Željko M. Svedružić Ph.D., Curriculum Vitae, July, 15th, 2013
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Željko M. Svedružić, Ph.D.
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Assistant Professor at
Department of Biotechnology
and Adjunct Faculty at
the Faculty of Medicine
University of Rijeka, Croatia
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Office: 8th floor, Rm. 823.
Radmile Matejčić 2
Campus Trsat
51000 Rijeka, Croatia
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Email:
zsvedruz-at-biol.pmf.hr
zeljko.svedruzic-at-uniri.hr
zeljko.svedruzic-at-med.kuleuven.be
zeljko-at-wsu.edu
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Tel. +385-51-584-575;
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personal web page:
https://profiles.google.com/10672051580
9875304148#106720515809875304148/
about
Research: 1.
Development
of
mechanism-based
inhibitors
of
mammalian/human
DNA
methyltransferases with IC50 values below 50 nM. The most successful inhibitors can
be used for control of functional organization of mammalian genome in research
laboratories, biotechnology, and ultimately in clinics for treatment of pathogenic
mechanisms related to epigenetic processes (i.e. tissue regeneration, oncogenesis,
psychiatric and neurological disorders, viral infections, immunological disorders).
2. Development of novel bivalent mechanism-based inhibitors of membrane-embedded
protease -secretase. The most successful compounds can be used for treatment and
early-diagnosis of Alzheimer’s disease, or for control of different physiological
processes that depend on cell-to-cell communication.
Specialty: Enzymology: in vitro, in vivo and in silico approaches for studies of structure and function
of biomolecules.
Training: biochemistry, physical biochemistry (i.e. biophysics), medicinal chemistry, bioorganic
chemistry, molecular genetics, biological membranes, medical biochemistry, cell biology.
Expertise: molecular mechanisms in epigenetics and chromatin organization; molecular mechanisms
in Alzheimer’s disease; protein-protein and protein-ligand interactions; assay-development
and drug-design based on enzyme structure-function principles; substrate channeling.
Teaching: on ongoing basis: molecular modeling and numerical methods in biomedical sciences, i.e.
structure and function of biomolecules, enzyme kinetics, and protein-ligand interactions.
Mentoring individual students in research and thesis preparation. Invited lectures:
molecular mechanisms in Alzheimer’s disease or molecular mechanisms in epigenetics.
Major accomplishments: 1) DNA methyltransferases: enzymatic mechanism, regulation, and novel
drug-design strategies. 2) membrane-embedded protease -secretase: enzymatic
mechanism, regulation and novel drug-design and early diagnostic strategies for
Alzheimer’s disease. 3) substrate channeling in transient protein-protein interactions.
Career goals: development and commercialization of inhibitors and modulators of human DNA
methyltransferase Dnmt1 and membrane embedded protease -secretase.
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Željko M. Svedružić Ph.D., Curriculum Vitae, July, 15th, 2013
Essential information in the reverse chronological order:
2013 to present: assistant professor at Department of Biotechnology and adjunct faculty at the
Faculty of Medicine University of Rijeka, Croatia.
2010 to 2013: laboratory for medical biochemistry at the University Psychiatric hospital Rab and
adjunct faculty at the Faculty of Medicine, University of Rijeka, Croatia.
Senior Scientist Appointments:
2007 to 2010, joint appointment at: i) the Faculty of Medicine, KU Leuven, Belgium and; ii)
Neurodegenerative Diseases Drug Hunting Team, Eli Lilly Pharmaceutical Company. Project:
Molecular pathophysiology of Alzheimer’s disease and inhibitors of intramembrane protease γsecretase. Project Leaders: Professor Bart de Strooper (KUL) and Dr. Eric Karran (Eli Lilly, UK
and USA).
2003 to 2006; Department of Biochemistry and Biophysics, Washington State University, USA.
Project: DNA damage induced changes in DNA flexibility and DNA-nucleosome interaction.
DNA repair in nuclear extracts. Project leader: Regents Professor Michael J. Smerdon.
Postdoctoral Research:
2002 and 1998-2000; Department of Chemistry, University of California, Santa Barbara in
collaboration with a biopharmaceutical start-up company Epigenx. Project: Enzymology and
inhibitors of mammalian and bacterial cytosine DNA methyltransferases. Project leader:
Professor Norbert O. Reich.
2001. Department of Biochemistry, Duke University Medical Center, USA. Project: Enzymology of
protein phosphatase CDC25B with Cdk2/CycA protein complex as the substrate (Cdk2= cycline
dependent kinase 2; CycA= cyclin A). Project leader: Assistant Professor Johannes Rudolph.
Education and Personal Information:
1993-1998, Ph.D. student at Department of Biochemistry, Oklahoma State University, USA. Thesis
title: “Substrate Channeling between NAD(H) Dehydrogenases: Enzyme Kinetics, ProteinProtein Interaction, and Molecular Modeling Studies”. Mentor: Professor H. Olin Spivey
(deceased).
1992-1993, Diploma thesis at Max-Planck Institut für Biochemie, Martinsried Bei München,
Germany. Thesis title: “Purification of p17 protein; a component of Actin-Myosin complex from
Dictyostelium discoideum”. Mentor: Günther Gerisch, professor and department head.
