Molecular pathogenetics

Molecular pathogenetics

RNDr. Gabriela Pavlínková, Ph.D.

RNDr. Gabriela Pavlínková, Ph.D. — Project head

The Institute of Biotechnology of the Czech Academy of Sciences

About us

Using genetically modified mouse models and gene expression profiling, we identify molecular targets for the development of preventive and diagnostic strategies.

This project focuses on

  • transcriptional regulation in neurosensory development and maintenance in the inner ear model
  • the molecular mechanisms involved in pathologies associated with diabetes mellitus
  • the molecular causes of abnormal embryonic development



Research Objectives

  • To identify molecular changes induced by the diabetic exposure.
  • To identify target genes for pathological changes in embryonic development.
  • To identify genes, contributing to developmental defects and heart dysfunctions in diabetic pregnancies.
  • To examine HIF-1α function in molecular responses to diabetes. 

The number of people with diabetes was estimated to be 53 million, or 8.1% of the adult population in Europe in 2011. Both type 1 and type 2 diabetes are associated with a majority of risk health factors, such as hypertension, hyperlipidemia, obesity, thrombosis, autonomic neuropathy, nephropathy, endothelial dysfunction, and microvascular pathology.

Hyperglycemia triggers diabetic tissue damage, including microvascular complications characterized by the increased risk of cardiomyopathy and myocardial infarction, and nephropathy. Hypoxia is another important pathophysiological factor associated with diabetic complications. Transcriptional responses to hypoxia are mediated by hypoxia inducible factor 1 (HIF-1). HIF-1 activates over 800 target genes that are involved in cell proliferation, angiogenesis, glycolytic energy metabolism, and apoptosis. HIF-1 consists of two subunits, the regulatory subunit HIF-1α, and constitutively expressed HIF-1β. Oxygen tension plays a key role in the regulation of HIF-1α expression, stabilization, and activation. The aim of our research is to examine HIF-1α function in molecular responses to diabetes. We are interested in cardiac responses associated with diabetic cardiomyopathy. We are also analyzing the changes induced by the diabetic environment in kidneys resulting in diabetic nephropathy.

Diabetes of mother represents a serious complication for developing embryo. Diabetic pregnancy is associated with an increased incidence of congenital malformations compared with non-diabetic pregnancy. Diabetic embryopathy can affect any developing organ system, although congenital heart defects and neural tube defects are the most frequent malformations in the children of diabetic women. Even without congenital abnormalities, the risk for diabetes and cardiovascular disease is elevated in children and adults who have been exposed to adverse intrauterine conditions. This phenomenon is also termed fetal or developmental programming. However, the molecular mechanisms by which maternal diabetes induces changes in embryos remain unclear. The overarching goal of our research has been to identify key molecular players in changes caused by the exposure to diabetes. Using the mouse as an experimental system and global gene expression profiling, we have identified target genes, which can serve as an indicator for specific abnormalities in heart development and function, and genes, contributing to developmental heart defects in diabetic pregnancies and heart dysfunctions in the adult.

Our second major project focuses on transcriptional regulation in neurosensory embryonic development. Specifically, we are interested in identifying genes and pathways that are crucial in generating specific cell types in the inner ear. This is a critical step for understanding the pathophysiology of hearing disorders, associated with the death of hair cells, supporting cells, neurons and the loss of neuronal contacts. Approximately 71 million Europeans have a hearing impairment. Using mouse model, we analyze the interactions and cooperation of transcription factors, ISLET1, SOX2, and bHLH neurosensory specification factors, in the development of the neuronal and sensory lineages of the inner ear.

Follow us on Twitter: @PavlinkovaLab




Zatecka E, Bohuslavova R, Valaskova E, Margaryan H, Elzeinova F, Kubatova A, Hylmarova S, Peknicova J, Pavlinkova G. The Transgenerational Transmission of the Paternal Type 2 Diabetes-Induced Subfertility Phenotype Front Endocrinol (Lausanne). 2021 Nov 5;12:763863. doi: 10.3389/fendo.2021.763863. eCollection 2021.

Elliott KL, Kersigo J, Lee JH, Jahan I, Pavlinkova G, Fritzsch B, Yamoah EN. Developmental Changes in Peripherin-eGFP Expression in Spiral Ganglion Neurons Front Cell Neurosci. 2021 Jun 15;15:678113. doi: 10.3389/fncel.2021.678113. eCollection 2021.

