Transcription regulation in embryonal development and the pathogenesis of disease
Laboratory of Molecular Pathogenetics
Group leader: RNDr. Gabriela Pavlínková, Ph.D., DSc.
Our research program is focused on transcriptional regulation during embryonic development, the molecular mechanisms of developmental programming, and identification of the molecular causes of abnormal embryonic development and disease predispositions. We are particularly interested in HIF-1, ISL1, SOX2, and NEUROD1 transcription factor networks and how their dysfunction affects embryonic development and can increase pre-dispositions of an individual to diseases such as diabetes, heart disease or hearing loss. We are also analyzing the combinatorial effects of the environment (e.g. diabetes) and genetic mutations. Using mouse models, and single cell and bulk transcriptome analyses, we are studying molecular mechanisms to identify targets for the development of preventive and diagnostic strategies.
About 422 million people worldwide have diabetes. Diabetes is a metabolic disease that involves the death or dysfunction of the insulin-secreting beta cells in the pancreas. Understanding how developmental and environmental cues shape cellular identity and contribute to the manifestation of pancreatic diseases, could have valuable implications for treatment strategies.
Diabetes is associated with a majority of risk health factors, such as hypertension, heart disease, obesity, autonomic neuropathy, nephropathy, and microvascular pathology. Hypoxia is another important pathophysiological factor associated with diabetic complications. Transcriptional responses to hypoxia are mediated by hypoxia inducible factor 1 (HIF-1). The aim of our research is to examine HIF-1 function in diabetes and heart disease.
Diabetes of the mother represents a serious complication for the developing embryo with an increased incidence of congenital malformations. Even without congenital abnormalities, the risk for diabetes and cardiovascular disease is elevated in offspring exposed to adverse intrauterine conditions. This phenomenon is also termed fetal or developmental programming. The overarching goal of our research is to identify the key molecular players in changes caused by the exposure to diabetes.
Approximately 71 million Europeans have a hearing impairment. Ageing societies face a global pandemic of around 900 million hearing impaired people by 2050. Neurosensory hearing loss is permanent and results from the death of neurons or sensory cells, which have little ability to regenerate. Although cochlear implants can restore some hearing, regenerating lost neurosensory cells and to delay or even prevent the onset of hearing loss are the most important targets for the immediate future. Our overreaching goal is to understand the molecular interactions necessary for neurosensory development and maintenance and to use this knowledge as a basis for new therapeutic strategies.
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