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Kari Espolin Fladmarks bilde

Kari Espolin Fladmark

Professor
  • E-postKari.Fladmark@uib.no
  • Telefon+47 55 58 45 14
  • Besøksadresse
    Thormøhlensgt. 53 A/B
  • Postadresse
    Postboks 7803
    5020 Bergen

 

Vår forskningsgruppe prøver å forstå hvordan stress fører til celledød og hvilke mekansimer cellene har for å beskytte seg selv og omliggende celler. Vi bruker zebrafisk som in vivo modell for å studere signaler som fører til celledød og beskyttelse. Zebrafisk er blitt en svært populær modell for menneskelig sykdommer. Zebrafiskens utvikling og organer er like våre og sykdomsrelaterte menneskelige gener finnes som funksjonelle gener også i zebrafisk.

Vitenskapelig artikkel
  • 2019. Dysregulation in the Brain Protein Profile of Zebrafish Lacking the Parkinson’s Disease-Related Protein DJ-1. Molecular Neurobiology. 1-17.
  • 2018. Astroglial DJ-1 over-expression up-regulates proteins involved in redox regulation and is neuroprotective in vivo. Redox Biology. 237-247.
  • 2016. Quantitative proteomics analysis of zebrafish exposed to sub-lethal dosages of β-methyl-amino-L-alanine (BMAA). Scientific Reports.
  • 2015. The N-terminal acetyltransferase Naa10 is essential for zebrafish development. Bioscience Reports. 10 sider.
  • 2015. Algal toxin azaspiracid-1 induces early neuronal differentiation and alters peripherin isoform stoichiometry. Marine Drugs. 7390-7402.
  • 2013. Identification of dynamic changes in proteins associated with the cellular cytoskeleton after exposure to okadaic acid. Marine Drugs. 1763-1782.
  • 2013. Comparative analysis of IgM sub-variants in salmonid fish and identification of a residue in mu 3 which is essential for MAb4C10 reactivity. Fish and Shellfish Immunology. 667-672.
  • 2012. Nodularin exposure induces SOD1 phosphorylation and disrupts SOD1 co-localization with actin filaments. Toxins. 1482-1499.
  • 2012. Impact of dietary protein hydrolysates on skeleton quality and proteome in Diplodus sargus larvae. Journal of Applied Ichthyology. 477-487.
  • 2012. Ectopic expression of Flt3 kinase inhibits proliferation and promotes cell death in different human cancer cell lines. Cell Biology and Toxicology. 201-212.
  • 2012. Dietary lysine imbalance affects muscle proteome in zebrafish (Danio rerio): a comparative 2D-DIGE study. Marine Biotechnology. 643-654.
  • 2010. Increased interaction between DJ-1 and the Mi-2/nucleosome remodelling and deacetylase complex during cellular stress. Proteomics. 1494-1504.
  • 2009. Proteomic response of human neuroblastoma cells to azaspiracid-1. Journal of Proteomics. 695-707.
  • 2009. Ligand-induced Flt3-downregulation modulates cell death associated proteins and enhances chemosensitivity to idarubicin in THP-1 acute myeloid leukemia cells. Leukemia Research. 276-287.
  • 2009. Acyloxymethyl esterification of Nodularin-R and Microcystin-LA produces inactive protoxins that become reactivated and produce apoptosis inside intact cells. Journal of Medicinal Chemistry. 5758-5762.
  • 2008. Identification of protein interaction partners by immunoprecipitation: Possible pitfalls and false positives. Experimental and Clinical Hepatology. 16-22.
  • 2008. Identification of a novel phosphorylation site of acyl-CoA binding protein (ACBP) in nodularin-induced apoptotic hepatocytes. Experimental Cell Research. 2141-2149.
  • 2007. Comprehensive analysis of exported proteins from Mycobacterium tuberculosis H37Rv. Proteomics. 1702-1718.
  • 2006. CaM-kinasell-dependent commitment to microcystin-induced apoptosis is coupled to cell budding, but not to shrinkage or chromatin hypercondensation. Cell Death and Differentiation. 1191-1202.
  • 2004. Caspase-dependent, geldanamycin-enhanced cleavage of co-chaperone p23 in leukemic apoptosis. Leukemia. 1989-1996.
  • 2003. Changed energy state and increased mitochondrial beta-oxidation rate in liver of rats associated with lowered proton electrochemical potential and stimulated uncoupling protein 2 (UCP-2) expression. Journal of Biological Chemistry. 30525-30533.
  • 2003. Changed Energy State and Increased Mitochondrial B-Oxidation Rate in Liver of Rats Associated with Lowered Proton Electrochemical Potential and Stimulated Uncoupling Protein 2 (UCP-2) Expression. Journal of Biological Chemistry. 30525-30533.
