Hans Einar Krokan
Bakgrunn og aktiviteter
Short CV
BIOGRAPHICAL SKETCH
NAME |
POSITION TITLE |
|||
Hans Einar Krokan |
Professor/Chairman |
|||
EDUCATION/TRAINING |
||||
INSTITUTION AND LOCATION |
DEGREE |
YEAR(s) |
FIELD OF STUDY |
|
|
M.D |
1970 |
Medicine |
|
|
Ph.D. |
1977 |
Biochemistry |
|
A. Positions and Honors
Positions and Employment
1970-1972 Internship, in surgery, internal medicine and community medicine
1972 Doctor in the air force (captain), Ørlandet military airport
1972-1977 Research fellow,
1977-1979 Post doctoral fellow (Fogarty International Fellowship),
1979-1985 Associate professor in biochemistry,
1983-1984 Visiting scientist, (Stipend from International Cancer Union, Eleanor Roosevelt Awardee), National Cancer Institute, Lab. Human Carcinogenesis,
1985-1988 Department head, Department of biotechnology, Norsk Hydro Research Centre Porsgrunn, from 1987 Director of Research, Biomedical Section (responsible for biotechnology, organic chemistry and preclinical- and clinical medicine)
1988-1993 Professor at
1993-present Professor in medicine/molecular Biology, Medicine,
1990-2002 Director/Chairman,
2006- Director/Chairman, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (formerly University of Trondheim)
2006- Norwegian delegate ESFRI (European Strategy Forum for Research Infrastructures) Biological and medical Road Map Working Group
Honors
1977-1979 Fogarty International Fellowship
1983 Eleanor Roosevelt Awardee
1994 Elected member of The Royal Norwegian Academy of Science and Letters
1997 Honorary member of the Norwegian Biochemical Society
2000 Elected member of the European Molecular Biology Organization (EMBO)
2004 Anders Jahre’s Award for Medical Research; “For his groundbreaking DNA research” (a prize given annually to one/two scientist(s) in the 5 Nordic countries).
2008 King Olav Vs Prize for Cancer Research
Research experience and interests:
Hans E. Krokan has established research groups within DNA replication, genome maintenance and DNA repair, omega-3 fatty acids research, and research on predisposition to lung cancer. He has also established extensive research programs in an industrial company (Norsk
B. Selected peer-reviewed publications (from approximately 150 scientific articles in international journals, mostly within DNA replication and DNA repair since 1975).
Krokan, H.E. and Wittwer, C. (1981) Uracil-DNA glycosylase: General properties substrate specificity and effect of uracil analogs. Nucleic Acids Res. vol. 5, 2599-2613.
Slupphaug, G., Olsen, L.C., Aasland, R., Helland, D.E. and Krokan, H.E. (1991). Cell cycle kinetics and hybrid arrest identifies a major uracil-DNA glycosylase. Nucl. Acids Res. 19, 5131-5137
Slupphaug, G., Markussen, F.H., Olsen, L.C., Aasland, R., Aarsæther, N., Bakke, O., Krokan, H.E. and Helland, D.E. and (1993). Nuclear and mitochondrial forms of human uracil-DNA glycosylase are encoded by the same gene. Nucl. Acids Res. 21, 2579-2584
Slupphaug, G., Eftedal, I., Kavli, B., Bharati, S., Helle, N., Haug, T., Levine, D.W. and Krokan, H.E. (1995) Properties of a Recombinant Human Uracil-DNA Glycosylase from the UNG-gene and Evidence that UNG Encodes the Major Uracil-DNA Glycosylase. Biochemistry 34, 128-138
Mol, C.D., Arvai, A.S., Slupphaug, G., Kavli, B., Alseth, I., Krokan, H.E. and Tainer, J.A. (1995) Crystal Structure and mutational analysis of Human Uracil-DNA glycosylase: Structural basis for specificity and catalysis. Cell 80, 869-878
Mol, C.D., Arvai, A.S., Sanderson, R.J., Slupphaug, G., Kavli, B., Krokan, H.E., Mosbaugh, D.W. and Tainer, J.A. (1995). Crystal Structure of Human Uracil-DNA Glycosylase in Complex with a Protein Inhibitor. Cell 82, 701-708
