchenko
  • Kent Andersson

Project background

In view of the large number of genetic and epigenetic changes that can initiate and promote tumor development, cancer can be seen nevertheless as a relatively rare disease. Two of three people never develop clinically manifest cancer and even the majority of heavy smokers remain cancer free (Klein G et al 2007-2008). Many different types of genetic variation can influence the propensity for neoplastic transformation. They are known to influence DNA repair, cell cycle checkpoint control, epigenetic imprinting or apoptotic proneness. Much less is known about the mechanisms that govern the interaction between cancer cells and the microenvironment. The question whether there is any cancer relevant genetic variation in microenvironmental control of tumor development has not been studied systematically. Increasing evidence indicates that cancer development requires changes both in the pre-cancerous cells and in their microenvironment. In order to study one aspect of the microenvironmental control, we departed from observations made already in the 1960´s, that normal fibroblasts can inhibit the growth of admixed cancer cells (neighbour suppression).

Project description & Method

We have developed an automated microscopy and image analysis platform permitting the examination of live mixed cell cultures growing on 384-well plates, at the single cell level and over time (Flaberg et al 2008, Markasz et al 2006-2009). Using this high throughput microscopy and image analysis approach we study how normal primary fibroblasts from different individuals inhibit tumor cell proliferation. Until now we have looked at the effect of primary fibroblasts from more than 100 different patients on 6 tumor cell lines. We have found that the majority of the fibroblasts could inhibit tumor cell proliferation. We have shown differences between fibroblasts in their capacity of inhibition, both between different donors and between different sites of the body that the fibroblasts were harvested from. In conclusion we could se a stronger inhibitory effect from fibroblasts of pediatric origin and from fibroblasts of the skin compared to fibroblasts of internal adult origin. Summarizing the effect of individual fibroblasts on all 6 tumor cell lines allowed us to identify the most and least inhibiting fibroblast.

Aim

Our aim is to find out if such neighbour suppression by normal cells could be part of a systemic control in the body. Does it contribute to the dormancy of disseminated tumor cells? Could it, for example, explain why the same cancer predisposing mutation leads to tumor development in one individual but not in another? Does it show genetic variation? Or, just simply, why dont we all get cancer?

Clinical relevance

The possible clinical relevance of the inhibitory effect of fibroblasts is studied in two ongoing collaborations. In collaboration with surgeons at the Örebro university hospital (Sweden) we have received prostate and skin biopsies from 40 men diagnosed with the same type of prostatic cancer. Twenty of these men have a progressive development of cancer while the other half of the group has been diagnosed at least five years ago with a tumor that has since been quiescent. In the second collaboration, with the University of Island, we are receiving fibroblasts from patients carrying the BRC2A-mutation. The donors of the BRC2A-fibroblasts have either been diagnosed with cancer early in life or have lived to an age of at least 60 years without being diagnosed with cancer. We are now comparing the inhibitory effect of these groups of fibroblasts against our panel of six tumor cell lines. To find a correlation between a poor inhibiting fibroblast and a progressive tumor development or an early onset of cancer would open up possibilities to more effective diagnose and treatment of cancer patients.

Right now

We are now dedicated to understand the mechanisms that could be responsible for the inhibition. We are focusing on the identified pair of the most and least inhibiting fibroblasts. We have found differences between these two fibroblasts in how they grow, how they form a monolayer and in their expression of smooth-muscle-actin. The immediate plans are to study these fibroblasts in higher resolution using live cell confocal imaging, to compare their gene profiles and to perform a siRNA-library screen looking for siRNAs that could inhibit the inhibiting effect of our most inhibiting fibroblasts.

 References:

Confrontation of fibroblasts with cancer cells in vitro: gene network analysis of transcriptome changes and differential capacity to inhibit tumor growth.
Alexeyenko A, Alkasalias T, Pavlova T, Szekely L, Kashuba V, Rundqvist H, et al
J. Exp. Clin. Cancer Res. 2015 ;34(1):62

High-throughput live-cell imaging reveals differential inhibition of tumor cell proliferation by human fibroblasts.
Flaberg E, Markasz L, Petranyi G, Stuber G, Dicso F, Alchihabi N, et al
Int. J. Cancer 2011 Jun;128(12):2793-802

Why do we not all die of cancer at an early age?
Klein G, Imreh S, Zabarovsky E
Adv. Cancer Res. 2007 ;98():1-16

Toward a genetics of cancer resistance.
Klein G
Proc. Natl. Acad. Sci. U.S.A. 2009 Jan;106(3):859-63

