Modeling induced pluripotent stem cells (iPSCs) to improve understanding of pathomechanisms underlying cardiac electrical disorders in Kazakh patients
Project goal: To establish an experimental model of a known pathogenic mutation of the hRYR2 gene associated with primary electrical disorder of the heart: a human stem cell-derived cardiomyocyte cell model and to conduct functional studies
Project description: Primary electrical disorders (PEDs) of the heart, or channelopathies, are genetically determined diseases predisposing to sudden cardiac death (SCD) caused by ventricular tachyarrhythmias (VT). In this project, we will establish an experimental model of a known pathogenic hRYR2 mutation associated with cardiac electrical disease: a human stem cell-derived cardiomyocyte cell model and conduct functional studies. Functional characterization and validation of this model using innovative imaging and electrophysiology methods will allow us to assess the impact of the mutation at the cellular level, proving its contribution to the etiology of the disease. In addition, after validation of this model, we will apply this strategy to functionally assess the pathogenicity of a genetic variant of unclear significance (VUS) detected in Kazakhstani patients with arrhythmia using the established model. By establishing the use of this model to predict the pathogenicity of PED-associated VUS, more accurate risk stratification and the skillful use of tailored prevention strategies may be possible in the future, potentially also for other cardiac diseases.
Project facilitators: PI: Saule Rakhimova, Ainur Akilzhanova, Diana Samatkyzy, Madina Zhalbinova, Ayaulym Chamoieva, Nazerke Satvaldina
Realisation period: 2023-2025
Expected results: For the first time in the Republic of Kazakhstan, a model of cardiomyocytes obtained from induced pluripotent stem cells (iPSCs) will be created for the known pathogenic mutation hRYR2 associated with primary electrical heart disease.
This model will be functionally characterized and validated using innovative imaging and electrophysiology methods, the impact of the mutation at the cellular level will be assessed, and its contribution to the etiology of the disease will be proven.
A functional assessment of the pathogenicity of genetic variants of unclear significance (VUS) identified in Kazakhstani patients with arrhythmia will be carried out using the created model. The research results will be published in the form of articles in foreign peer-reviewed scientific journals in accordance with the requirements of the TD:
For branches in the field of natural sciences:
for fundamental research:
- at least 3 (three) articles and (or) reviews in peer-reviewed scientific publications in the scientific direction of the project, indexed in the Science Citation Index Expanded and included in the 1st (first), 2nd (second) and (or) 3rd (third) quartile by impact factor in the Web of Science database and (or) having a percentile by CiteScore in the Scopus database of at least 50 (fifty);
- at least 1 (one) article or review in a peer-reviewed foreign or domestic publication recommended by the CQASE ME RK;
- either at least 2 (two) articles and/or reviews in peer-reviewed scientific publications indexed in Science Citation Index Expanded and included in the 1st (first) and/or 2nd (second) quartiles by impact factor in the Web of Science database and/or having a CiteScore percentile in the Scopus database of at least 65 (sixty-five);
- either at least 1 (one) article or review in a peer-reviewed scientific publication indexed in Science Citation Index Expanded and included in the 1st (first) quartile in the Web of Science database or having a CiteScore percentile in the Scopus database of at least 95 (ninety-five).
Methodology: Recruitment of study participants, generation of iPSCs and cardiomyocyte differentiation, functional studies, immunostaining, genomic sequencing, gene expression analysis, statistical analysis
Contacts: saule.rakhimova@nu.edu.kz
Project goal: To establish an experimental model of a known pathogenic mutation of the hRYR2 gene associated with primary electrical disorder of the heart: a human stem cell-derived cardiomyocyte cell model and to conduct functional studies
Project description: Primary electrical disorders (PEDs) of the heart, or channelopathies, are genetically determined diseases predisposing to sudden cardiac death (SCD) caused by ventricular tachyarrhythmias (VT). In this project, we will establish an experimental model of a known pathogenic hRYR2 mutation associated with cardiac electrical disease: a human stem cell-derived cardiomyocyte cell model and conduct functional studies. Functional characterization and validation of this model using innovative imaging and electrophysiology methods will allow us to assess the impact of the mutation at the cellular level, proving its contribution to the etiology of the disease. In addition, after validation of this model, we will apply this strategy to functionally assess the pathogenicity of a genetic variant of unclear significance (VUS) detected in Kazakhstani patients with arrhythmia using the established model. By establishing the use of this model to predict the pathogenicity of PED-associated VUS, more accurate risk stratification and the skillful use of tailored prevention strategies may be possible in the future, potentially also for other cardiac diseases.
Project facilitators: PI: Saule Rakhimova, Ainur Akilzhanova, Diana Samatkyzy, Madina Zhalbinova, Ayaulym Chamoieva, Nazerke Satvaldina
Realisation period: 2023-2025
Expected results: For the first time in the Republic of Kazakhstan, a model of cardiomyocytes obtained from induced pluripotent stem cells (iPSCs) will be created for the known pathogenic mutation hRYR2 associated with primary electrical heart disease.
This model will be functionally characterized and validated using innovative imaging and electrophysiology methods, the impact of the mutation at the cellular level will be assessed, and its contribution to the etiology of the disease will be proven.
A functional assessment of the pathogenicity of genetic variants of unclear significance (VUS) identified in Kazakhstani patients with arrhythmia will be carried out using the created model. The research results will be published in the form of articles in foreign peer-reviewed scientific journals in accordance with the requirements of the TD:
For branches in the field of natural sciences:
for fundamental research:
- at least 3 (three) articles and (or) reviews in peer-reviewed scientific publications in the scientific direction of the project, indexed in the Science Citation Index Expanded and included in the 1st (first), 2nd (second) and (or) 3rd (third) quartile by impact factor in the Web of Science database and (or) having a percentile by CiteScore in the Scopus database of at least 50 (fifty);
- at least 1 (one) article or review in a peer-reviewed foreign or domestic publication recommended by the CQASE ME RK;
- either at least 2 (two) articles and/or reviews in peer-reviewed scientific publications indexed in Science Citation Index Expanded and included in the 1st (first) and/or 2nd (second) quartiles by impact factor in the Web of Science database and/or having a CiteScore percentile in the Scopus database of at least 65 (sixty-five);
- either at least 1 (one) article or review in a peer-reviewed scientific publication indexed in Science Citation Index Expanded and included in the 1st (first) quartile in the Web of Science database or having a CiteScore percentile in the Scopus database of at least 95 (ninety-five).
Methodology: Recruitment of study participants, generation of iPSCs and cardiomyocyte differentiation, functional studies, immunostaining, genomic sequencing, gene expression analysis, statistical analysis
Contacts: saule.rakhimova@nu.edu.kz