Project Overview
Investigating the role of Kruppel-like factor 4 as a tumor suppressor in mouse embryonic fibroblast and colorectal cancer cells lines
Department(s)
Biology
Abstract
Kru¨ppel-like factor 4 (Klf4) is a zinc-finger-containing transcription factor with tumor suppressor activity that is mutated in various cancer types including colorectal cancer. Despite ample contextual evidence of Klf4’s role in cancer development, the specific molecular mechanisms targeted are not fully understood. Earlier research in our laboratory discovered that the lack of Klf4 in mouse embryonic fibroblasts (MEFs) resulted in an increase of reactive oxygen species (ROS) that was associated with increased DNA damage. We also demonstrated that loss of Klf4 impairs the cellular recycling process known as autophagy. In addition, our results indicate that cells lacking Klf4 are unable to recover from mitochondrial damage. Our data suggests a central role for Klf4 in mitochondrial integrity, which can mitigate DNA damage due to ROS, and may greatly impact cellular metabolism. However, the underlying mechanisms of how Klf4 expression and function is involved in all these processes and prevent genomic instability are unclear. Based on our previous findings and resulting hypotheses, two specific aims will be used to investigate the role of Klf4 in regulating DNA damage and Ferroptosis, a newly discovered iron dependent programmed cell death. In Aim 1, we will determine the mechanisms through which Klf4 regulates DNA damage by investigating the impact of altered expression and function of Klf4 on the expression and function of DNA repair genes and thier downstream molecules in normal and cancer cells. In Aim 2, we will identify the underlying mechanism by which Klf4 induced Ferroptosis to prevent abnormal cell division. We will also evaluate the relationship between Klf4 and Ferroptosis related genes. The long-term goal of this study will further advance our understanding of molecular mechanisms responsible for the formation of cancer. The summer students will participate in the design and execution of short-term or long-term projects that incorporate multiple levels of analysis and provide the opportunity to see projects from their inception to publication.
Student Qualifications
Knowledge of cell culture would be desirable
Must completed Biol182
Number of Student Researchers
2 students
Project Length
10 weeks