Over the last decade, new research has revealed that DNA is not the only means by which genetic information is encoded and transmitted in mammalian cells. A complementary system of “epigenetic” modifications have also been discovered which influences the activity of genes, but does not change the underlying DNA code of the genes themselves. Epigenetic regulation directs cell identity and function, helping guide embryonic cells down a specific path to become a specialized cell, such as a heart cell or immune cell. Epigenetic regulation is an essential, core mechanism of gene control and is active in all human cell types.
Recent studies have now linked abnormalities in epigenetic regulation to certain human birth defect syndromes. One of these syndromes, Kabuki Syndrome (KS), is linked to mutations in two important epigenetic regulator genes (KMT2D and KDM6A). Patients with KS have a variety of medical problems involving craniofacial structure, post-natal growth, intellectual development and immune deficiency. Pediatric Immunologist Dr. Andrew Lindsley and epigenetic scientist Dr. Artem Barski are proposing a variety of studies to explore how epigenetic defects can disrupt normal immune function, especially the generation of protective antibodies in the blood and mucosal tissue. Utilizing a genetically-engineered mouse which replicates human KS, Drs. Lindsley and Barski will explore the specific immune pathways affected by abnormalities in epigenetic regulation. They will test the effectiveness of several new classes of drugs in correcting the immune deficiencies seen in KS. Their findings may lead to new treatments for patients with KS as well as other patients with similar immune dysfunction.