Judit Ovadi PhD. D.Sc.

        Research professor

        Institute of Enzymology

        Research Centre for Natural Sciences,

        Hungarian Academy of Sciences,

        H-1113 B u d a p e s t,

        Karolina u. 29-31.

        HUNGARY

        Phone:     (00)36-1-279-3129

        Fax:         (00)36-1-466-5465

        Email:     ovadi@enzim.hu

CV    Projects      Publications        Grants       Coworkers          Collaborators     Links

Projects:

I. MICROCOMPARTMENTS ASSOCIATED WITH MICROTUBULAR NETWORKS

new ultrastructures and functional units in CNS

Background

The development of the conformational diseases, a significant group of the CNS diseases, is initiated by unfolded/misfolded proteins, which enter aberrant interactions resulting in the aggregation and deposition of established and not-yet identified proteins forming pathological inclusions leading to progressive loss of neurons and dementia. The approximately 40 different diseases with mostly neurodegenerative symptoms are ranked into this family of diseases. The two major representatives of the tauo- and synucleinopathies are Alzheimer’s disease (AD) and Parkinson’s disease (PD), respectively. Ultrastructural and energetic aspects of these two relatively common age-related neurological diseases with dramatic socioeconomic impact were targeted by our latest research within the frame of BioSim. The hallmark proteins of PD and AD are alpha-synuclein and Tau/beta-amyloid, respectively, do not have well-defined 3D structures. alpha-Synuclein plays an important role in synaptic plasticity, regulation of vesicle transport and neurotransmission, acts as a chaperon and protects neurons against oxidative stress. Tau is a microtubule-associated protein abundant in neurons, and controls microtubule stability in isoforms- and phosphorylation-dependent manner. Hyperphosphorylation of the Tau proteins, however, can result in the self-assembly of tangles of paired helical filaments and straight filaments (Tau inclusions).

TPPP/p25 a new unstructured Microtubule Associated Protein

TPPP/p25 was isolated and identified as an intrinsically unstructured protein, the primary target of which is the microtubule system and it was designated as Tubulin Polymerization Promoting Protein on the basis of its in vitro and in vivo functions. TPPP/p25 seems to control the dynamism and stability of the microtubule system, causing resistance of TPPP-bundled MTs against anti-microtubular agents, thus it likely displays significant influence on microtubule-related physiological and pathological events. Molecular mechanisms responsible for these effects have been recently identified, these are TPPP/p25 promoted specific acetylation and bundling of the microtubule ultrastructures. Thus we proposed that the potential function of this protein resembled that of MAPs. It is mainly expressed in oligodendrocytes; however, TPPP gene(s) are conserved in the genomes of ciliated organisms, but are lacking from the non-ciliated ones. Cilia (flagella) are microtubule-based cellular extensions of sensory and/or motile function. TPPP orthologs are among the only 16 genes that can be found in all ciliated organisms, suggesting that TPPP orthologs may be associated with a basic function of cilia.

Protein phosphorylation has a significant impact in the etiology of neurodegenerative processes. For example, tau and alpha-synuclein, the major hallmarks of Parkinson and Alzheimer diseases, respectively, are targets of different protein kinases. The phosphorylation of TPPP/p25 resulted in the loss of its microtubule-assembling activity due to its interaction with ERK2 which phosphorylates Thr14 and/or Ser18 in its unfolded N-terminal tail.

Our immunofluorescent data on HeLa cell and immunohistochemistry on human brain samples from patients suffering in synucleinopathies provided evidence for the co-enrichment of TPPP with tubulin in aggresome, Lewy body and other inclusions. TPPP/p25 was found to impede the formation of large amorphous protein aggregates. TPPP/p25 molecules are predominantly in unphosphorylated form in the inclusions suggesting possible pathological relevance of the post-translational modification of TPPP/p25.

TPPP/p25 a key factor for oligodendrocyte myelinisation

TPPP/p25 is endogenously expressed in myelinating oligodendrocytes of the central nervous system (CNS). Our recent single cell experiments using TPPP/p25 siRNAs or specific microRNA (miR-206) demonstrated that TPPP/p25 expression is crucial for the differentiation of oligodendrocytes leading to due to its role in the rearrangement of the microtubular network during the process elongation prior to the onset of myelination. The formation and maintenance of the dynamics of the microtubular system during differentiation, cell polarization and migration rely on the pronounced reorganization of the cytoskeleton.

