Poster #042, City of Hope
Dnmt3a Protects The Genomic Stability of Pancreatic Progenitors During Embryonic Development
Mentors: Victor Ruiz, BS, PI: Sangeeta Dhawan, PhD
The pancreas maintains glucose homeostasis and supports digestion. All pancreatic cells arise from rapid proliferation of progenitor cells, including insulin-producing beta cells. As replication can induce DNA damage, progenitors must defend their genome. The enzyme Dnmt3a establishes DNA methylation patterns during development that guide progenitors’ differentiation and preserve genomic integrity. Previous research in the Dhawan lab showed that Dnmt3a loss in pancreatic progenitors causes beta-cell dysfunction after birth. It remains unknown whether this occurs due to progenitor DNA damage during growth. Using antibodies to detect DNA damage (γH2AX), DNA replication (Ki67), and pancreatic progenitors (Pdx1), I will immuno-stain pancreas from control and Dnmt3a Knockout (KO) mice at Embryonic Day 13.5. Fluorescence microscopy will quantify DNA damage, replication, and damage within replicating progenitors to determine whether Dnmt3a loss increases DNA damage during progenitor growth. My findings will offer insight into healthy pancreas development and the developmental basis of pancreatic diseases.