Homepage of Judit Ovádi

	Judit Ovadi PhD. D.Sc.         Research professor         Institute of Enzymology         Biological Research Center,         Hungarian Academy of Sciences,         H-1113. B u d a p e s t,         Karolina u  29         HUNGARY         Phone: (00)36-1-279-3129         Fax:   (00)36-1-466-5465         e-mail: ovadi@enzim.hu

Projects:

One of our objectives is to understand the molecular mechanism of the development of neurodegenerative processes initiated by unfolded/misfolded proteins, and to affect the aberrant protein-protein interactions leading to formation of inclusions in brain.

Recently we have isolated and identified a new brain-specific protein termed TPPP/p25 (Tubulin Polymerization Promoting Protein) the major target of which is the microtubule system. TPPP/p25 affects the dynamics and stability of microtubule network under physiological conditions. Under pathological conditions it is enriched within inclusions of pathological human brain tissues characteristics for Parkinson but not Alzheimer diseases. We work on the characterization of the structural, functional and pathological features of TPPP/p25, identify its homologous proteins for comparative studies, and search for additional targets.

Triosephosphate isomerase deficiency is an unique glycolytic enzymopathy coupled with neurodegeneration. We have characterized the structure, the association properties of the mutant isomerase, and evaluated the consequences of mutation at metabolic level. Recently we reported that the mutation itself cannot be responsible for the development of neurodegenerative sympthoms and for the early death of patients. We are searching factors that play predominant role in the development of the neurodegeneration in order to propose powerful tool for monitoring and treatment of this disease.

Another objective is to evaluate the mechanism of actions of bisindol anti-cancer agents, and to design derivatives without toxic side effects. We have identified a new antimitotic pharmacofor, KAR-2, determined the 3D structure of this drug complexed with its target protein, calmodulin, and evaluated of the mechanism of its action. These data suggested that the anti-calmodulin activity of the bisindols using in chemotherapy could be responsible for the undesired toxic side effects. Our aim is to identify the calmodulin-modulated process(es) the impairment of which is responsible for the toxic side effect of the mother molecule, vinblastine.

SYSTEMS used for our studies are the followings:

CANCER – antimitotic agent – KAR-2: from animal experiments to 3D structure

DESCRIPTION OF THE PROJECTS:

TPPP/p25: a new microtubule-targeting protein

Molecular bases of triosephosphate isomerase deficiency

KAR-2: novel anti-cancer drugs with distinct pharmacology

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 ion sin 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

Research group:

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 Hematology Institute, Budapest (TPI deficient patients)
Prof. Gábor Náray-Szabó ELTE Faculty of Sciences Theoretical Chemistry, Budapest (crystallography)
Dr.György Keseru Gedeon Richter Ltd. (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 (tripszin 4)
Prof. László Pukás Biological Research Center, Laboratory of Functional Genomics (DNA array)
Prof. Viktor Dombrádi University of Debrecen, Department of Medical Chemistry, Debrecen (fphosphorylation)
Prof. Gábor G. Kovács National Phsyatry and neurology Institute, Budapest (immunohistochemistryi)

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Links:

• FP6–2003-LIFESCIHEALTH-I: Bio-Sim

• Spotlight

• Gordon Research Conference on Macromolecular Organization and Cell Function Queen's College, Oxford, U.K. August 15-20, 2004
   
• Encyclopedia of Molecular Medicine, 2001