We demonstrated that the expression of TPPP/p25 in HeLa cells, doxycycline-inducible CHO cells and in the oligodendrocyte CG-4 cells promoted the acetylation of alpha-tubulin at residue Lys-40, whereas its down-regulation by specific siRNAs in CG-4 cells or by the withdrawal of doxycycline from CHO cells decreased the acetylation level of alpha-tubulin. Our results indicate that TPPP/p25 binds to histone deacetylase 6 (HDAC6), responsible for tubulin deacetylation. The binding of TPPP/p25 to HDAC6 was demonstrated by surface plasmon resonance measurements. A typical sensogram is shown in this diagram with the fitted curve to obtain steady state (equilibrium) value of bound TPPP/p25 (RU). The steady-state values were plotted as function of TPPP/p25 concentration to evaluate the apparent dissociation constant (K_d) of the heteroassociation of HDAC6 with TPPP/p25, which was found to be 130 (±50) nM.  The counteracting effect of tubulin on the interaction of TPPP/p25 with HDAC6, is presented by the displacement curve which indicate that the TPPP/p25 complexed with tubulin does not associate with HDAC6.

Moreover we demonstrated that the direct interaction of these two proteins resulted in the inhibition of the deacetylase activity of HDAC6. The measurement of HDAC6 activity showed that TPPP/p25 is able to induce almost complete (90%) inhibition at 3mM concentration. In addition, treatment of the cells with nocodazole, vinblastine or cold exposure revealed that microtubule acetylation induced by Trichostatin A, a well known HDAC6 inhibitor, does not cause microtubule stabilization. In contrast, the microtubule bundling activity of TPPP/p25 was able to protect the microtubules from depolymerization.  Finally, we demonstrated that, similarly to other HDAC6 inhibitors, TPPP/p25 influences the microtubule dynamics by decreasing the growth velocity of the microtubule plus ends and also affects cell motility as demonstrated by time-lapse video experiments. Thus we suggest that TPPP/p25 plays a crucial role in the regulation of the microtubule organization.

We have postulated that in addition to the bundling activity of TPPP/p25, its tubulin acetylation-promoted activity affects the dynamics of the microtubule systems; consequently the reversible post-translational acetylation of a-tubulin on residue Lys-40 can regulates cell differentiation, polarization and migration.  Thus TPPP/p25 likely displays potential role in remyelination of the axons in the normal neurons which is derived by the differentiation and migration of oligodendrocyte precursor cells, and any defect of this complex process leads to the development of multiple sclerosis, an idiopathic chronic inflammatory demyelinating disease of the central nervous system.

Unfolded proteins and energy metabolism: modelling

The relationship of the expression of the unfolded/misfolded proteins and their effects on the energy metabolism was also an objective of our recent research since it is poorly discovered field in spite of the fact that its control is tightly coupled with the functions of several metabolic and signalling pathways. We have performed studies on human cells as well as on brain tissues of transgenic mice expressing unfolded proteins using different approaches to narrow this gap. The major energy source in brain is the glucose metabolized via the glycolysis in the cytosol coupled with the terminal oxidation via the Krebs cycle in the mitochondrium producing ATP as key fuel for many metabolic and signalling pathways. The functioning state of mitochondria of the living cells expressing TPPP/p25 was studied by fluorescent microscopy following tetramethylrhodamine ethyl ester staining by monitoring the polarization state of mitochondrial membrane related to the energy state of the mitochondria. We found that K4 cells, stably expressing EGFP-TPPP/p25, showed strikingly high fluorescence intensity as compared to the control SK-N-MC cells suggesting that the TPPP/p25 expression did not cause energy impairment but enhanced the membrane polarization state. Consistent with this, the ATP concentration was found to be higher in the extract of the K4 cells as compared to that of the control cells. The flux analysis of the glucose metabolism revealed that the enhanced ATP concentration was, at least partly, due to the activation of some key glycolytic enzymes. These data suggest that the stable expression of TPPP/p25 at level which is well tolerated by K4 cells sets up an increased energy state.

Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by multifarious dysfunctional alterations including mitochondrial impairment. To characterize the effect of the unfolded mutant huntingtin protein with CAG trinucleotide repeat disorders on the bioenergetics, HD and normal mice were characterized clinically; the affected brain regions were identified by immunohistochemistry and used for biochemical analysis of the ATP-producing systems in the cytosolic and the mitochondrial compartments. By contrast to most of the speculation in the literature, our results showed that the neuronal damage in HD tissue was associated with increased energy metabolism at the tissue level leading to elevated ATP level coupled with altered levels of various intermediary metabolites resulting in pathological consequences. We developed a new strategy to identify the molecular mechanism responsible for the suspention of energy deficit at system level. This strategy is based upon the comparison of the fluxes measured experimentally and computed by using kinetic parameters of the individual enzymes determined experimentally as well. The biosimulation data revealed that the reduction of the GAPDH activity due its association to the unfolded tail of the mutant huntingtin protein was over-compensated at system level by microcompartmentation of triosephosphates of the glycolytic pathway.

The multifactorial character of conformational diseases such as the interrelationship between the etiology of metabolic and neurological disorders has been elucidated. Recently we proposed that the triosephosphate isomerase deficiency display features characteristics for conformational diseases. In fact, TPI deficiency is an autosomal recessive multisystem genetic disease coupled with hemolytic anemia and neurological disorder frequently leading to death in early childhood. Various genetic mutations of this enzyme have been identified; the mutations result in decrease in the catalytic activity and/or the dissociation of the dimers into inactive monomers. The impairment of TPI activity due to the mutation apparently does not affect the energy metabolism at system level. It results in accumulation of dihydroxyacetone phosphate followed by its chemical conversion into the toxic methylglyoxal, leading to the formation of advanced glycation end products as well as to formation of aberrant protein-protein interaction, sticking to microtubule system leading to the formation of an aggregation-prone protein, a typical characteristic of conformational disorders.

Related references

Hlavanda E, Klement E, Kókai E, Kovacs J, Vincze O, Tőkési N, Orosz F, Medzihradszky KF, Dombradi V, Ovádi J

Phosphorylation blocks the activity of tubulin polymerization promoting protein (TPPP): Identification of sites targeted by different kinases

^{J Biol Chem (2007) 282, 29531-29539}         

Kovács G G, Gelpi E, Lehotzky A, Hoftberger R, Erdei A, Budka H, Ovádi J.

The brain-specific protein TPPP/p25 in pathological protein deposits of neurodegenerative diseases

            Acta Neuropathol (Berl) (2007) 113, 153-61

Keller, A., J. Peltzer, J., Carpentier, G., Horváth, I., Oláh, J., Duchesnay, J.,Orosz, F., Ovádi, J.

            Interactions of enolase isoforms with microtubules during myogenesis

^{BBA-Gen Subjects (2007) 1770, 919-926}

^{Preusser M, Lehotzky A, Budka H, Ovádi J, Kovács G.G.}

^{TPPP/p25 in brain tumours: expression in non-neoplastic oligodendrocytes but not in oligodendroglioma cells}

                ^{Acta Neuropathol (Berl) (2007) 113, 213-215}

^{Steták A, Veress R, Ovádi J, Csermely P, Kéri Gy, Ullrich A.}

                ^{Nuclear translocation of Pyruvate-Kinase M2 isoform induces programmed cell death}

                ^{Cancer Res (2007) 67, 1602-1608}

Lehotzky A, Tőkési N, Gonzalez-Alvarez I, Merino V, Bermejo M, Orosz F, Lau P, Kovacs GG, Ovádi J.

Progress in the development of early diagnosis and a drug with unique pharmacology to improve cancer therapy

            Philos Trans Soc A (2008) 366, 3599-3617

Olah J, Klivenyi P, Gardian G, Vecsei L, Orosz F, Kovacs GG, Westerhoff HV, Ovadi J.

            Increased glucose metabolism and ATP level in brain tissue of Huntington's disease

            transgenic mice

            FEBS J (2008) 275, 4740-4755

Orosz F, Ovádi J.

            TPPP/p25 orthologs are ciliary proteins

            FEBS Letters (2008) 582, 3757-3764

Ovádi J

            The tubulin polymerization promoting protein, TPPP/p25.: My favorite protein

            IUBMB Life (2008) 60, 637-642

Papanastasiou I.B, Foscolos G.B, Tsotinis A, Oláh J, Ovadi J, Prathalingam S.R, Kelly J

            Conformationally constrained adamantaneoxazolines of pharmacological interest

            Heterocycles (2008) 75, 2043-2061

Gonzalez-Alvarez I, Gonzalez-Alvarez M, Oltra-Noguera D, Merino V, Tőkesi N, Ovadi J, Bermejo M.

Unique Pharmacology of KAR-2, a Potential Anti-cancer Agent: absorption modelling and selective mitotic spindle targeting

            Eur J Pharm Sci (2009) 36, 11-19

Ovádi J, Orosz F.