Bohuslavova R, Smolik O, Malfatti J, Berkova Z, Novakova Z, Saudek F, Pavlinkova G. NEUROD1 Is Required for the Early α and β Endocrine Differentiation in the Pancreas Int J Mol Sci. 2021 Jun 23;22(13):6713. doi: 10.3390/ijms22136713. PMID: 34201511

Elliott KL, Pavlinkova G, Chizhikov VV, Yamoah EN, Fritzsch B. Neurog1, Neurod1, and Atoh1 are essential for spiral ganglia, cochlear nuclei, and cochlear hair cell development Fac Rev. 2021 May 11;10:47. doi: 10.12703/r/10-47. eCollection 2021.

Chumak T, Tothova D, Filova I, Bures Z, Popelar J, Pavlinkova G, Syka J. Overexpression of Isl1 under the Pax2 Promoter, Leads to Impaired Sound Processing and Increased Inhibition in the Inferior Colliculus Int J Mol Sci. 2021 Apr 26;22(9):4507. doi: 10.3390/ijms22094507.

Elliott KL, Pavlínková G, Chizhikov VV, Yamoah EN, Fritzsch B. Development in the Mammalian Auditory System Depends on Transcription Factors Int J Mol Sci. 2021 Apr 18;22(8):4189. doi: 10.3390/ijms22084189.


Pavlinkova G. Molecular Aspects of the Development and Function of Auditory Neurons Int J Mol Sci. 2020 Dec 24;22(1):131. doi: 10.3390/ijms22010131.

Filova I, Dvorakova M, Bohuslavova R, Pavlinek A, Elliott KL, Vochyanova S, Fritzsch B, Pavlinkova G. Combined Atoh1 and Neurod1 Deletion Reveals Autonomous Growth of Auditory Nerve Fibers Mol Neurobiol. 2020 Dec;57(12):5307-5323. doi: 10.1007/s12035-020-02092-0. Epub 2020 Sep 3.

Hylmarova S, Stechova K, Pavlinkova G, Peknicova J, Macek M, Kvapil M. The impact of type 1 diabetes mellitus on male sexual functions and sex hormone levels. Endocr J. 2020 Oct 16. doi: 10.1507/endocrj.EJ19-0280.

Dvorakova M, Macova I, Bohuslavova R, Anderova M, Fritzsch B, Pavlinkova G. Early ear neuronal development, but not olfactory or lens development, can proceed without SOX2. Dev Biol. 2020 Jan 1;457(1):43-56. doi: 10.1016/j.ydbio.2019.09.003. Epub 2019 Sep 14.


Romana Bohuslavova, Radka Cerychova, Frantisek Papousek, Veronika Olejnickova, Martin Bartos, Agnes Görlach, Frantisek Kolar, David Sedmera, Gregg L. Semenza, and Gabriela Pavlinkova. HIF-1α is required for development of the sympathetic nervous system. Proc Natl Acad Sci U S A. 2019 Jun 13. pii: 201903510. doi: 10.1073/pnas.1903510116.

Fritzsch B, Elliott KL, Pavlinkova G, Duncan JS, Hansen MR, Kersigo JM. Neuronal Migration Generates New Populations of Neurons That Develop Unique Connections, Physiological Properties and Pathologies. Front Cell Dev Biol. 2019 Apr 24;7:59. doi: 10.3389/fcell.2019.00059. eCollection 2019. Review.

Fritzsch B, Elliott KL, Pavlinkova G. Primary sensory map formations reflect unique needs and molecular cues specific to each sensory system. F1000Res. 2019 Mar 27;8. pii: F1000 Faculty Rev-345. doi: 10.12688/f1000research.17717.1. eCollection 2019. Review.


Macova I, Pysanenko K, Chumak T, Dvorakova M, Bohuslavova R, Syka J, Fritzsch B, Pavlinkova G. Neurod1 is essential for the primary tonotopic organization and related auditory information processing in the midbrain. J Neurosci. 2018 Dec 12. pii: 2557-18. doi: 10.1523/JNEUROSCI.2557-18.2018.

Cerychova R, Bohuslavova R, Papousek F, Sedmera D, Abaffy P, Benes V, Kolar F, Pavlinkova G. Adverse effects of Hif1a mutation and maternal diabetes on the offspring heart. Cardiovasc Diabetol. 2018 May 12;17(1):68. doi: 10.1186/s12933-018-0713-0.

