V.E.J. (Victoria) Palasantzas
PhD Candidate
E-mail:
v.e.j.palasantzas umcg.nl
Expertise
Expertise in Biomedische wetenschappen, stofwisseling, celbiologie en moleculaire laboratorium technieken inclusief 3D en microfluidic (chip) cel cultuur.
PhD project description: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease, affecting nearly one-third of the global population. To study NAFLD, current experimental models e.g., animals and 2D cell cultures, pose various limitations including species-specific differences and lack of complexity.
To overcome these limitations, I aim to engage the innovative, human-based organ-on-a-chip system. At this moment, there are no approved pharmacological interventions for NAFLD. Alternatively, lifestyle interventions are deemed unsustainable now, but these could become an attractive option if provided with a molecular basis for nutriceuticals. Interestingly, short-chain fatty acids (SCFAs), fermentation products of our intestinal microbiota from dietary fiber rs, could provide such basis as they attenuate fatty liver disease both in animal models as well as clinical studies.
Here, I aim to establish the underlying mechanisms of their effects to provide novel strategies in the prevention or treatment of NAFLD.To achieve this, I have defined three sub-objectives:
1. Understanding the biological effects of SCFAs on the liver using NAFLD on-a-chip. By co-culturing hepatocytes with Kupffer cells followed by lipotoxic stimulation with free fatty acids and TNFα, steatohepatitis is triggered. Relevant steatohepatitis-related physiological readouts will be assessed. Thereafter, I wish to characterize the fatty vs. inflammatory (NASH) phenotype of NAFLD by physiological readouts.
2. Establishing the molecular mechanisms underlying the effects of SCFAs on NAFLD. To explore the complete differential profile of SCFAs in NAFLD, we will employ various omics analyses including RNA-sequencing, proteomics and lipidomics.
3. Investigating downstream molecular pathways by using CRISPR/Cas9 gene-editing approaches on candidate genes identified in objective 2 and utilizing tools at hand by mydepartments in with the UMCG iPSC/CRISPR facility.
To summarize, I expect to gain a better understanding of the molecular pathways by which SCFAs affect the NAFLD phenotype and their potential as therapeutic intervention by employing the liver-on-chip system.
PhD project description: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease, affecting nearly one-third of the global population. To study NAFLD, current experimental models e.g., animals and 2D cell cultures, pose various limitations including species-specific differences and lack of complexity.
To overcome these limitations, I aim to engage the innovative, human-based organ-on-a-chip system. At this moment, there are no approved pharmacological interventions for NAFLD. Alternatively, lifestyle interventions are deemed unsustainable now, but these could become an attractive option if provided with a molecular basis for nutriceuticals. Interestingly, short-chain fatty acids (SCFAs), fermentation products of our intestinal microbiota from dietary fiber rs, could provide such basis as they attenuate fatty liver disease both in animal models as well as clinical studies.
Here, I aim to establish the underlying mechanisms of their effects to provide novel strategies in the prevention or treatment of NAFLD.To achieve this, I have defined three sub-objectives:
1. Understanding the biological effects of SCFAs on the liver using NAFLD on-a-chip. By co-culturing hepatocytes with Kupffer cells followed by lipotoxic stimulation with free fatty acids and TNFα, steatohepatitis is triggered. Relevant steatohepatitis-related physiological readouts will be assessed. Thereafter, I wish to characterize the fatty vs. inflammatory (NASH) phenotype of NAFLD by physiological readouts.
2. Establishing the molecular mechanisms underlying the effects of SCFAs on NAFLD. To explore the complete differential profile of SCFAs in NAFLD, we will employ various omics analyses including RNA-sequencing, proteomics and lipidomics.
3. Investigating downstream molecular pathways by using CRISPR/Cas9 gene-editing approaches on candidate genes identified in objective 2 and utilizing tools at hand by mydepartments in with the UMCG iPSC/CRISPR facility.
To summarize, I expect to gain a better understanding of the molecular pathways by which SCFAs affect the NAFLD phenotype and their potential as therapeutic intervention by employing the liver-on-chip system.
| Laatst gewijzigd: | 01 maart 2024 14:09 |