An unstructured protein with destructive potential: TPPP/p25 in neurodegeneration

            Bioassays (2009) 31, 676-686

Ovádi, J., Orosz, F. (eds.)

Protein Folding and Misfolding: Neurodegenerative Diseases

            Focus on Structural Biology; 7.  Springer, 2009 pp. 277

Orosz, F., Lehotzky, A., Oláh, J., Ovádi J.

            TPPP/p25: A New Unstructured Protein Hallmarking Synucleinopathies

            In: Protein Folding and Misfolding: Neurodegenerative Diseases

            Focus on Structural Biology; 7 (eds: Ovádi, J., Orosz, F.)

Springer, 2009. pp. 225-250

Orosz, F., Oláh, J., Ovádi, J.

            Triosephosphate isomerase deficiency: new insights into an enigmatic disease

            BBA-Molecular Basis of Disease (2009) 1792(12):1168-1174

Lehotzky, A., Lau, P., Tőkési, N., Muja, N., Hudson, LD., Ovádi, J.

Tubulin Polymerization Promoting Protein (TPPP/p25) is Critical for Oligodendrocyte Differentiation

GLIA (2010) 58, 157-168

Höftberger R, Fink S, Aboul-Enein F, Botond G, Oláh J, Berki T, Ovádi J, Lassmann H, Budka H, Kovacs GG.

Tubulin polymerization promoting protein (TPPP/p25) as a marker for oligodendroglial changes in multiple sclerosis

GLIA (2010) 58(15):1847-57.

Tőkési N, Lehotzky A, Horváth I, Szabó B, Oláh J, Lau P, Ovádi J.

            TPPP/p25 promotes tubulin acetylation by inhibiting histone deacetylase 6

J. Biol. Chem (2010) 285(23):17896-906.

II. DISORDERED PROTEINS WITH DESTRUCTIVE POTENTIALS IN CNS DISEASES

The etiology of the conformational diseases, a significant group of the Central Nervous System (CNS) diseases, is initiated by disordered proteins, which enter aberrant interactions resulting in protein aggregation, form pathological inclusions leading to progressive loss of neurons and dementia. Representatives of these common age-related neurological disorders with dramatic socioeconomic impact are the Alzheimer’s (AD), Parkinson’s (PD) and Huntington’s (HD) diseases. Although the hallmark proteins of these diseases, a-synuclein, hyperphosphorylated tau/b-amyloid and mutant huntingtin are well-known, their pathomechanisms are still obscure. Ultrastructural characterization and energetic aspects at system level were targeted and established by our research within the frame of BioSim. We identified, isolated and cloned a new IUP denoted as Tubulin Polymerization Promoting Protein (TPPP/p25), which is involved in the formation of certain neurodegenerative disorders, and we characterized its and other ones’ destructive potential in the cases of CNS diseases (Ovádi and Orosz, 2009).

The primary target of TPPP/p25 is the microtubule (MT) system, one of the major filaments of the cytoskeleton, which modulates the cell proliferation and motility coupled with energy (ATP) producing processes. In normal brain TPPP/p25 is an active constituent of the differentiation of oligodendrocyte (OLG), a brain specific cell type, the expression of the protein is indispensable for the growing of cell projection and for myelinization of OLGs as we reported by the means of specific siRNA as well as microRNA (Lehotzky et al, 2010). The myelin ensheathment contacting axons ensures the synaptic transmission for the communication between neurons. Defect in these events is the major cause of the etiology of the sclerosis multiplex, consequently, defect in TPPP/p25 level could be a potential biomarker of this CNS disease.

Effect of the IUPs on the intracellular bioenergetics is a poorly discovered field in spite of the fact that it is tightly coupled with the functions of several metabolic and signalling pathways, and its dysfunction has been assessed in several neurodegenerative disorders (Ovádi and Orosz, 2010). Human cell models expressing human TPPP/p25, the over-expression of which in human brain causes degeneration (Kovacs et al., 2007), were used in our experimental setups to characterize the effect of expression of disordered protein on the cell morphology, microtubular ultrastructure, proteosome machinery as well as on the enzymes and the enzyme systems involved in the ATP production in the cytosol and mitochondria. The major intracellular energy source is the glucose metabolized via the glycolysis in the cytosol coupled with the terminal oxidation via the Krebs cycle in the mitochondria producing ATP as key fuel for many structural and functional processes. The energy state of mitochondria in living human cells expressing TPPP/p25 was studied by fluorescent microscopy by monitoring a fluorescent dye-sensitive polarization state of mitochondrial membrane related to the energy state of the mitochondria. The neuronal cells stably expressing TPPP/p25 showed that the expression of the disordered protein did not result in energy deficiency; rather the ATP level was higher than that of the control cells due to the activation of some key glycolytic enzymes (Orosz and Ovádi, 2010).

Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by multifarious dysfunctional alterations including mitochondrial impairment. To clarify whether the mitochondrial dysfunction is coupled with bioenergetic impairment, the brain regions with pathological inclusions in HD transgenic mice expressing human mutant huntingtin protein with an extended unfolded polyglutamine tail were identified by immunohistochemistry, and used for analysis of energy metabolism. Rather surprisingly, our results showed that the inclusion formation in HD brain was associated with increased energy metabolism at the tissue level leading to elevated ATP level coupled with altered metabolite pattern. We developed a new strategy to identify the molecular mechanism responsible for the compensation/over-compensation of energy deficit at system level. This strategy was based upon the comparison of the experimentally measured and computed fluxes evaluated by mathematical modeling using the experimentally determined kinetic parameters of the individual enzymes. The biosimulation data revealed that the activity of a key glycolytic enzyme (glyceraldehyde-3-phosphate dehydrogenase, GAPDH) was reduced due to its association to the unfolded tail of the mutant huntingtin protein; however, this local effect was over-compensated at system level by molecular mechanism, namely by microcompartmentation resulting in normal or even more intensive glycolytic flux. In conclusion, our data indicate that compensation mechanisms can switch on in the diseased cells well before the cell death in order to compensate the destructive potential of the disordered protein (Oláh et al, 2008).

Triosephosphate isomerase (TPI) deficiency is an autosomal recessive multisystem genetic disease coupled with hemolytic anemia and neurological disorder frequently leading to death in early childhood. Various genetic mutations of this enzyme have been identified; the mutations frequently result in decrease in the catalytic activity and/or the dissociation of the dimers into inactive monomers (Orosz et al., 2006). This disease has been typically considered as a metabolic one, however, recently we have proposed that it displays features characteristic for conformational diseases. Our data show that the impairment of TPI activity due to the mutation apparently does not affect the energy metabolism at system level; however, it results in the accumulation of dihydroxyacetone phosphate followed by its chemical conversion into the toxic methylglyoxal, leading to the formation of advanced glycation end products as well as to an aggregation-prone protein and aberrant protein-protein interactions, a typical characteristic of conformational disorders. Consequently, we proposed TPI deficiency not to be ranked to the metabolic but to the conformational diseases, a significant group of the CNS diseases (Orosz et al., 2009).

Related references

Ovádi J, Orosz F.

An unstructured protein with destructive potential: TPPP/p25 in neurodegeneration.

Bioessays  (2009)  31, 676-686.

Kovács G G, Gelpi E, Lehotzky A, Hoftberger R, Erdei A, Budka H, Ovádi J.

         The brain-specific protein TPPP/p25 in pathological protein deposits of neurodegenerative diseases

Acta Neuropathol (Berl) (2007) 113, 153-61

Lehotzky A, Lau P, Tőkési N, Muja N, Hudson LD, Ovádi J

Tubulin Polymerization Promoting Protein (TPPP/p25) is Critical for Oligodendrocyte Differentiation

Glia (2010) 58, 157-168.

Ovádi J, Orosz F (eds.)

Protein folding and misfolding: neurodegenerative diseases (2009)

Springer, Focus on Structural Biology; 7.  Springer, 2009 pp. 277

Oláh J, Klivenyi P, Gardian G, Vécsei L, Orosz F, Kovacs GG, Westerhoff HV, Ovádi J.

         Increased glucose metabolism and ATP level in brain tissue of Huntington's disease transgenic mice

FEBS J (2008) 275, 4740-4755

Orosz F, Oláh J, Ovádi J.

         Triosephosphate isomerase deficiency: facts and doubts

         IUBMB Life (2006) 58, 703-715

Orosz, F., Oláh, J., Ovádi, J.

Triosephosphate isomerase deficiency: new insights into an enigmatic disease

         Biochim Biophys Acta- Molecular Basis of Disease (2009) 1792, 1168-1174.

Grants:

Hungarian National Science Foundation OTKA T-046071

Title: “Physiological and pathological properties of a new brain-specific protein, p25”

Coordinator J.O.