Extended Field Laser Confocal Microscopy (EFLCM): combining automated Gigapixel image capture with in silico virtual microscopy.
Flaberg E, Sabelström P, Strandh C, Szekely L
BMC Med Imaging 2008 ;8():13

Cytotoxic drug sensitivity of Epstein-Barr virus transformed lymphoblastoid B-cells.
Markasz L, Stuber G, Flaberg E, Jernberg A, Eksborg S, Olah E, et al
BMC Cancer 2006 ;6():265

Effect of frequently used chemotherapeutic drugs on the cytotoxic activity of human natural killer cells.
Markasz L, Stuber G, Vanherberghen B, Flaberg E, Olah E, Carbone E, et al
Mol. Cancer Ther. 2007 Feb;6(2):644-54

Hodgkin-lymphoma-derived cells show high sensitivity to dactinomycin and paclitaxel.
Markasz L, Kis L, Stuber G, Flaberg E, Otvos R, Eksborg S, et al
Leuk. Lymphoma 2007 Sep;48(9):1835-45

Klein G, Dermant P
Tumor Resistance. Cancer - The Outlaw Cell, 3rd Edition
Richard E LaFond, Editor, American Chemical Society Publication, in press 2008.

Publications

Published more than 1280 papers in the fields of experimental cell research and cancer research.

Inhibition of tumor cell proliferation and motility by fibroblasts is both contact and soluble factor dependent.
Alkasalias T, Flaberg E, Kashuba V, Alexeyenko A, Pavlova T, Savchenko A, et al
Proc. Natl. Acad. Sci. U.S.A. 2014 Dec;111(48):17188-93

The MEC1 and MEC2 lines represent two CLL subclones in different stages of progression towards prolymphocytic leukemia.
Rasul E, Salamon D, Nagy N, Leveau B, Banati F, Szenthe K, et al
PLoS ONE 2014 ;9(8):e106008

Decreased decorin expression in the tumor microenvironment.
Bozoky B, Savchenko A, Guven H, Ponten F, Klein G, Szekely L
Cancer Med 2014 Jun;3(3):485-91

Evolutionary aspects of cancer resistance.
Klein G
Semin. Cancer Biol. 2014 Apr;25():10-4

T cells modulate Epstein-Barr virus latency phenotypes during infection of humanized mice.
Heuts F, Rottenberg M, Salamon D, Rasul E, Adori M, Klein G, et al
J. Virol. 2014 Mar;88(6):3235-45

Large-scale hypomethylated blocks associated with Epstein-Barr virus-induced B-cell immortalization.
Hansen K, Sabunciyan S, Langmead B, Nagy N, Curley R, Klein G, et al
Genome Res. 2014 Feb;24(2):177-84

Novel signatures of cancer-associated fibroblasts.
Bozóky B, Savchenko A, Csermely P, Korcsmáros T, Dúl Z, Pontén F, et al
Int. J. Cancer 2013 Jul;133(2):286-93

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

Novel signatures of cancer-associated fibroblasts.
Bozóky B, Savchenko A, Csermely P, Korcsmáros T, Dúl Z, Pontén F, et al
Int. J. Cancer 2013 Jul;133(2):286-93

p53 contributes to T cell homeostasis through the induction of pro-apoptotic SAP.
Madapura H, Salamon D, Wiman K, Lain S, Klein G, Klein E, et al
Cell Cycle 2012 Dec;11(24):4563-9

Simultaneous detection of the two main proliferation driving EBV encoded proteins, EBNA-2 and LMP-1 in single B cells.
Rasul A, Nagy N, Sohlberg E, Ádori M, Claesson H, Klein G, et al
J. Immunol. Methods 2012 Nov;385(1-2):60-70

Control of cyclooxygenase-2 expression and tumorigenesis by endogenous 5-methoxytryptophan.
Cheng H, Kuo C, Yan J, Chen H, Lin W, Wang K, et al
Proc. Natl. Acad. Sci. U.S.A. 2012 Aug;109(33):13231-6

Epstein-Barr virus immortalization of human B-cells leads to stabilization of hypoxia-induced factor 1 alpha, congruent with the Warburg effect.
Darekar S, Georgiou K, Yurchenko M, Yenamandra S, Chachami G, Simos G, et al
PLoS ONE 2012 ;7(7):e42072

