Yosenelys Fabian
Yosenelys is a rising junior at Vanderbilt University majoring in neuroscience. She investigated the role of AKAP11, a shared genetic risk factor for schizophrenia and bipolar disorder, in regulating ferroptosis. Her project examined how AKAP11 deficiency impacted lipid peroxidation in brain tissue and cultured astrocytes.
A-kinase anchoring protein 11 (AKAP11) is a shared genetic risk factor for schizophrenia and bipolar disorder. When I joined the Ó³»´«Ã½ this summer, I had no idea how much I would grow both as a scientist and as an individual. Through this incredible opportunity, I discovered that science is not just about conducting experiments perfectly but also about the people, perspectives, and ambition that drive the work we do. This program pushed me to look inward and understand how my own experiences influence the way I approach science and to recognize the importance of stepping outside my comfort zone. Most importantly, I learned the value of having a community that challenges and supports you, and the importance of considering perspectives beyond your own field. I’m grateful to say I am leaving this program with a deeper understanding of what it means to be a scientist, greater confidence in my skills, and a clearer vision of the kind of environment I want to build in science. In cultured cells, AKAP11 binds directly to the regulatory subunits of protein kinase A (PKA), anchoring the PKA holoenzyme to specific subcellular locations. However, its cellular functions in the brain remain poorly understood. Our preliminary transcriptomic analysis revealed upregulation of genes involved in lipid metabolism and ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, in both Akap11+/−and Akap11−/− astrocytes.
To investigate a potential role for AKAP11 in ferroptosis, we examined levels of the lipid peroxidation marker 4-hydroxynonenal (4-HNE) in brain tissue and cultured astrocytes. Immunohistochemistry of cortex tissue from Akap11+/+, Akap11+/−, and Akap11−/− mice revealed elevated 4-HNE levels in Akap11 deficient brains. In contrast, western blot analyses of primary cultured astrocytes did not show a significant change in 4-HNE levels. These findings suggest a cell type specific role for AKAP11 in modulating ferroptosis in vivo. Ongoing work aims to determine which cell types are most vulnerable to ferroptosis upon AKAP11 loss. Collectively, this study provides new insight into the cellular functions of AKAP11 and offers a potential mechanistic link between ferroptosis and the pathophysiology of schizophrenia and bipolar disorder.
Project: Defining the Role of AKAP11 in Ferroptosis in Mouse Brain and Cultured Astrocytes
Mentors: Xiaoman Liu and John Adeleye, Sheng Lab, Stanley Center for Psychiatric Research