Period: 2004- 2007

Hungarian National Science Foundation OTKA TS-044730

Title: „The role of metal ions in the structure and function of proteins”

Coordinator: Gabor Naray-Szabó

Period: 2003-2005

Hungarian Ministry of Education (OMFB-00701/2003)

Title: “Neurodegeneration in genetically determined defects”

Coordinator: J.O.

Partners: National Blood Transfusion Institute,

Zoological Department, Eötvös Loránd University

Neurological Institute, University of Szeged

Period: 2003-2005

NKFP-MediChem2 1/A/005/2004

Title: “Drug design of on validated target molecules involved in society diseases”

Period: 2004-2006

EU6 „Life Sciences, Genomics and Biotechnology For Health”

FP6-2003-LIFESCIHEALTH-I”-Proposal No 005137

Title: „Biosimulation - A New Tool in Drug Development”

Principal coordinator: Prof. Erik Mosekilde, Technical University of Denmark

J.O. coordinator of Workpackage 11: „Drugs targeting compartmental micropathways” and Workpackage 14: „Biopharmaceutical optimisation of new anti-cancer molecules”

Period:2005-2009

European Cooperation in the field of Scientific and Technical Research: COST Action TD0905: Epigenetics: Bench to Bedside, 2009.

European Commission EuropeAid Cooperation Office Latin America Directorate EuropeAid/129-877/C/ACT/RAL-1 ALFA III, Segunda Fase DCI-ALA/2010/10/29 Red para el desarrollo de metodologias biofarmaceuticas racionales que incrementen la competencia y el impacto social de las Industrias Farmaceuticas Locales. (Red-Biofarma)

Hungarian National Scientific Research Fund Grants OTKA T-067963: Structure, function and pathology of TPPP/p25 protein family.

Hungarian National Scientific Research Fund Grants OTKA PD 76793 (to J. Olah): Energy metabolism in conformational diseases: Experiments and biosimulation.

Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (to J. Olah)

National collaborators:

Prof. János Kovács ELTE Faculty of Sciences Dept. of Zoology, Budapest (electron microscopy)

Prof. Lajos László ELTE Faculty of Sciences Dept. of Zoology, Budapest (immunhistochemistry)

Prof. Susan Hollán Haematology Institute, Budapest (TPI deficient patients)

Prof. Gábor Náray-Szabó ELTE Faculty of Sciences Theoretical Chemistry, Budapest (crystallography)

Dr.György Keserű Gedeon Richter Ltd., Budapest (molecular modelling)

Dr. Laszló Tirián Department of Biology, Faculty of Medicine, University of Szeged (Drosophila)

Prof. András Perczel ELTE Faculty of Sciences Dept. of Organic Chemistry, Budapest (NMR)

Prof. Katalin Medzihradszky Biological Research Center, Proteomics Laboratory (mass spectroscopy)

Prof. Ferenc Hudecz ELTE Peptid-Chemistry (peptid syntesis)

Prof. László Vécsei Neurological Institute University of Szeged (transgenic mice )

Prof. Laszló Gráf ELTE Department of Biochemistry, Budapest (tripszin 4)

Prof. László Pukás Biological Research Center, Laboratory of Functional Genomics, Szeged (DNA array)

Prof. Viktor Dombrádi University of Debrecen, Department of Medical Chemistry, Debrecen (fphosphorylation)

Prof. Gábor G. Kovács National Physiatry and Neurology Institute, Budapest (immunohistochemistry)

Research group:

Judit Ovádi	professor	ovadi@enzim.hu	279-3129
Ferenc Orosz	senior researcher	orosz@enzim.hu	279-3120
Judit Oláh	senior researcher	olju@enzim.hu	279-3120
Attila Lehotzky	senior researcher	lehotzky@enzim.hu	279-3141
Emma Hlavanda	technician	hlavanda@enzim.hu	279-3141
István Horváth	abroad	horvathi@enzim.hu	279-3141
Orsolya Vincze	maternal leave	vinor@ludens.elte.hu	279-3141
Natália Tõkési	Ph.D. fellow	sibot22@gmail.com	279-3141
Ágnes Zotter	Ph.D. fellow	zotter@enzim.hu	279-3120

Links:

• Gordon Research Conference on Macromolecular Organization and Cell Function Queen's College, Oxford, U.K. August 15-20, 2004
• (written interview, PDF)
• FP6–2003-LIFESCIHEALTH-I: BioSim
• Encyclopedia of Molecular Medicine, 2001 
• Institute of Enzymology