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

The architecture of fibroblast monolayers of different origin differentially influences tumor cell growth.
Flaberg E, Guven H, Savchenko A, Pavlova T, Kashuba V, Szekely L, et al
Int. J. Cancer 2012 Nov;131(10):2274-83

Latency type-dependent modulation of Epstein-Barr virus-encoded latent membrane protein 1 expression by type I interferons in B cells.
Salamon D, Adori M, Ujvari D, Wu L, Kis L, Madapura H, et al
J. Virol. 2012 Apr;86(8):4701-7

Soluble factors produced by activated CD4+ T cells modulate EBV latency.
Nagy N, Adori M, Rasul A, Heuts F, Salamon D, Ujvári D, et al
Proc. Natl. Acad. Sci. U.S.A. 2012 Jan;109(5):1512-7

Stem cell gene expression in MRPS18-2-immortalized rat embryonic fibroblasts.
Yenamandra S, Darekar S, Kashuba V, Matskova L, Klein G, Kashuba E
Cell Death Dis 2012 ;3():e357

Type I interferons directly down-regulate BCL-6 in primary and transformed germinal center B cells: differential regulation in B cell lines derived from endemic or sporadic Burkitt's lymphoma.
Salamon D, Adori M, He M, Bönelt P, Severinson E, Kis L, et al
Cytokine 2012 Mar;57(3):360-71

Epstein-Barr virus-encoded EBNA-5 forms trimolecular protein complexes with MDM2 and p53 and inhibits the transactivating function of p53.
Kashuba E, Yurchenko M, Yenamandra S, Snopok B, Szekely L, Bercovich B, et al
Int. J. Cancer 2011 Feb;128(4):817-25

Epstein-Barr virus encoded EBNA-3 binds to vitamin D receptor and blocks activation of its target genes.
Yenamandra S, Hellman U, Kempkes B, Darekar S, Petermann S, Sculley T, et al
Cell. Mol. Life Sci. 2010 Dec;67(24):4249-56

STAT6 signaling pathway activated by the cytokines IL-4 and IL-13 induces expression of the Epstein-Barr virus-encoded protein LMP-1 in absence of EBNA-2: implications for the type II EBV latent gene expression in Hodgkin lymphoma.
Kis L, Gerasimcik N, Salamon D, Persson E, Nagy N, Klein G, et al
Blood 2011 Jan;117(1):165-74

High-throughput live-cell imaging reveals differential inhibition of tumor cell proliferation by human fibroblasts.
Flaberg E, Markasz L, Petranyi G, Stuber G, Dicso F, Alchihabi N, et al
Int. J. Cancer 2011 Jun;128(12):2793-802

Epstein-Barr virus encoded EBNA-3 binds to vitamin D receptor and blocks activation of its target genes.
Yenamandra S, Hellman U, Kempkes B, Darekar S, Petermann S, Sculley T, et al
Cell. Mol. Life Sci. 2010 Dec;67(24):4249-56

Interaction of Epstein-Barr virus (EBV) with human B-lymphocytes.
Klein G, Klein E, Kashuba E
Biochem. Biophys. Res. Commun. 2010 May;396(1):67-73

Chromosomal rearrangements after ex vivo Epstein-Barr virus (EBV) infection of human B cells.
Lacoste S, Wiechec E, Dos Santos Silva A, Guffei A, Williams G, Lowbeer M, et al
Oncogene 2010 Jan;29(4):503-15

IL-21 imposes a type II EBV gene expression on type III and type I B cells by the repression of C- and activation of LMP-1-promoter.
Kis L, Salamon D, Persson E, Nagy N, Scheeren F, Spits H, et al
Proc. Natl. Acad. Sci. U.S.A. 2010 Jan;107(2):872-7

2009

Burkitt lymphoma.
Klein E, Klein G
Semin. Cancer Biol. 2009 Dec;19(6):345-6

To the genesis of Burkitt lymphoma: regulation of apoptosis by EBNA-1 and SAP may determine the fate of Ig-myc translocation carrying B lymphocytes.
Nagy N, Klein G, Klein E
Semin. Cancer Biol. 2009 Dec;19(6):407-10

Comparative analysis of the Epstein-Barr virus encoded nuclear proteins of EBNA-3 family.
Yenamandra S, Sompallae R, Klein G, Kashuba E
Comput. Biol. Med. 2009 Nov;39(11):1036-42

The proapoptotic function of SAP provides a clue to the clinical picture of X-linked lymphoproliferative disease.
Nagy N, Matskova L, Kis L, Hellman U, Klein G, Klein E
Proc. Natl. Acad. Sci. U.S.A. 2009 Jul;106(29):11966-71

