Dr. Joshua Johnson's research project focuses on the Integrated Stress Response (ISR) pathway, a pivotal molecular system that might help with the regulation of ovarian aging.
Ovarian aging is a phenomenon that has a significant impact on women's reproductive health and overall well-being. While the decline in ovarian function occurs with aging, there is an increasing subset of younger women experiencing Primary Ovarian Insufficiency (POI). POI not only has implications on fertility but also has been associated with various health-related complications that can be detrimental to a woman's health. As medical science progresses, the focus has shifted towards finding better biomarkers to understand and predict the onset and progression of POI. Improved biomarkers offer a more comprehensive view of ovarian health and the potential risks associated. These advancements have identified the Integrated Stress Response (ISR) pathway as a cornerstone in regulating ovarian aging.
Dr. Joshua Johnson's research project focuses on the Integrated Stress Response (ISR) pathway, a pivotal molecular system that reacts to stressors within cellular structures. Central to this pathway is the eukaryotic initiation factor 2 subunit alpha (eIF2α). When activated, eIF2α governs protein synthesis, translating genes crucial for cellular survival under distressing conditions. The aims of Dr. Joshua Johnson's project are to: - Understand the role of the ISR pathway in ovarian aging. - Validate phosphorylated eIF2α as a biomarker for ovarian health. - Develop interventions to prolong ovarian function and mitigate risks associated with POI. - Compare P-eIF2α levels in normal vs. accelerated ovarian aging models. - Bridge the gap between research findings and clinical applications. - Explore ways to enhance cell survival in the ovaries. In essence, the project aims to understand and address the challenges of ovarian aging through the lens of the ISR pathway.
- Test the hypothesis that blocking dephosphorylation of P-eIF2α (preventing ISR checkpoint recovery) in wild- type mice will slow follicle loss and extend fertility and fecundity, without deleterious effects on offspring health. - Test whether follicle loss in mice is enhanced by the converse control experiment, enhancing the dephosphorylation of P-eIF2α using the compound ISRIB.
- Test the hypothesis that blocking dephosphorylation of P-eIF2α (preventing ISR checkpoint recovery) in human ovarian cortex will slow follicle loss both by enhancing primordial follicle arrest and by blocking the death of growing immature follicles. - Test whether follicle loss is enhanced by the converse experiment, enhancing the dephosphorylation of P- eIF2α using the compound ISRIB.