Kavli, B., Slupphaug, G., Mol, C.D., Arvai, A.S., Petersen, S.B., Tainer, J.A., and Krokan, H.E. (1996). Excision of cytosine and thymine from DNA by mutants of human uracil-DNA glycosylase. EMBO J. 15, 3442-3447
Slupphaug, G., Kavli, B., Mol, C.D., Arvai, A., Krokan, H.E. and Tainer, J.A. (1996). Structure of human uracil-DNA glycosylase bound to DNA shows a nucleotide flipping mechanism. Nature 384, 87-92
Nagelhus, T., Haug, T., Singh, K.K., Keshav, K.F., Skorpen, F., Bharati, S., Otterlei, M., Lindmo, T., Benichou, S., Benarous, R. and Krokan, H.E. (1997). A sequence in the N-terminal region of human uracil-DNA glycosylase with homology to XPA interacts with the C-terminal part of the 34 kDa subunit of replication protein A. J. Biol. Chem. 272, 6561-6566
Krokan, H.E., Standal, R. and Slupphaug,G (1997) DNA glycosylases in base excision repair. Biochem. J. 325, 1-16
Parikh, S.S., Mol, C.D., Slupphaug, G., Bharati, S., Krokan, H.E. and Tainer, J.A. (1998). Base excision repair initiation revealed by crystal structures and binding kinetics of human uracil-DNA glycosylase. EMBO J. 17, 5214-5226
Otterlei, M., Haug, T., Nagelhus, T.A., Slupphaug, G., Lindmo, T. and Krokan, H.E. (1998). Nuclear and mitochondrial splice forms of human uracil-DNA glycosylase contain a complex nuclear localization signal and a strong classical mitochondrial localizations signal, respectively. Nucl. Acids Res. 20, 4611-4617
Otterlei, M., Warbrick, E., Slupphaug, G., Nagelhus, T.A., Haug, T., Akbari, M., Aas, P.A., Steinsbekk, K., Bakke, O., and Krokan, H.E. (1999) Postreplicative Base Excision Repair in Replication Foci. EMBO J. 18, 3834-3844
Parikh, S., Walcher, G., Jones, G.D., Slupphaug, G., Krokan, H.E.,
Otterlei, M., Kavli, B., Standal, R., Skjelbred, C., Bharati, S., Krokan, H.E. (2000). Repair of chromosomal abasic sites in vivo involves at least three different repair pathways. EMBO J. 19, 5542-5551
Kavli, B., Sundheim, O., Akbari, M., Otterlei, M., Nilsen, H., Skorpen, F., Aas, P.A., Hagen, L., Krokan, H.E. and Slupphaug, G. (2002). hUNG2 is the major repair enzyme for removal of uracil from U:A matchers, U:G mismatches and U in single stranded DNA, with SMUG1 as a broad specificity backup. J. Biol. Chem. 277, 39926-39936.
Aas, P.A., Otterlei, M., Falnes, P.Ø., Vågbø, C.B., Skorpen, F., Akbari, M., Sundheim, O., Bjørås, M., Slupphaug, G., Seeberg, E. and Krokan, H.E. (2003). Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA. Nature 421; 859-863
Imai, K, Slupphaug, G., Lee, W-I., Revy, P., Nonoyama, S, Catalan, N, Yel, L., Forveille, M., Kavli, B., Krokan, H.E., Ochs, H.D., Fischer, A. and Durandy, A. (2003) Uracil-DNA glycosylase deficiency profoundly impairs immunoglobulin class switch. Nature Immunology 4:1023-1028
Akbari, M., Otterlei, M., Peña-Diaz, J., Kavli, B., Hagen, L., Liabakk, N.B., Imai, K., Durandy, A., Slupphaug G., and Krokan, H.E. (2004) An affinity-isolated UNG2-associated repair complex carries out complete repair of U/G mispairs and U/A pairs in DNA. Nucl. Acids Res. 32:5486-98
Kavli, B., Andersen, S., Otterlei, M., Liabakk, N., Durandy A., Imai, K., Krokan H.E., and Slupphaug, G.(2005) Lymphoid cell lines from UNG deficient HIGM patients have profoundly impaired uracil excision activity from single stranded DNA and increased levels of uracil in the chromosome. J. Exp. Med. 201, 2011-2021
Andersen, S., Ericsson, M., Dai, HY, Peña-Diaz, J., Slupphaug, G., Nilsen, H., Aarset, H. and Krokan, H.E. (2005) Monoclonal B-cell hyperplasia and leukocyte imbalance precede development of B-cell malignancies in uracil-DNA glycosylase deficient mice. DNA Repair 4:1432-1441.