  • 2002. Ca2+/calmodulin dependent protein kinase II is required for microcystin-induced apoptosis. Journal of Biological Chemistry. 2804-2811.
  • 2001. Apoptotic effect of cyanobacterial extract on rat hepatocytes and human lymphocytes. Environmental Toxicology. 225-233.
  • 2001. Apoptotic effect of cyanobacterial blooms collected from Polish water reservoirs. International Journal of Occupational Medicine and Environmental Health. 335-344.
  • 2000. An ultrasensitive competitive binding assay for the detection of protein phosphatase directed toxins. Toxicon. 347-360.
  • 1999. Ultrarapid apoptosis inducted by phosphatase inhibitors. Cell Death Differ. Cell Death and Differentiation. 1099-1108.
  • 1999. Caspase I related protease inhibition retards the execution of okadaic acid and camptothecin induced apoptosis and PAI-2 selective cleavage, but not commitment to cell death in HL-60 cells. British Journal of Cancer. 1685-1691.
  • 1999. An ultrasensitive competitive binding assay for the detection of toxins affecting protein phosphatases. Toxicon. 347-360.
  • 1998. Sensitive detection of apoptogenic toxins in suspension cultures of rat and salmon hepatocytes. Toxicon. 1101-1114.
  • 1998. Apoptosis induced by microinjection of cytochrome c is caspase-dependent and is inibited by Bcl-2. Cell Death and Differentiation. 660-668.
  • 1997. Gap junctions and growth control in liver regeneration and in isolated rat hepatocytes. Hepatology. 847-855.
  • 1997. Fas/APO-1 (CD95)-Induced Apoptosis of Primary Hepatocytes Is Inhibited by cAMP. Biochemical and Biophysical Research Communications - BBRC. 20-25.
  • 1995. Ala%3%3%5 is essential for high-affinity cAMP-binding of both sites A and B of cAMP-dependent protein kinase type I. FEBS Letters. 291-294.
  • 1995. ALA-335 is essential for high-affinity cAMP-binding of both sites A and B of cAMP-dependent protein kinase type I. FEBS Letters. 291-294.
Rapport
  • 2006. Shellfish toxin azaspiracid-1 induced changes in cytoskeletal proteins in neuronal cells. .
  • 2006. Oocyte development in Atlantic cod (Gadus morhua L.): Trypsin-like specific activity, capacity for protein synthesis and proteomics. .
Faglig foredrag
  • 2016. Functional Analysis of the DJ-1 Protein Using a CRISPR/Cas9 Knockout of the Park7 Gene in Zebrafish.
Vitenskapelig foredrag
  • 2018. Role of the Parkinsons Disease-related protein DJ-1 in redox control and neuronal protection.
  • 2017. Using zebrafish to understand BMAA-induced neurotoxicity and its relevance to neurodegeneration.
  • 2011. The muscle proteome of growing fish is affected by dietary lysine.
  • 2009. Saxitoxin biosynthesis in organisms from two kingdoms - horizontal gene transfer or parallel evolution?
  • 2008. Identification of DJ1 interaction partners using a quantitative proteomics tool.
  • 2006. Late breaker: Revealing the secreted proteome of Mycobacterium tuberculosis H37Rv.
  • 2003. cAMP induced protein phosphorylation in acute myelogenous leukemia cells.
  • 2002. Protein phosphatases as targets in natural compounds-induced apoptosis.
  • 2002. Bioactive compounds from cyanobacteria.
  • 1998. Ultrarapid apoptosis induction in a variety of cell types injected with phosphatase inhibitors is mediated through Ca2 /calmodulin dependent protei kinase activity.
  • 1998. Marine cyanobacteria as a source for bioactive (apoptosis-modifying) compounds with potential as cell biology reagents and drugs.
  • 1998. Distinct apoptotic death forms. Distinct pathways and functions?
Mastergradsoppgave
  • 2019. Impact of cysteine 106 oxidation on function and localisation of the Parkinson’s disease-related protein DJ-1.
  • 2017. The protective function of L-serine in a zebrafish model of B-methylamino-L-alanine induced toxicity.
  • 2015. Neuronal DJ-1 functions in a zebrafish model for Parkinson’s Disease.
  • 2015. Effects of β-methylamino-L-alanine (BMAA)on brain-derived cell lines and zebrafish.
  • 2013. Mechanistic studies of Atlantic cod responses to alkyl-substituted naphthalene and phenanthrene.
  • 2012. Role of the Parkinson´s disease-related protein DJ-1 in oxidative stress-induced cell death.
