Department of Genetics, Microbiology Department of Genetics, Microbiology and Toxicology (GMT)and Toxicology (GMT)

Radiation BiologyRadiation Biology

Prof. Andrzej WojcikProf. Andrzej Wojcik

Prof. Mats Harms-RingdahlProf. Mats Harms-Ringdahl

ToxicologyToxicology

Prof. Thomas HelledayProf. Thomas Helleday

Prof. Ulf Rannug Prof. Ulf Rannug

Prof. Dag JenssenProf. Dag Jenssen

Centre for Radiation Centre for Radiation

Protection ResearchProtection Research

(CRPR)(CRPR)

Molecular Mechanisms Molecular Mechanisms

in Cancer in Cancer

/ Dag Jenssen, GMT

Radiation Biology (AW & MHR)

2 Profs2 Profs

11 Postdoc Postdoc

55 PhD students PhD students

22 Master students Master students

MMechanismechanisms of cellular and systemics of cellular and systemic

effects of exposure to ionising radiationeffects of exposure to ionising radiation

EU grantsEU grantsSwedish Radiation Safety AuthoritySwedish Radiation Safety Authority

Radiation Biology (AW & MHR)

Mechanisms Mechanisms of individual sensitivity toof individual sensitivity toionising radiation: ionising radiation:

• Differences in DNA-damage response pathways between Differences in DNA-damage response pathways between cohorts of patients with normal or severe healthy tissue cohorts of patients with normal or severe healthy tissue reactions to tumour therapy.reactions to tumour therapy.•Screening for polymorphisms in genes for DNA-repair, cell Screening for polymorphisms in genes for DNA-repair, cell cycle regulation and apotosiscycle regulation and apotosis

• Search for diagnostic tools to identify the persons at risk.Search for diagnostic tools to identify the persons at risk.

Patient with severe side-effect

following radiotherapy

Radiation Biology (AW & MHR)

What What areare the risk the riskss of radiation at low doses of radiation at low doses??

CaCann we improve biological dosimetry? we improve biological dosimetry?

New technologies will determine doses with high precision?New biomarkers for DNA-damage response pathways

Epidemiological data

(above background)

(excesscancers)

Is the dose response curve Is the dose response curve

non-linear?non-linear?

Identification of new responseIdentification of new response

pathways for very low doses.pathways for very low doses.

??

Professor Thomas Helleday’s group

SU groupSU group

1 Prof1 Prof

10 Postdocs & senior scientists10 Postdocs & senior scientists

8 PhD students8 PhD students

1 Master students1 Master students

DNA repair in cancer therapyDNA repair in cancer therapyMain grants from:Main grants from:

Swedish Scientific Research Council (VR)Swedish Scientific Research Council (VR)

Swedish Pain Relief Foundation (Smärtafonden)Swedish Pain Relief Foundation (Smärtafonden)

Swedish Cancer Foundation (Cancerfonden)Swedish Cancer Foundation (Cancerfonden)

Swedish Children’s Cancer Foundation (Barncancerfonden)Swedish Children’s Cancer Foundation (Barncancerfonden)

Oxford groupOxford group

6 Postdocs6 Postdocs

7 DPhil students7 DPhil students

Niklas Schultz, Helge Gad, Fredrik Johansson, Anne Lagerkvist,Niklas Schultz, Helge Gad, Fredrik Johansson, Anne Lagerkvist,

Linda Savolainen, Ingegerd Elvers, Cecilia Ström, Petra Groth, Linda Savolainen, Ingegerd Elvers, Cecilia Ström, Petra Groth,

Firas Al-Ubadi, Ivaylo Stoimenov, Kristian Grimberg, Guoli Liu, Firas Al-Ubadi, Ivaylo Stoimenov, Kristian Grimberg, Guoli Liu,

Muntasir MamunMuntasir Mamun

Research areasResearch areas• Stalling of Replication fork and Replication RestartStalling of Replication fork and Replication Restart• Homologous recombinationHomologous recombination• DNA replication terminationDNA replication termination• DNA repair in cancer (cells + clinical material)DNA repair in cancer (cells + clinical material)

