3D and single-cell epigenome technologies for autoimmune disease
Ansuman Satpathy, MD, PhD
Assistant Professor
Stanford University
Pathology
General Audience Summary
Dr. Satpathy will use the cutting-edge technology that can obtain genomic information on the status of each gene in an individual cell, allowing the detection of molecular differences that could be obscured in a pool of cells. Applying this approach on immune cells from healthy individuals and people with autoimmune diseases—including type 1 diabetes, systemic lupus erythematous, and multiple sclerosis—he aims to identify the genes and pathways associated uniquely with each disease and shared between the diseases. He anticipates that these studies will lead to a single-cell atlas of autoimmune disease-associated genetic factors, leading to novel insights into the shared and disease-specific mechanisms governing each disease and propose new strategies for therapeutic intervention.Scientific Abstract
Genetic studies in patients with autoimmune disease have identified regions of the human genome that are associated with developing disease. However, the vast majority (90%) of these regions do not fall into typical protein-coding genes, but rather into non-protein-coding stretches of the genome that are sometimes referred to as the ‘dark matter’ of the genome. The primary function of these non-protein-coding sites is to impact the expression of disease-associated genes; however, technologies to identify these sites and their connection to protein-coding genes in primary cells have been lacking. We recently developed several genome sequencing technologies that enable the measurement and interpretation of non-protein-coding DNA regions directly in patient samples, which allows us to walk this ‘last-mile’ in mapping the effects of genetic mutations on disease development in patients. In this proposal, we seek to understand this new layer of genetic information and link autoimmune disease-associated DNA elements with the cellular and molecular targets that they impact to bring about disease in patients with autoimmune disease broadly, and specifically in patients with Type 1 diabetes, systemic lupus erythematous, and multiple sclerosis. We envision that these findings will lead to new insights into the pathogenesis of autoimmunity and nominate molecular and cellular pathways that could be targeted for disease therapy.