  • 2011. DJ-1 expression and function in AML cell lines.
  • 2009. Apoptosis-related post translational modifications of endoplasmic reticulum protein-57 (ERp57).
  • 2007. A study on the Parkinson’s disease related DJ-1 protein. Possible function and involvement in algal toxin-induced apoptosis.
  • 2005. Role of Cu/Zn superoxide dismutase (SOD1) in phosphatase inhibitor-induced apoptosis.
Populærvitenskapelig artikkel
  • 2003. PROBE-nasjonal plattform i proteomikk. NBS-nytt. 23-24.
  • 2001. Biologisk baserte blåskjelltester (BBB). Fiskehelse. 26-33.
Doktorgradsavhandling
  • 2019. Functional importance of the Parkinson’s disease-related protein DJ-1.
  • 2015. Cellular responses to algal toxins.
  • 2011. The cellular distress proteome. A quantitative study of oxidativily stressed cells.
  • 1998. Hepatocyte proliferation and apoptosis-regulation by cell communication and phosphorylation. -.
Intervju
  • 2019. Denne fisken vil trolig få Parkinson.
  • 2016. Studerer sebrafisk for å finne Parkinsonsvar.
  • 2016. Sebrafrisk Glem laboratorierotta. Nå er sebrafisken forskernes nye favoritt i kampen mot både fysiske og psykiske sykdommer.
Programdeltagelse
  • 2015. Death - a series about life.
Vitenskapelig Kapittel/Artikkel/Konferanseartikkel
  • 2014. Proteomic tools to elucidate the molecular action of micro-algal toxins. 21 sider.
Sammendrag/abstract
  • 2018. The protein cargo of endothelial cell-derived extracellular vesicles released in response to IL-3 identifies the Wnt signaling pathway as a relevant mediator of inflammation. Journal of Extracellular Vesicles.
  • 2006. Proteomic tissue imaging for rapid brain biomarker discovery. European Journal of Neurology. 42-42.
Poster
  • 2018. naa10 knockdown and NatA inhibition point to role for the NatA complex in zebrafish dorsoventral axis formation .
  • 2018. Functional Analysis of the DJ-1 Protein Using a CRISPR/Cas9 Knockout of the Park7 Gene in Zebrafish.
  • 2016. A protective function of increased glial DJ-1 expression in a zebrafish model of Parkinson’s disease.
  • 2015. The N-terminal acetyltransferase Naa10 is essential for zebrafish development.
  • 2015. High-definition quanlitative and quantitative proteomics of a Parkinson´s disease zebrafish model.
  • 2014. Functional Mechanisms Behind the Oxidative Stress Protective Action of DJ-1.
  • 2013. Proteome profiling of zebrafish embryos with glial specific over-expression of the Parkinson’s disease-related protein DJ-1.
  • 2011. Growth and skeletal muscle proteome of juvenile zebrafish is affected by a dietary lysine.
  • 2008. The hyperthermophilic sulfate-reducing archaeon Archaeoglobus fulgidus; a proteomics study on the shift between chemoorganoheterotrophic and chemilithoautotrophic growth.
  • 2008. Protein expression changes in human neuroblastoma cells treated with azaspiracid-1.
  • 2008. DJ-1 interacts with the chromatin remodelling complex NuRD to regulate apoptotic cell death.
  • 2006. Oocyte development in Atlantic cod (Gadus morhua L.): Trypsin-like specific activity, capacity for protein synthesis and proteomics.
  • 2006. Comparing the protein identifications obtained using two-dimensional gel electrophoresis or liquid chromatography mass spectrometry on the secreted proteome of Mycobacterium tuberculosis.
  • 2003. Differential Expression of Splicing factor SR proteins and Their phosphorylation in Cell Stress leading to Apoptosis.
  • 2002. Protein phosphatase 2A as a receptor for diarrhetic shellfish poisoning (DSP) toxins- Development of a sensitive in vitro assay.
  • 2002. Phosphorylated targets in ultrarapidly induced apoptosis.
  • 1997. Detedtion of toxins from marine cyanobacteria based on their affinity for protein phosphatase 2A and their ability to induce apoptosis in salmon hepatocytes.
Vitenskapelig oversiktsartikkel/review
  • 2017. European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS). 94-162.
  • 2015. Redox control of protein degradation. 409-420.
  • 2006. Proteomics approaches to elucidate oncogenic tyrosine kinase signaling in myeloid malignancies. 185-198.
  • 2006. Algal toxins as guidance to identify phosphoproteins with key roles in apoptotic cell death. 209-215.