Cerychova R, Pavlinkova G. HIF-1, Metabolism, and Diabetes in the Embryonic and Adult Heart. Front Endocrinol (Lausanne). 2018 Aug 15;9:460. doi: 10.3389/fendo.2018.00460. eCollection 2018. Review.


Bohuslavova, R., Cerychova, R., Nepomucka, K., Pavlinkova, G. Renal injury is accelerated by global hypoxia-inducible factor 1 alpha deficiency in a mouse model of STZ-induced diabetes. BMC Endocrine Disorders, 17: 48, 2017. doi: 10.1186/s12902-017-0200-8. ISSN: 1472-6823.

Bohuslavova, R., Dodd, N., Macova, I., Chumak, T., Horak, M., Syka, J., Fritzsch, B., Pavlinkova, G. Pax2-Islet1 Transgenic Mice Are Hyperactive and Have Altered Cerebellar Foliation. Molecular Neurobiology, 54(2): 1352-1368, 2017. doi: 10.1007/s12035-016-9716-6. ISSN 0893-7648.

Pavlinkova, G., Margaryan, H., Zatecka, E., Valaskova, E., Elzeinova, F., Kubatova, A., Bohuslavova, R., Peknicova, J. Transgenerational inheritance of susceptibility to diabetes-induced male subfertility. Scientific Reports, 7: 4940, 2017. doi: 10.1038/s41598-017-05286-0. ISSN: 2045-2322.


Dvorakova, M., Jahan, I., Macova, I., Chumak, T., Bohuslavova, R., Syka, J., Fritzsch, B., Pavlinkova, G. Incomplete and delayed Sox2 deletion defines residual ear neurosensory development and maintenance. Scientific Reports, 6: 38253, 2016. doi: 10.1038/srep38253. ISSN 2045-2322.

Chumak, T., Bohuslavova, R., Macova, I., Dodd, N., Buckiova, D., Fritzsch, B., Syka, J., Pavlinkova, G. Deterioration of the Medial Olivocochlear Efferent System Accelerates Age-Related Hearing Loss in Pax2-Isl1 Transgenic Mice. Molecular Neurobiology, 53(4): 2368-2383, 2016. doi: 10.1007/s12035-015-9215-1. ISSN 0893-7648.


Bohuslavova, R., Skvorova, L., Cerychova, R., Pavlinkova, G. Gene expression profiling of changes induced by maternal diabetes in the embryonic heart. Reproductive Toxicology, 57: 147-156, 2015. doi: 10.1016/j.reprotox.2015.06.045. ISSN 0890-6238.

Ornoy, A., Reece, E. A., Pavlinkova, G., Kappen, C., Miller, R. K. Effect of maternal diabetes on the embryo, fetus, and children: Congenital anomalies, genetic and epigenetic changes and developmental outcomes. Birth Defects Research Part C: Embryo Today, 105(1): 53-72, 2015. doi: 10.1002/bdrc.21090. eISSN 1542-9768.


Bohuslavova, R., Kolar, F., Sedmera, D., Skvorova, L., Papousek, F., Neckar, J., Pavlinkova, G. Partial deficiency of HIF-1α stimulates pathological cardiac changes in streptozotocin-induced diabetic mice. BMC Endocrine Disorders, 14:11, 2014. doi: 10.1186/1472-6823-14-11. ISSN 1472-6823.


Bohuslavova, R., Skvorova, L., Sedmera, D., Semenza, G. L., Pavlinkova, G. Increased susceptibility of HIF-1α heterozygous-null mice to cardiovascular malformations associated with maternal diabetes. Journal of Molecular and Cellular Cardiology, 60C:129-141, 2013. ISSN 0022-2828.


Salbaum JM, Kruger C, Zhang X, Delahaye NA, Pavlinkova G, Burk DH, Kappen C. Altered gene expression and spongiotrophoblast differentiation in placenta from a mouse model of diabetes in pregnancy. Diabetologia. 2011; 54(7):1909-20.


Bohuslavova R, Kolár F, Kuthanova L, Neckar J, Tichopad A, Pavlinkova G. Gene expression profiling of gender differences in HIF1-dependent adaptive cardiac responses to chronic hypoxia. J Appl Physiol. 2010 Oct;109(4):1195-202.


Pavlinkova, G; Salbaum, JM; Kappen, C. Maternal Diabetes alters Transcriptional Programs in the Developing Embryo. BMC Genomics 2009, 10:274.