The immune system plays a central role in human health - fighting infections, eliminating cancer cells, and maintaining internal balance. But when immune responses go awry, they can also drive inflammation, autoimmunity, and chronic disease. Immunogenomics is the study of how our genes influence the behavior of immune cells in both health and disease. Researchers in the Department of Genetics and Genomic Sciences (GGS) at the Icahn School of Medicine at Mount Sinai are leading efforts to decode the genetic and molecular signals that guide immune function - with the goal of enabling new diagnostics, therapies, and personalized approaches to treatment.
Laboratory, computational, and clinical scientists in GGS work together to identify the genetic variants that drive immune cell responses - both protective and pathogenic.
The immune system defends against infection and cancer through two arms: innate and adaptive immunity. Innate immune cells detect and process invading pathogens or tumor cells, activating T and B lymphocytes, which then mature into a diverse pool of memory cells with specialized functions. While these memory cells typically support long-term protection, in some cases they can trigger autoimmune responses and cause damage to the body’s own tissues.
Understanding the genes, mutations, and regulatory mechanisms involved in immune function has led to the development of immunotherapies now used to treat autoimmune diseases, infections, and cancer.
GGS researchers study the dynamic interplay between tumor cells and the immune system to reveal how tumor-associated genetic drivers influence immune biology and response to immunotherapy. Patient outcomes often vary due to differences in immune genotypes, which can shape both disease progression and therapeutic efficacy. To support these studies, GGS investigators have developed the largest centrally integrated resource of gene expression regulatory elements across human blood immune cell types.
In Inflammatory Bowel Disease (IBD) research, GGS scientists explore how genetics, the immune system, and environmental factors interact. They identified mutations in NOD2 associated with Crohn’s disease and discovered genetic variants in IL-23 receptor signaling that are strongly linked to both Crohn’s disease and ulcerative colitis. These foundational discoveries contributed directly to the development of anti-IL-23 immunotherapies now widely used in the treatment of IBD.
GGS investigators are also uncovering critical neuro-immune interactions. Communication between the immune and nervous systems is essential for healthy brain development, defense against infections, and tumor immunity. GGS researchers have identified Alzheimer’s disease risk genotypes associated with altered function in microglia - brain-resident immune cells essential to neural health. Parallel studies in autism spectrum disorders have revealed key genetic drivers and regulatory networks that shape neuro-immune dynamics.