Bakgrunn og aktiviteter

Short CV

BIOGRAPHICAL SKETCH

 

  NAME

  POSITION TITLE

Hans Einar Krokan

Professor/Chairman

EDUCATION/TRAINING

INSTITUTION AND LOCATION

DEGREE
(if applicable)

YEAR(s)

FIELD OF STUDY

University of Oslo, Oslo, Norway

M.D

1970

Medicine

University of Tromsø, Tromsø, Norway

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, University of Tromsø, IMB

1977-1979                  Post doctoral fellow (Fogarty International Fellowship), Harvard Medical School, Dep. Biol. Chem (18 months) with Prof. Melvin L. DePamphilis

1979-1985                  Associate professor in biochemistry, University of Tromsø

1983-1984                  Visiting scientist, (Stipend from International Cancer Union, Eleanor Roosevelt Awardee), National Cancer Institute, Lab. Human Carcinogenesis, Bethesda (12 months) with Dr. C. C. Harris

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 Institute of Biotechnology/UNIGEN, Scientific director of Unigen, University of Trondheim Norwegian College of Technology

1993-present     Professor in medicine/molecular Biology, Medicine, Institute of Cancer Research and Molecular Biology)

1990-2002         Director/Chairman, Institute of Cancer Research and Molecular Biology, Faculty of Medicine, University of Trondheim

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 Hydro AS), and has successfully contributed to drug development, particularly Omacor, the only therapeutic drug developed in Norway. His research group within DNA repair is among the internationally leading groups.

 

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., Blackburn, G.M. and Tainer, J.A. (2000) Uracil-DNA glycosylase-DNA substrate and product structures: Conformational strain promotes catalytic efficiency by coupled stereoelectronic effects.  Proc. Natl. Acad. Sci., USA 97, 5083-5088

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., Hagen, L., Sousa, MML, Akbari, M., Otterlei, M., Kavli, B., Slupphaug, G., and Krokan, H.E. (2009) Uracil in DNA and its processing by different DNA glycosylases. Royal Phil. Transact. B. 364:563-568

 

 

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