Burkitt lymphoma--a stalking horse for cancer research?
Klein G
Semin. Cancer Biol. 2009 Dec;19(6):347-50

Changes in chemokines and chemokine receptor expression on tonsillar B cells upon Epstein-Barr virus infection.
Ehlin-Henriksson B, Liang W, Cagigi A, Mowafi F, Klein G, Nilsson A
Immunology 2009 Aug;127(4):549-57

High mutability of the tumor suppressor genes RASSF1 and RBSP3 (CTDSPL) in cancer.
Kashuba V, Pavlova T, Grigorieva E, Kutsenko A, Yenamandra S, Li J, et al
PLoS ONE 2009 ;4(5):e5231

PRIMA-1MET induces nucleolar translocation of Epstein-Barr virus-encoded EBNA-5 protein.
Stuber G, Flaberg E, Petranyi G, Otvös R, Rökaeus N, Kashuba E, et al
Mol. Cancer 2009 ;8():23

Toward a genetics of cancer resistance.
Klein G
Proc. Natl. Acad. Sci. U.S.A. 2009 Jan;106(3):859-63

2008

Leukotriene B4 activates T cells that inhibit B-cell proliferation in EBV-infected cord blood-derived mononuclear cell cultures.
Liu A, Claesson H, Mahshid Y, Klein G, Klein E
Blood 2008 Mar;111(5):2693-703

EBV-encoded EBNA-6 binds and targets MRS18-2 to the nucleus, resulting in the disruption of pRb-E2F1 complexes.
Kashuba E, Yurchenko M, Yenamandra S, Snopok B, Isaguliants M, Szekely L, et al
Proc. Natl. Acad. Sci. U.S.A. 2008 Apr;105(14):5489-94

Segmental duplications and evolutionary plasticity at tumor chromosome break-prone regions.
Darai-Ramqvist E, Sandlund A, Müller S, Klein G, Imreh S, Kost-Alimova M
Genome Res. 2008 Mar;18(3):370-9

HYAL1 and HYAL2 inhibit tumour growth in vivo but not in vitro.
Wang F, Grigorieva E, Li J, Senchenko V, Pavlova T, Anedchenko E, et al
PLoS ONE 2008 ;3(8):e3031

 

All Publications 1995-2008

Selected Publications 1995-2008 (Pdf file, 84 Kb)

Selected Publications 1996-2006

Selected Publications 1996-2006 (Pdf file, 84 Kb)

Publications 1980-1995

Publications 1980-1995 (Pdf file, 266 Kb)

Publications 1951-1980

Publications 1951-1980 (Pdf file, 198 Kb)

Group Members

Professor emeritus

Georg Klein

Phone: 08-524 867 30
Organizational unit: George Klein group
E-mail: Georg.Klein@ki.se

Graduate Student

Twana Hasseb Abdulahad Alkasalias

Organizational unit: George Klein group
E-mail: twana.alkasalias@ki.se

Twana Hasseb Abdulahad AlkasaliasGraduate Student
Toni BiskupovicAssociated
Barbro Ehlin-HenrikssonCoordinator
Emilie FlabergAssociated
Emilie FlabergPostdoc
Hayrettin GuvenPostdoc
Irina HolodnukaAssociated
Stefan ImrehAssociated
Elena KashubaSenior researcher
Vladimir KashubaSenior lab manager
Eva KleinAssociated
Eva KleinProfessor emerita
Georg KleinProfessor emeritus
Klas LöwbeerAssociated
Maria LöwbeerBiomedical scientist
Yassine MaaroufAssociated
Muhammad MushtaqGraduate Student
Noemi NagyAssociated
Tatiana PavlovaPostdoc
Eahsan RasulAssociated
Eahsan RasulSenior researcher
Daniel SalamonAssociated
Andrii SavchenkoAssociated
Liang WuAssociated

  Laboratory assistant Kenth Andersson

Curriculum Vitae 

George Klein

Date of birth: July 28, 1925 in Budapest, Hungary.

M.D. Karolinska Institute, 1951.

D.Sc. (Hon.) University of Chicago, 1966.

M.D. (hon.) University of Debrecen, Hungary, 1988.

Ph.D. (h.c.) Hebrew University, Jerusalem, 1989.

D.Sc. (h.c.) University of Nebraska, 1991.

Ph.d.(h.c.) Tel Aviv University, 1994.

