Laboratory, computational and clinical scientists at the Department of Genetics and Genomic Sciences (GGS) are working together to determine the genetic variants that trigger immune cell responses that cause disease, as well as healthy immune responses.

Our immune system relies on first line (innate) and second line (adaptive) immune responses that protect us from infections and prevent tumor growth. Innate immune cells process invading pathogens and tumor cells to activate T and B lymphocytes, which mature into a diverse population of memory cells with complementary functions. Memory cells help to eliminate infected and tumor cells, but in rare occasions may cause significant damage to our own tissues, including autoimmunity.

Uncovering the genes, associated mutations, and regulatory mechanisms underlying protective and disease-associated immune responses has led to the development and approval of immunotherapies treating autoimmune diseases, infections, and cancer.

GGS researchers investigate the complex bi-directional cross-talk between tumor cells and the immune system to identity how tumor-associated genetic drivers shape tumor immunobiology and responses to immunotherapy. Patient responses are often confounded by the diversity of human immune genotypes, which can drive specific pathologies. GGS researchers have developed the largest centrally integrated resource of gene expression regulatory elements across human blood immune cell types.

To understand the pathophysiology of Inflammatory Bowel Disease (IBD), our researchers investigate the complex interactions between our genes, immune system and the environment. GGS scientsits have identified that mutations in the gene NOD2 are associated with Crohn’s disease, and discovered that genetic variations in the genes involved in IL-23 receptor signaling are strongly associated with Crohn's disease and ulcerative colitis. This pioneering research led to the development of anti-IL23 immunotherapies, which are now widely used to treat IBD.

Close communication between our immune and nervous systems directs healthy brain development, response to infections and tumor immunity. Across GGS, researchers discover the genomic regulation of neuro-immune interactions in neurodevelopmental and neurodegenerative disorders. Significant discoveries include the identification of Alzheimer’s disease risk genotypes that are associated with functional changes in microglial cells. These macrophage-like brain immune cells are key to healthy brain development and function. In parallel efforts, GGS scientists discover the genetic drivers and genomic regulation of neuro-immune interactions in autism spectrum disorders.