Joel Berletch PhD

UW Laboratory Medicine & Pathology
Research Assistant Professor

Email: joelb07@uw.edu | Phone: 206.685.2801

Our research focuses on X chromosome gene regulation and the effects of abnormal X and Y chromosome dosage on the transcriptome and epigenome. In mammals, the process of X chromosome inactivation, whereby one X chromosome in females is transcriptionally silenced, serves to balance X/Y gene dosage between the sexes. However, a sizable number of X-linked genes escape this silencing and represent a naturally occurring dosage imbalance with generally more expression in females. Changes in dosage of these “escapees” is thought to contribute to the many phenotypes observed in individuals with sex chromosome aneuploidy. These phenotypes include, but are not limited to, decreased cognition, cardiovascular deficiencies, and impaired immune response. Therefore, to study the effects of aberrant sex chromosome gene dosage in the development of disease relevant cell types, such as neural precursor cells (NPCs) and cardiomyocytes (CMs) we use human induced pluripotent stem cells (hiPSCs) with different numbers of sex chromosomes for in vitro differentiation and global analyses of transcription, histone modifications, DNA methylation, and functional phenotypes. Additionally, we use these hiPSCs with different numbers of X chromosomes to study sex differences in sex-biased diseases such as Alzheimer’s Disease.