Auerbach, P., Bennett, A.O., Bailey, E., Krokan, H,E. and Demple, B. (2005) Mutagenic specificity of endogenously-generated abasic sites in Saccharomyces cerevisiae chromosomal DNA. Proc. Natl. Acad. Sci. USA..102:17711-17716.
Ringvoll,J., Nordstrand, L.M., Vågbø, C. B. Talstad, V., Reite,K., Aas, P.A., Lauritzen, K. H., Liabakk, N.B., Bjørk, A., Doughty, R.W., Falnes, P., Krokan, H.E. and Klungland, A. (2006) Repair deficient mice reveal mABH2 as the primary oxidative demethylase for repairing endogenous and induced 1meA and 3meC lesions in DNA. EMBO J. 25:2189-2198.
Sundheim, O., Vågbø, C.V., Bjørås, de Sousa, M.M.L., Aas, P.A., Drabløs, Krokan, H.E., Tainer, J.A. and Slupphaug, G. (2006). Human ABH3 structure and key residues for oxidative demethylation to reverse DNA/RNA damage. EMBO J. 25:3389-3397
Akbari, M., Otterlei, M., Peña-Diaz, J., and. Krokan, H.E. (2007) Different organization of base excision repair of uracil in DNA in nuclei and mitochondria and selective upregulation of mitochondrial uracil-DNA glycosylase after oxidative stress. Neuroscience 6:505-516
Pettersen, H.S., Sundheim, O., Gilljam, K.; Slupphaug, G., Krokan, H.E. and Kavli, B. (2007) Uracil-DNA glycosylases SMUG1 and UNG2 coordinate the initial steps of Base Excision Repair by distinct mechanisms. Nucl. Acids. Res.35: 3879-3892.
Kavli, B., Otterlei, M., Slupphaug, G. and Krokan, H.E.(2007) DNA-General mutagen, but normal intermediate in acquired immunity. DNA Repair (Amst). 6:505-516
Hagen, L., Kavli, B., Sousa, M. M.L., Diaz, J.P., Liabakk, N.B., Aslaksen, P.B., Torseth, K., Sundheim, O., Otterlei, M., Hørning, O., Jensen, O.N., Krokan, H.E. and Slupphaug, G. (2008) Cell Cycle Regulated Phosphorylations of Human Uracil-DNA Glycosylase UNG2 Govern Replication-Associated Uracil Removal EMBO J. 27:51-61
Akbari, M., Visnes, T., Krokan, H.E. and Otterlei, M. (2008) Base excision repair by human mitochondrial extracts involves both single-nucleotide insertion and long-patch DNA synthesis. DNA Repair 7:605-616
Hung, R.J., McKay, J.D., Gaborieau, V., Boffetta, P., Hashibe, M., Earidze, D., …Krokan, H.E.,… Lathrop, M., Brennan, P. (2008) A genome-wide association study identifies a susceptibility locus for lung cancer encompassing nicotinic acetylcholine receptor subunit genes on 15q25. Nature 452:633-637(multicenter study with 6 centers, several author names deleted to save space)
Westbye, M.P., Feyzi, E., Aas, P.A., Vågbø, C.B., Kavli, B., Talstad, V.A., Hagen, L., Sundheim, O., Liabakk, N-B., Slupphaug, G., Otterlei, M., Krokan, H.E.(2008) Human AlkB homologue 1 is a mitochondrial protein that repairs 3-methylcytosine in DNA. J Biol Chem 283:25046-25056
McKay, J.D., Hung, R.J. , Gaborieau, V., Boffetta, P., (authors deleted), Krokan, H.E., Skorpen, F., Elvestad, M.B., Vatten, L.,…(authors deleted) Lathrop, M., Brennan, P. (2008) Identification of gene region 5p15.33, comprising the telomerase reverse transcriptase gene, as a novel lung cancer susceptibility locus among 6,000 lung cancer cases and 9,500 controls. Nature Genetics 40:1404-1406 (multicenter study with 6 centers, several author names deleted to save space)
Sundheim, O., Talstad, V.A., Vågbø, C.B., Slupphaug, G., Krokan, H.E. (2008) AlkB demethylases flip out in different ways. DNA Repair 7:1916-1923
Visnes, T., Doseth, B., Pettersen, H.S.,
Vitenskapelig, faglig og kunstnerisk arbeid
Et utvalg av nyere tidsskriftspublikasjoner, kunstneriske produksjoner, bok, inklusiv bokdeler og rapport-del. Se alle publikasjoner i databasen
Tidsskriftspublikasjoner
- (2020) Targeting OGG1 arrests cancer cell proliferation by inducing replication stress. Nucleic Acids Research. vol. 48 (21).
