Laboratory of biochemistry and cell biology of inherited errors of metabolism

 Head of laboratory: 

Jana Ledvinová, PhD.

Laboratory members:

Befekadu Asfaw, Ph.D. assoc. prof. Marie Hubálek-Kalbáčová, Ph.D.
Linda Berná, Ph.D. Jan Lukáš, Ph.D.
Robert Dobrovolný, Ph.D. Jitka Honzíková, MSc.
Martin Hřebíček, MD, Ph.D. Jitka Rybová, MSc.
Ladislav Kuchař, Ph.D. Dita Mušálková, MSc.
Filip Majer, Ph.D. Helena Poupětová, MSc.
Lenka Steiner Mrázová, Ph.D Antonín Brož, MSc.
Eva Richtrová, Ph.D. Martina Verdánová, MSc.
Jakub Sikora, MD, Ph.D. Blanka Bílková

Michaela Fialová 

Research Group of Lysosomal Storage Disorders

Group leaders: Jana Ledvinová, Ph.D., Martin Hřebíček, MD, Ph.D.

The group has a long-term interest in molecular genetics and biochemistry of inherited metabolic disorders, with an emphasis on lysosomal storage disorders (LSDs). Our studies have been focused on catabolism of sphingolipids (e.g. Fabry, Gaucher, Niemann-Pick diseases, metachromatic leukodystrophy (MLD), GM1 and GM2 gangliosidoses and deficits of sphingolipid hydrolase activators), glycosaminoglycans (mucopolysaccharidosis Type III C), and defects of non-enzymatic lysosomal proteins (Nemann-Pick type C disease (NPC), Danon disease). We have recently characterized promoter of HGSNAT, the gene mutated in mucopolysaccharidosis Type III C and alternative promoter of the gene encoding glucocerebrosidase, which is deficient in Gaucher disease.

We have characterized the relationship between X-inactivation and the severity of the disease in Fabry heterozygotes. For further studies we have developed a innovative technique for measurement of X-inactivation skewing from genomic DNA, which examines several loci and is informative in much greater proportion of females than the most commonly used HUMARA method.

We are currently involved in complex biochemical, morphological and molecular characterization of Czech patients with Niemann-Pick type C disease and development of a novel biochemical diagnostic method for NPC.

Another of our research interests relate to preparation of iPS-based cell models of some LSDs for the study of biology and development of therapies for these diseases. Fabry disease cell model is used to study contributions of two related glycohydrolases, lysosomal alpha-galactosidase A and alpha-N-acetylglactosaminidase, to the degradation of glycolipid antigens of blood group B. Novel lipidomic tests were developed (published study of sulphatides in MLD). Techniques commonly used in the laboratory include functional tests in cell cultures, molecular biology techniques, advanced microscopic techniques and tandem mass-spectrometry for lipidomic analyses.

Research Group of Cell Interaction with Nanomaterials

Group leader: assoc. prof. Marie Hubálek-Kalbáčová, Ph.D.

Laboratory of cell interaction with nanomaterials is concerned with basic and applied research in the field of human cell interaction with nanomaterials used in medicine (orthopaedics, stomatology, drug delivery, etc.) and bioelectronics.

The basic area of our research is the interaction of human osteoblasts and mesenchymal stem cells with variously structured and terminated nanocrystalline diamond surfaces, with surfaces based on carbon and titanium nanotubes, with surface of differently prepared graphene and many other materials. Material biocompatibility is studied by wide range of biochemical methods. Intrinsic interactions are observed by fluorescently stained cellular proteins and organelles (immunological staining or GFP transformed cell lines) with confocal microscopy in incubation well enabling real time visualization under physiological conditions. The comparison of expression profiles of cells on different substrates is a prerequisite for further selection of the most suitable substrate surface for cell proliferation and differentiation. Established methods can be universally used for study of any solid substrate or nanoparticles interaction with cells. In the field of nanoparticles cytotoxicity, entry of silicon nanocrystals and nanocrystalline diamond particles into cells as well as their cell compartment distribution is studied as well.

In the field of bioelectronics, the group is cooperating on the development and application of cell transistor on the basis of nanodiamonds or carbon nanotubes. Most of the used materials are conductors or semi-conductors, thus the electrical stimulation of the cells or electrical measurement of cell processes can be monitored.

Grant support:


IGA MZ (2009-2011)

Biochemistry and Cell Biology of Human Acetyl-Coenzyme A: Alpha-Glucosaminide N-Acetyltransferase – Basis for Future Therapeutic Applications in Mucopolysaccharidosis type IIIC


IGA MZ (2011-2015)

Niemann-Pick disease type C: clinical, molecular genetic, biochemical and morphological study. Development of new diagnostic and predictive algorithms


MŠMT (2009-2010)

Phenotype-genotype relations in lysosomal storage diseases related to beta-galactosidase deficiency


IGA MZ (2013-2015)

Progress in methods of laboratory diagnostics of inherited lysosomal neurodegenerative disorders


EAHC (2013-2015)

The International Niemann-Pick Disease Registry

LH14246 *

MŠMT (2014-2016)

Doped silicon nanocrystals – novel nanomaterials for photonics and bio-applications

Projects marked with an * are carried out in collaboration with main investigators from other institutions.