Keio University Human Biology-Microbiome-Quantum Research Center (WPI-Bio2Q) held a seminar as follows.

11:00 -12:00, April 27, 2026

Venue:
2F Meeting Room, Center for Integrated Medical Research, Shinanomachi Campus, Keio University

Speaker:
Soumya Raychaudhuri, MD, PhD
Professor of Biomedical Informatics
Harvard Medical School
USA

Title:
“Wrestling a disease locus to the ground: Defining the mechanism of CD40 in human autoimmunity”

Translating statistical associations from GWAS into biological mechanisms remains a formidable challenge. For example, we and others have established the CD40 locus as a major risk factor for autoimmune conditions like rheumatoid arthritis and multiple sclerosis.
In this talk, I described multidisciplinary strategies to define disease mechanisms, specifically using dynamic eQTL mapping in single cells. By modeling genetic effects across continuous cell-state trajectories, we capture regulatory signals that emerge only during specific stages of immune activation. We apply this to autoimmune loci, and immune cell states – including the CD40 locus.
We apply our novel CRAFT-seq platform, which enables us to link the effects of base-pair resolution CRISPR edits to simultaneous single-cell transcriptomic and surface-protein outputs. Our data reveal a protective SNP that disrupts a Kozak sequence, selectively reducing CD40 protein levels without altering mRNA expression. This reduction raises the threshold for B cell activation and triggers significant trans-regulatory effects that are most prominent in activated naive B cells. In this specific context, the SNP suppresses gene modules essential for downstream signaling. These findings demonstrate how subtle non-coding variation scales into systemic disease. They provide a blueprint for how non-coding variants can be used to define disease mechanisms.