Se fullstendig oversikt over publikasjoner i CRIStin.

Dysregulation in the brain protein profile of zebrafish lacking the Parkinson’s disease related protein DJ-1. Edson, A.J., Hushagen, H.A., Frøyset, AK., Elda, I., Khan, E.A., Di Stefano, A., Fladmark, K.E. (2019)  Mol. Neurobiol. DOI: 10.1007/s12035-019-01667-w

Astroglial DJ-1 over-expression up-regulates proteins involved in redox regulation and is neuroprotective in vivo. Frøyset AK Edson AJ, Gharbi N, Khan EA, Dondorp D, Bai Q, Tiraboschi E, Suster ML, Connolly JB, Burton EA, and Fladmark KE. (2018) Redox Biol. 16:237-247.

Quantitative proteomics analysis of zebrafish exposed to sub-lethal dosages of BMAA. Frøyset AK, Khan EA, Fladmark KE (2016)  Sci Reports 6:29631.

Redox control of protein degradation. Pajares M, Jimineze-Moreno N, Dias I, Debelec B, Vucetic M, Fladmark KE, Basaga H, Ribaric S, Milisav I, Cuadrado A (2015)  RedOx Biology 6:409-20.

The Algal Toxin Azaspiracid-1 Induces an Early Neuronal Differentiation and Alters Peripherin Isoform Stoichiometry . Hjørnevik LV , Frøyset AK, Grønset TA, Rungruangsak-Torrissen K,  and Fladmark KE (2015)  Marine Drugs 13, 7390-7402.

The N-terminal acetyltransferase Naa10 is essential for zebrafish development. Ree RM, Myklebust L, Thiel P, Foyn H, Fladmark KE, and Arnesen T (2015)  Bioscience Reports Aug. 6

Proteomic tools to elucidate the molecular action of microalgal toxins. In Toxins and biologically active compounds from microalgae. Ed Rossini GP Fladmark KE (2014) (Book chapter)

Identification of dynamic changes in proteins associated with the cellular cytoskeleton after exposure to okadaic acid. Opsahl JA, Ljostveit S, Solstad T, Risa K, Roepstorff P, and Fladmark KE (2013) Marine Drugs11:1763-82.

Comparative analysis of IgM sub-variants in salmonid fish and identification of a residue in m3 which is essential for MAb4C10 reactivity. KamilA, RaaeA, Fjelldal PG, Koppang EO, Fladmark KE, Hordvik I (2013)Fish and Shellfish Immunology 34: 667-72.

Nodularin exposure induces SOD1 phosphorylation and distrupts SOD1 co-localization with actin. Hjørnevik LV, Fismen L, Young FM, Solstad T , Fladmark KE (2012) . Toxins 4:1482-1499.

