Profile

Education

1997 – 2004: graduate studies at Faculty of Natural Sciences, Charles University in Prague, Czech Republic (PhD in molecular biology, genetics and virology)
1992 - 1997: undergraduate studies at Faculty of Natural Sciences, Charles University in Prague (MSc in molecular biology, genetics and virology)

Chronology of Employment

2007-present: Institute of Organic Chemistry and Biochemistry CAS, senior group leader
2022-present: Institute of Organic Chemistry and Biochemistry CAS, vice director for research
2007-2021: Institute of Molecular Genetics CAS in Prague, senior group leader
2005–2007:  UT Southwestern Medical Center, Department of Biochemistry, Dallas, TX, U.S.A, with Prof.  Z. Otwinowski, postdoctoral fellow
1997 – 2005: Institute of Molecular Genetics AS CR, Prague, Czech Republic, research fellow

Teaching experience

2019 – present: associate professor of Biophysics at University of South Bohemia
2003 – 2004, 2007-present: Faculty of Natural Sciences, Charles University in Prague, Department of Biochemistry, semestral course Determination of 3-D structures of macromolecules
2001, 2002, 2003, 2005: University and Academic Center Nové Hrady, Czech Republic, Organizing and teaching at practical courses Crystallization course
2004, 2006, 2008, 2010, 2012, 2014, 2016, 2018, 2021: University and Academic Center Nové Hrady, Czech Republic, Organizing and teaching at FEBS practical courses: Advanced methods in protein crystallization
2005, 2009, 2011, 2017, 2019: University of Granada, Spain, Teaching at International School on Biological Crystallization

Membership in Scientific Societies and Professional Associations

Czech and Slovak Crystallographic Association (Member of Board since 2016, vise-president since 2022)
Member of European Crystallographic Association
Member of Czech Society for Biochemistry and Molecular Biology
Member of Czech Society for Structural Biology
Member of International Organization for Biological Crystallization

Scientific Community Activities

Member of Board of Institute of Organic Chemistry and Biochemistry CAS (2017-now)
Member of Board of Institute of Molecular Genetics CAS (2012-2017)
Member of Board of Faculty of Tropical Agrisciences, Czech University of Life Sciences (since 2018)
Member of Heart of Europe bio-Crystallography Meeting Committee (2018-now, since 2020 chair)
Selection Panel of Helmholtz Centrum Berlin (2016-2021, 2018-2021 chair)
Organizer of FEBS practical courses: Advanced methods in protein crystallization
Organizer International conference on crystallization of biological macromolecules, 2016
Organizer of World Congress of International Union of Crystallography, Prague, 2021

Research interests and activities

structural biology, structure-aided design of enzyme inhibitors, structure of prokaryotic transcriptional
repressors, protein crystallization methods

Selected papers

Sulfonamido carboranes as highly selective inhibitors of cancer-specific carbonic anhydrase IX
Sulfonamido carboranes as highly selective inhibitors of cancer-specific carbonic anhydrase IX
European Journal of Medicinal Chemistry 200: 112460 (2020)
Carbonic anhydrase IX (CA IX) is a transmembrane enzyme overexpressed in hypoxic tumors, where it plays an important role in tumor progression. Specific CA IX inhibitors potentially could serve as anti-cancer drugs. We designed a series of sulfonamide inhibitors containing carborane clusters based on prior structural knowledge of carborane binding into the enzyme active site. Two types of carborane clusters, 12-vertex dicarba-closo-dodecaborane and 11-vertex 7,8-dicarba-nido-undecaborate (dicarbollide), were connected to a sulfonamide moiety via aliphatic linkers of varying lengths (1–4 carbon atoms; n = 1–4). In vitro testing of CA inhibitory potencies revealed that the optimal linker length for selective inhibition of CA IX was n = 3. A 1-sulfamidopropyl-1,2-dicarba-closo-dodecaborane (3) emerged as the strongest CA IX inhibitor from this series, with a Ki value of 0.5 nM and roughly 1230-fold selectivity towards CA IX over CA II. X-ray studies of 3 yielded structural insights into…

Latest publications

Structural characterization of two prototypical repressors of SorC family reveals tetrameric assemblies on DNA and mechanism of function
Nucleic Acids Research 2024: Early View
Characterization of new highly selective pyrazolo[4,3-d]pyrimidine inhibitor of CDK7
Biomedicine & Pharmacotherapy 161: 114492 (2023)
An evolutionary molecular adaptation of an unusual stefin from the liver fluke Fasciola hepatica redefines the cystatin superfamily
Journal of Biological Chemistry 299 (3): 102970 (2023)