Honorary Doctor of Medical Science, Osaka University, 2001.

Instructor in histology, Budapest University, 1945;

Instructor in pathology, Budapest University, 1946;

Research Fellow, Karolinska Institutet, 1947-1949.

Assistant Professor of Cell Research 1951-1957.

Professor of Tumor Biology and Head of Department of Tumor Biology, Karolinska Institutet, 1957-1993,

Research Group Leader, Microbiology and Tumor Biology Center, Karolinska Institute since 1993.

Guest Investigator at the Institute for Cancer Research, Philadelphia, Pa., 1950:

Visiting Professor, Stanford University, 1961;

Fogarty Scholar, NIH, 1972;

Visiting Professor, Hebrew University, Hadassah Medical School, 1973-1993 .

Member of the Royal Swedish Academy of Sciences.

Foreign Member of the Finnish Scientific Society,

Foreign Associate of the National Academy of Sciences of the United States;

Honorary Member of the Hungarian Academy of Sciences;

Honorary Member of the American Association of Immunologists.

Foreign Member of the American Philosophical Society.

Honorary Member of the French Society of Immunology.

Honorary Foreign Member of the American Academy of Arts and Sciences.

Honorary Member of the American Association for Cancer Research.

Member of the Scientific Advisory Board of Ludwig Institute,

Editor, Advances in Cancer Research.

Member of the Nobel Assembly of Karolinska Institutet 1957-1993.

Titular member of the European Academy of Sciences, Arts and Humanities, 1999.

Academy of Cancer Immunology, 1999.

Honorary Fellowship of the European Association for Cancer Research, 2002.

Bertha Goldblatt Teplitz Award together with Eva Klein, 1960.

Dunham Lecturer of Harvard University, 1966.

Clowes Memorial Lecturer, American Association of Cancer Research, 1967.

Prize of the Danish Pathological Society, 1967.

Lennander Lecturer of the Swedish Medical Association, 1967.

Rabbi Shai Shacknai Prize in Tumor Immunology, 1972.

Bertner Award, 1973.

Annual Award of the American Cancer Society, 1973.

Harvey Lecturer, 1973.

Prix Griffuel, 1974.

Harvey Prize 1975.

Gardner Award, 1976.

Behring Prize, 1977.

Björken Prize, 1978.

Sloan Prize from the General Motors Cancer Research Foundation, 1979.

Award of the Santa Chiara Academy, Italy, 1979.

Erik Fernström Prize (with Eva Klein), 1983.

Anniversary Prize of the Swedish Medical Association, 1983.

Honorary Member of the American Association of Cancer Research.

The Letterstedt Prize of the Royal Swedish Academy of Sciences, 1989.

Dobloug Prize of the Swedish Academy of Literature, 1990.

Lisl and Leo Eitinger's Prize of Oslo University, 1990.

Donald Wae Waddel Lecturer, The University of Arizona, 1991.

Recipient of the Culture Prize of the Swedish publisher " Nature and Culture", 1995.

Dr Tovi Comel-Walerstein C.A.I.R Institute Science Award for 1995 (Bar-Ilan University, Israel), 1995.

Thomas P. Infusino Prize and Lectureship in Cancer Causation and Epidemiology, 1996 (together with Eva Klein).

Kaposi Award, 1996.

Chester Stock Award of Sloan Kettering Memorial Center, 1997.

Orden Nacional al Mérito de la República de Colombia, 1998.

Robert Koch gold medal 1998.

Institute of Human Virology, Lifetime Achievement Award, 1998.

Prize of the Brupbacher Foundation, Zürich, 1999.

Paracelsus medal 2001.

The Wick R. Williams Memorial Lecture Award, 2001.

Ingemar Hedenius Prize 2002.

G.J. Mendel honorary medal for merit in the biological sciences, 2005.

IARC medal of honour 2006.

Herbert J. Block Memorial Lectureship Award at the Ohio State University 2008.

Biomedicum medaljen, Helsinfors,Finland,2009,

KI:s Jubileumsmedalj 2010.

Royal Award of The Swedish Academy 2010

Distinguished Professor Award Karolinska Institute 2010

Published more than 1385 papers in the fields of experimental cell research and cancer research.

Published 13 essay books in Swedish, three of them were translated to English, individual translations to Finnish, Lituanian, Hungarian, Romanian, French, Czech and Faroese.