Dietary lysine imbalance affects muscle proteome in zebrafish (Danio rerio): a comparative 2D-DIGE study. de Vareilles M, Conceição L, Gómez-Requeni P, Kousoulaki K, Richard N, Rodrigues P, Fladmark, KE, Rønnestad I, (2012) Marine Biotechnology 14:643-654.

Impact of dietary protein hydrolysates on skeleton quality and proteome in Diplodus sargus larvae. de Vareilles M, Richard N, Gavaia PJ, Silva TS., Cordeiro O, Guerreiro I, Yúfera M, Batista I, Pires C, Pousão-Ferreira P, Rodrigues PM, Rønnestad I, Fladmark KE, Conceição LEC (2012) J Appl Ichthyol 28: 477-87.

Ectopic expression of Flt3 kinase inhibits proliferation and promotes cell death in different human cancer cell lines Oveland E, Wergeland L, Hovland R, Lorens JB, Gjertsen BT, Fladmark KE. Cell Biol Toxicol. 2012 Mar 16.

Increased interaction between DJ-1 and the Mi-2/ nucleosome remodelling and deacetylase complex during cellular stress. Opsahl JA, Hjornevik LV, Bull VH, Fismen L, Froyset AK, Gromyko D, Solstad T, Fladmark KE. Proteomics. 2010;10(7):1494-504.

Acyloxymethyl Esterification of Nodularin-R and Microcystin-LA Produces Inactive Protoxins that Become Reactivated and Produce Apoptosis inside Intact Cells. Herfindal L, Kasprzykowski F, Schwede F, Lankiewicz L, Fladmark KE, Lukomska J, Wahlsten M, Sivonen K, Grzonka Z, Jastorff B, Døskeland SO J Med Chem 2009 Epub 2009 aug.

Proteomic response of human neuroblastoma cells to azaspiracid-1. Kellmann R, Schaffner CA, Grønset TA, Satake M, Ziegler M, Fladmark KE. J Proteomics. 2009 May 2;72(4):695-707. Epub 2009 Mar 5.

Ligand-induced Flt3-downregulation modulates cell death associated proteins and enhances chemosensitivity to idarubicin in THP-1 acute myeloid leukemia cells. Oveland E, Gjertsen BT, Wergeland L, Selheim F, Fladmark KE, Hovland R. Leuk Res. 2009 Feb;33(2):276-87. Epub 2008 Aug 8.

Identification of a novel phosphorylation site of acyl-CoA binding protein (ACBP) in nodularin-induced apoptotic hepatocytes. Solstad T, Fismen L, Garberg H, Fladmark KE. Exp Cell Res. 2008 Jun 10;314(10):2141-9. Epub 2008 Mar 30.

Comprehensive analysis of exported proteins from Mycobacterium tuberculosis H37Rv. Målen H, Berven FS, Fladmark KE, Wiker HG. Proteomics. 2007 May;7(10):1702-18.

CaM-kinaseII-dependent commitment to microcystin-induced apoptosis is coupled to cell budding, but not to shrinkage or chromatin hypercondensation. Krakstad C, Herfindal L, Gjertsen BT, Bøe R, Vintermyr OK, Fladmark KE, Døskeland SO. Cell Death Differ. 2006 Jul;13(7):1191-202. Epub 2005 Nov 25.

Algal toxins as guidance to identify phosphoproteins with key roles in apoptotic cell death. Solstad T, Fladmark KE. Curr Pharm Biotechnol. 2006 Jun;7(3):209-15. Review.

Proteomics approaches to elucidate oncogenic tyrosine kinase signaling in myeloid malignancies. Oveland E, Fladmark KE, Wergeland L, Gjertsen BT, Hovland R. Curr Pharm Biotechnol. 2006 Jun;7(3):185-98. Review.

Dr. scient, University of Bergen. “Hepatocyte proliferation and apoptosis: regulation by cell communication and phosphorylation” (1998)

Pågående prosjekter:

  • "Role of phosphorylation in regulation of redox-mediated events in apoptotic cell death" (FUGE)
  • "Nordic Network in proteomics" (NordForsk) NORPRO
  • "Kompetanseoppbygging i kvantitativ proteomikk" (Meltzer)
  • "Nordic network in quantitative proteomics" (NordForsk) Q-NORDIC

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