Michael Vermeulen, PhD candidate Babak/Craig Lab The Vanishing Y: Exploring the role of mosaic loss of chromosome Y in neurodegeration and cancer As men age they experience a gradual loss of the Y chromosome (LOY) in their cells, specifically within immune cell-types. Recent, large-scale epidemiological surveys have found
approximately 70% of men older than 70 years of age have a detectable loss of their Y chromosome. Furthermore, a range of association studies have linked LOY to several age-related diseases including heart disease, Alzheimer’s, cancer, and macular degeneration. Also, we know that LOY is one of the most common chromosomal aberrations observed in male cancers (occurring in about ~28% of primary tumors). Despite the frequency of LOY and its association with disease, relatively little is known about its mechanisms and its role in disease pathology. Although recent mouse studies suggest LOY can directly cause disease, we still don’t know if it directly causes disease or is a passenger biomarker of degrading genomic instability. My Master’s research aimed to better understand LOY in brain tissue, with a specific interest in the cell-types LOY tends to accumulate in. We found that LOY is particularly common in the microglia, the main immune cell in the brain and a cell-type with important roles in neurodegerative processes. My PHD research investigates the role of LOY in cancer, and its potential use as a therapeutic target. We plan to use CRISPR-cas9 editing systems to engineer isogenic cell lines differing only by the presence of the Y chromosome. We will then test for LOY-specific genetic vulnerabilities using CRISPR loss-of-function screens with the goal of highlighting potential weaknesses in LOY cells that could be exploited as a cancer therapy. Comments are closed.
|
Categories
All
Archives
April 2024
|