Marina Saffold

Marina Saffold, a junior studying Neuroscience at Pomona College, developed a human-induced pluripotent stem cell (hiPSC) model of aged astrocytes to study mechanisms for neurodegeneration

In a landscape of increasing life expectancy, age emerges as the most significant risk factor for the development of neurodegenerative diseases and cognitive decline. BSRP is nothing short of transformative. Yes, it changed me as a researcher: I gained the skills to overcome obstacles in science, plan and execute my experiments, and dive deep into the background of a project to build confidence in my research area. But it also shaped how I seek to interact with the people around me and instill change in the world. I walk away from the Broad with thoughtfulness, intentionality, and some of the most meaningful connections I have made in my life.Changes in astrocyte function and their interaction with neurons during aging is an understudied pathway for neurodegeneration, especially given the pivotal role astrocytes play in supporting neuron survival, differentiation, and communication. Additionally, astrocyte inflammation has been observed in patients with many neurodegenerative diseases. Human induced pluripotent stem cells (hiPSCs) are an attractive model to study how age-related stress alters astrocyte function. However, the process of developmental reprogramming removes hallmarks of aging in hiPSCs. Therefore, the aim of my project was to develop a model of cellular aging in hiPSC-derived astrocytes. Recently published literature has identified three proteins (Lap2β, H3K9me3, and HP1γ) that exhibit decreased expression in aged fibroblasts and a “senescence cocktail” of small molecules that have been observed to reduce the expression of these chromatin proteins in a way that models aged cells. We hypothesized that these small molecules would similarly decrease the expression of chromatin proteins in hiPSC-derived astrocytes. Preliminary western blot and immunofluorescence assays for protein expression reflected the presence of aged phenotypes, including decreased expression of Lap2β and H3K9me3, in hiPSC-astrocytes treated with the senescence cocktail. Further optimization of this hiPSC model of aged astrocytes presents opportunities to assess alterations in astrocyte function and analyze samples with varying human genetic backgrounds, revealing mechanisms for how aging leads to the development of neurodegenerative diseases and cognitive decline

Project: Modeling neurodegeneration in human astrocytes through induced aging

Mentor: Rachel A. Battaglia, Stanley Center for Psychiatric Research