Grant: Discovery Grants Program - Individual

In response to stress, cells adapt by altering their gene expression programs, and respond in a variety of ways ranging from the activation of survival pathways to the initiation of cell death, depending on the severity and duration of stress encountered. The mechanism of adaptation to stressful events remains unclear. Cardiomyocytes are cardiac muscle cells comprising cardiac muscle and a key player in forming heart function. We have demonstrated that hypoxia (low oxygen) and oxidative stress that are common stress induce cell death and organ dysfunction through activation of different signals. Recent studies have shown that small single-strand nucleotide ribosome acid (RNA) called as microRNA (miRNA) produced by a cell itself are changed upon exposure to stress. Our preliminary study also demonstrates that hypoxia stress significantly changes miR-711(one of miRNAs) expression in cardiomyocytes. By inhibiting various target molecules, miRNAs play crucial roles in various cellular processes and disease development. Due to their capacity to inhibite multiple target genes and their reversible regulation, miRNAs have emerged as a key controller of rapid cell responses to environmental changes and stress. However, how miR-711 is regulated and how miR-711 modulates cell death under stress is unclear. In this proposed study, we aim to investigate how microRNAs are regulated and their roles and function in response to low oxygen and oxidative stress through a series of cell culture experiments. The success of the study will provide new insight into understanding the mechanisms by which microRNAs function in stress responses. It will help understand how miRNAs are regulated and generated. It will also offer an excellent training environment for trainees.