1988-1992, undergraduate student at the Faculty of Science and Mathematics, University of
Zagreb, Croatia.
1987-1988, compulsory military service
1987 High School degree: technician for electronic devices
Miscellaneous:
1. Ad hoc reviewer: DNA Repair, Elsevier Ltd; Epigenetics, Landes Bioscience; Biochemical Journal;
Bioorganic & Medicinal Chemistry. Letters, Elsevier Ltd.; Journal of Neuroscience; Biochimie
Elsevier Ltd; Current Medicinal Chemistry; BBA - Proteins and Proteomics; WMC Biochemistry
Faculty.
2. Conferences: about 20 years of active participation in professional meetings and conferences.
3. Teaching: about 20 years of direct and indirect mentoring of junior colleagues in research
laboratories.
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Željko M. Svedružić Ph.D., Curriculum Vitae, July, 15th, 2013
Publications
(* corresponding author):
1. Svedružić Ž. M.*, Popović K, Šendula-Jengić V. Modulators of γ-secretase activity can facilitate the
toxic side-effects and pathogenesis of Alzheimer’s disease. PLoS One, January 7th 2013.
(http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0050759)
2. Svedružić Ž. M.* Popović K, Smoljan I, Šendula-Jengić V. Modulation of γ-secretase activity by
multiple enzyme-substrate interactions: Implications in pathogenesis of Alzheimer’s disease. PLoS
One, April 2012.
(http://dx.plos.org/10.1371/journal.pone.0032293).
3. Svedružić Ž. M.*, book chapter titled: Mammalian DNA methyltransferase Dnmt1: Structure and
Function. Book title: Modification of Mammalian DNA: Mechanism, Management, Missions, and
Medical Implications. Elsevier Series titled: Progress in Molecular Biology and Translational Science.
2011;101:221-54.
(http://www.bolnicarab.hr/upload/Svedruzic/Ch06_svedruzic_book_complete_2011.pdf)
4. Svedružić Ž. M.* Mammalian Cytosine DNA methyltransferase Dnmt1: Enzymatic Mechanism,
Novel Mechanism-Based Inhibitors, and RNA-directed DNA methylation. Curr. Med. Chem., 15(1):
92-106; (2008).
(http://www.bolnicarab.hr/upload/Svedruzic/referenca%204.pdf)
5. Svedružić Ž. M., Wang C., Kosmoski J.V. and Smerdon M.J*. Accommodation and Repair of a UV
Photoproduct in DNA at Different Rotational Settings on the Nucleosome Surface. J. Biol. Chem.,
280(48): 40051-40057; 2005.
(http://www.ncbi.nlm.nih.gov/pubmed/16210312)
6. Svedružić Ž. M. and N.O. Reich*. The Mechanism of Allosteric Regulation of Dnmt1’s
Processivity. Biochemistry, 14972-14988; 44(45); 2005.
(http://www.bolnicarab.hr/upload/Svedruzic/referenca%206.pdf)
7. Svedružić Ž. M. and N.O. Reich*. DNA Cytosine C5 Methyltransferase Dnmt1: Catalysis Dependent
Release of Allosteric Inhibition. Biochemistry, 9472-9485; 44(27); (2005).
(http://www.bolnicarab.hr/upload/Svedruzic/referenca%206.pdf)
8. Svedružić Ž. M. and N.O. Reich*. The Mechanism of Target Base Attack in DNA Cytosine C5
Methylation. Biochemistry, 11460-11473; 43(36); (2004).
(http://www.bolnicarab.hr/upload/Svedruzic/referenca%206.pdf)
9. Svedružić Ž. M.* and H. O. Spivey. Interaction between Mammalian Glyceraldehyde-3-phosphate
Dehydrogenase and L-Lactate Dehydrogenase from Heart and Muscle. Proteins, Structure, Function
and Bioinformatics, 63:501-511; (2006).
(http://www.bolnicarab.hr/upload/Svedruzic/referenca9.pdf)
10. Lehoux E. A., Svedružić Ž., and Spivey, H. O*. Determination of Specific Radioactivity of [14C]
Lactate by Enzymatic Decarboxylation and CO2 Collection. Anal. Biochemistry, 190-195 (1997).
In preparation: (* corresponding author):
P1. Svedružić Ž. M.* Popović K, Šendula-Jengić V. Shared pathogenic mechanism in sporadic and
different familiar cases of Alzheimer’s disease: implications in early diagnosis of the disease.
P2. Svedružić Ž. M.* Full insilico optimization of the first DNA-independent mechanism-based
inhibitor of the mammalian DNA methyltransferase Dnmt1.
P3. Svedružić Ž. M.* Substrate-lock mechanism controls de novo methylation by mammalian DNA
methyltransferase Dnmt1.
P4. Svedružić Ž. M.*, Popović K., Šendula-Jengić V. The basic enzymology of modulation of γsecretase activity: identification of the key pharmacophoric groups.
P5. Svedružić Ž. M.*, Svedružić D., Spivey H.O. Allosteric Regulation of Substrate Channeling in
Transient Protein-Protein Interactions; the case of NAD(H) dehydrogenases.
P6. Svedružić Ž. M.* A flexible loop and two charged amino acids regulate formation and break-up of
transient catalytic complex between protein phosphatase CDC25B and Cdk2/Cycline-A
heterodimer.
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