SU - DNA Repair team

SU - Biochemistry/proteomicsAnn-Sofie Jemth, Olga LosevaAnn-Sofie Jemth, Olga Loseva

Research areasResearch areas• Poly (ADP ribose) polymerasesPoly (ADP ribose) polymerases• Proteomics after DNA damageProteomics after DNA damage• Purification of protein targets for cancer treatmentPurification of protein targets for cancer treatment

SU – Cancer BiologyTatjana Djureinovic, Evgenia GubanovaTatjana Djureinovic, Evgenia Gubanova

Research areasResearch areas• DNA damage signalling in cancerDNA damage signalling in cancer• Evaluation of targets for cancer treatmentEvaluation of targets for cancer treatment

SciLifeLab - High-Throughput Screening

Bo LundgrenBo Lundgren

Research areasResearch areas

• RNAi library screens in cellsRNAi library screens in cells

• Identify targets for cancer treatmentsIdentify targets for cancer treatments

• Map functional genetic networksMap functional genetic networks

SU – Medical Chemistry

Martin Scobie, Tobias KoolmeisterMartin Scobie, Tobias Koolmeister

Research areasResearch areas

• Lead optimisation - Parallell organic chemistry synthesisLead optimisation - Parallell organic chemistry synthesis

Professor Ulf Rannugs group

1 Prof1 Prof

1 Postdoc1 Postdoc

3 PhD students3 PhD students

1 Master student1 Master student

Natural non-persistent bioactive Natural non-persistent bioactive aryl hydrocarbon receptor ligands aryl hydrocarbon receptor ligands in humansin humans

The The Swedish research Council FORMASSwedish research Council FORMAS

Professor Ulf Rannug, cont.

NH

HN

O

CYP1

H2N CHC

CH2

OH

O

HNTrp N

H

HN

OOH

NH

HN

OOH

HO

AhRE

CHEMICAL INHIBITORS

AhRAhRNFNFĸĸBB

Formation and metabolism of

the suggested physiological

Ah receptor ligand 6-formyl-

indolo[3,2-b]carbazole (FICZ)

HPLC, LC/MS/MS

Recombinant human enzymes

Human cells in vitro

Human blood, plasma and urine samples

Professor Ulf Rannug, cont.

TRYPTOPHAN PROLIFERATION/APOPTOSIS

DEVELOPMENT

DIFFERENTIATION

HOMEOSTASIS

IMMUNE RESPONS

INFLAMMATION

NEUROENDOCRINE

FUNCTIONS

STRESS RESPONSES RESPONSES

Genomic and

non-genomic

regulationARYL HYDROCARBONRECEPTOR (AhR)

SECONDMESSENGERS

OTHER RECEPTORS (LXRR)

FICZActiveligand

oxFICZInactiveligand

CYP1 AOX

TRYPTAMINE

I-3-A

The new AhR paradigm

Professor Dag Jenssen’s group

2 Profs2 Profs

2 Postdocs2 Postdocs

2 PhD students2 PhD students

3 Master students3 Master students

Molecular/cellular mechanisms for induced Molecular/cellular mechanisms for induced mutationsmutations EU grantsEU grantsSwedish Cancer SocietySwedish Cancer SocietySwedish Radiation Protection AuthoritySwedish Radiation Protection Authority

/ Dag Jenssen, GMT

/ Dag Jenssen, GMT

Professor Dag Jenssen, cont.

Mechanisms involved in the repair of genomic Mechanisms involved in the repair of genomic DNA intra-strand cross-links (Cf, 2010-2013)DNA intra-strand cross-links (Cf, 2010-2013)

The basis for cancer risk assessment of lifestyle factorsThe basis for cancer risk assessment of lifestyle factors

Cell culture modelsCell culture modelsDNA repairDNA repair

DNA replicationDNA replication

Mutation assayMutation assay

DNA sequencingDNA sequencing

Professor Dag Jenssen, cont.

Molecular/cellular protection mechanisms against Molecular/cellular protection mechanisms against carcinogenic constituents in food (EU, 2010-2014)carcinogenic constituents in food (EU, 2010-2014)

The basis for developing Functional FoodsThe basis for developing Functional Foods

/ Dag Jenssen, GMT