Memberships

Member of the Royal Swedish Academy of Sciences
    •    Foreign Member of the Finnish Scientific Society
    •    Foreign Associate of the National Academy of Sciences of the United States
    •    Honorary Member of the Hungarian Academy of Sciences
    •    Honorary Member of the American Association of Immunologists
    •    Foreign Member of the American Philosophical Society
    •    Honorary Member of the French Society of Immunology
    •    Honorary Foreign Member of the American Academy of Arts and Sciences.
    •    Honorary Member of the American Association for Cancer Research
    •    Member of the Scientific Advisory Board of Ludwig Institute
    •    Editor, Advances in Cancer Research
    •    Member of the Nobel Assembly of Karolinska Institutet 1957-1993
    •    Titular member of the European Academy of Sciences, Arts and Humanities, 1999, Academy of Cancer Immunology, 1999
    •    Honorary Fellowship of the European Association for Cancer Research, 2002
    •    G.J. Mendel honorary medal for merit in the biological sciences, 2005
    •    IARC medal of honour 2006.

Georg Klein's Awards

    •    Bertha Goldblatt Teplitz Award together with Eva Klein, 1960
    •    Dunham Lecturer of Harvard University, 1966
    •    Clowes Memorial Lecturer, American Association of Cancer Research, 1967
    •    Prize of the Danish Pathological Society, 1967
    •    Lennander Lecturer of the Swedish Medical Association, 1967
    •    Rabbi Shai Shacknai Prize in Tumor Immunology, 1972.
    •    Bertner Award, 1973
    •    Annual Award of the American Cancer Society, 1973
    •    Harvey Lecturer, 1973
    •    Prix Griffuel, 1974
    •    Harvey Prize 1975
    •    Gardner Award, 1976
    •    Behring Prize, 1977.
    •    Björken Prize, 1978.
    •    Sloan Prize from the General Motors Cancer Research Foundation, 1979
    •    Award of the Santa Chiara Academy, Italy, 1979
    •    Erik Fernström Prize (with Eva Klein), 1983
    •    Anniversary Prize of the Swedish Medical Association, 1983
    •    Honorary Member of the American Association of Cancer Research.
    •    The Letterstedt Prize of the Royal Swedish Academy of Sciences, 1989.
    •    Dobloug Prize of the Swedish Academy of Literature, 1990
    •    Lisl and Leo Eitinger's Prize of Oslo University, 1990.
    •    Donald Wae Waddel Lecturer, The University of Arizona, 1991
    •    Recipient of the Culture Prize of the Swedish publisher " Nature and Culture", 1995
    •    Dr Tovi Comel-Walerstein C.A.I.R Institute Science Award for 1995 (Bar-Ilan University, Israel), 1995.
    •    Thomas P. Infusino Prize and Lectureship in Cancer Causation and Epidemiology, 1996 (together with Eva Klein).
    •    Kaposi Award, 1996
    •    Chester Stock Award of Sloan Kettering Memorial Center, 1997
    •    Orden Nacional al Mérito de la República de Colombia, 1998.
    •    Robert Koch gold medal 1998.
    •    Institute of Human Virology, Lifetime Achievement Award, 1998
    •    Prize of the Brupbacher Foundation, Zürich, 1999
    •    Paracelsus medal 2001
    •    The Wick R. Williams Memorial Lecture Award, 2001
    •    Ingemar Hedenius Prize 2002.

Georg Klein's Books

Istället för Hemland, Bonniers, 1984.

Ateisten och den Heliga Staden, Bonniers, 1987.

Pietà, Bonniers, 1989.

Motståndet (med Per Ahlmark) Bonniers, 1991.

Utvägen, Bonniers 1992.

Hack i häl på Minerva (med Lars Gyllensten), Bonniers 1993.

Den Sjunde Djävulen, Bonniers, 1995.

Korpens blick, Bonniers, 1998.

Så jag kan svara döden, när den kommer, Bonniers, 2001.

Skapelsens fullkomlighet och livets tragik, Bonniers, 2005.

Péters Europa, Eva Dickson, Egon Fenyö, Georg Klein, Carlssons Bokförlag, 2005.

Meteorer, Bonniers, 2008.

Jag återvänder aldrig, Bonniers 2011.

nya tankar om kreativitet och flow! Brombergs 2012

The Atheist and the Holy City The MIT Press, 1990

Pietá MIT Press, 1992

Live Now Prometheus Books, 1997

Ravnens Blick Humanist forlag, 2003

Translations of selected essays in Finnish, French, Dutch, Czech, Romanian, Hungarian, Faeroese and Japanese

Tumour Biology