- (2019) Uracil-DNA glycosylase UNG1 isoform variant supports class switch recombination and repairs nuclear genomic uracil. Nucleic Acids Research. vol. 47 (9).
- (2018) Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation. Science. vol. 362 (6416).
- (2017) Uracil Accumulation and Mutagenesis Dominated by Cytosine Deamination in CpG Dinucleotides in Mice Lacking UNG and SMUG1. Scientific Reports. vol. 7 (1).
- (2016) Photodynamic treatment with hexyl-aminolevulinate mediates reversible thiol oxidation in core oxidative stress signaling proteins. Molecular Biosystems.
- (2016) DNA base modifications in honey bee and fruit fly genomes suggest an active demethylation machinery with species- and tissue-specific turnover rates. Biochemistry and Biophysics Reports. vol. 6.
- (2016) Excerpts from the 1st international NTNU symposium on current and future clinical biomarkers of cancer: innovation and implementation, June 16th and 17th 2016, Trondheim, Norway. Journal of Translational Medicine. vol. 14:295.
- (2016) Uracil-DNA glycosylase UNG promotes tet-mediated DNA demethylation. Journal of Biological Chemistry. vol. 291 (2).
- (2015) Identification of lung cancer histology-specific variants applying Bayesian framework variant prioritization approaches within the TRICL and ILCCO consortia. Carcinogenesis. vol. 36 (11).
- (2015) Cell cycle regulation of human DNA repair and chromatin remodeling genes. DNA Repair. vol. 30.
- (2015) AID expression in B-cell lymphomas causes accumulation of genomic uracil and a distinct AID mutational signature. DNA Repair. vol. 25.
- (2014) Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer. Nature Genetics. vol. 46 (7).
- (2014) Red versus blue light illumination in hexyl 5-aminolevulinate photodynamic therapy: the influence of light color and irradiance on the treatment outcome in vitro. Journal of Biomedical Optics. vol. 19:088002 (8).
- (2014) Activation-induced cytidine deaminase (AID) is localized to subnuclear domains enriched in splicing factors. Experimental Cell Research. vol. 322 (1).
- (2014) Error-free versus mutagenic processing of genomic uracil-Relevance to cancer. DNA Repair. vol. 19.
- (2014) Expression and recruitment of uracil-DNA glycosylase are regulated by E2A during antibody diversification. Molecular Immunology. vol. 60 (1).
- (2014) Protozoan ALKBH8 Oxygenases Display both DNA Repair and tRNA Modification Activities. PLOS ONE. vol. 9 (6).
- (2013) The causal role of smoking in anxiety and depression: a Mendelian randomization analysis of the HUNT study. Psychological Medicine. vol. 43 (4).
- (2013) Transcription profiling during the cell cycle shows that a subset of Polycomb-targeted genes is upregulated during DNA replication. Nucleic Acids Research. vol. 41 (5).
- (2013) Association between a 15q25 gene variant, nicotine-related habits, lung cancer and COPD among 56 307 individuals from the HUNT study in Norway. European Journal of Human Genetics. vol. 21 (11).