Khairunnadiya (Nadia) Prayitno’s bio
Nadia Prayitno holds a doctoral degree for her work on the role of roX RNA in Dosage Compensation during Drosophila melanogaster embryogenesis, where she utilized a variety of molecular and cellular biology, biochemistry, NGS, and bioinformatic techniques. Since July 2021, she has been working with Dr. Mamatha Bhat at the University Health Network to elucidate transcriptomic and epigenetic changes that occur in post-transplant NASH. Concurrently, she is developing a model to study the effects of immunosuppression on the aggressive form of the disease progression.
Changes in Liver Transplant Recipients with Non-Alcoholic Steatohepatitis Indicate Dysregulation of Wound Healing
Diogo Pellegrina, Amirhossein Azhie, Elisa Pasini, Cristina Baciu, Sandra Fischer, Jüri Reimand, Mamatha Bhat
Background: Non-alcoholic fatty liver disease (NAFLD) is on the rise alongside increase in obesity and diabetes. It is estimated that one in three North Americans have NAFLD. Advanced NASH, the inflammatory form of NAFLD, can cause liver damage leading to a necessity for liver transplantation (LT). NASH can recur or develop de novo at an accelerated rate presenting stage three fibrosis by five years after LT. We aimed to examine the mechanistic basis of post-LT NASH.
Methods: The transcriptomes of post-LT liver biopsies presenting NASH, simple steatosis, or normal histology were profiled by RNA sequencing, and differential expression analysis performed to identify significant changes between groups and available non-LT NASH transcriptomes. Using ActivePathways, we identified enriched functional pathways and physical interactions of differentially expressed genes (DEGs).
Results: We found 118 DEGs out of 19,847 measured genes in post-LT NASH. We identified published markers of NASH and liver fibrosis including MUC1, AIML2, THBS2, IGF1, PCK1, and SOCS2. Our functional enrichment analysis showed significant transcriptomic changes in the PI3K-Akt pathway associated with metabolic alterations in NASH. Significant changes in gene expression were also linked to wound healing, cell cycle, and fibrosis. Our comparison to non-LT NASH confirmed the increased activation of wound healing and angiogenesis pathways in post-LT condition.
Conclusions: Our findings suggest the involvement of wound healing and fibrosis as a molecular basis for the accelerated development of fibrosis in post-LT NASH. Therefore, targeting mechanisms involved in liver fibrosis may be a therapeutic avenue for post-LT NASH to optimize graft survival.