Nicolai Van Oers, Ph.d.
Chief Operations Officer
UT Southwestern Medical Center
Project 1: Patients with primary immunodeficiency diseases (PID) are unable to respond to viral, bacterial, and fungal infections properly. Patients with one PID called 22q11.2 deletion syndrome can present with a small thymus, hypoparathyroidism, cardiac problems, and for 1/3 who progress to adulthood, schizophrenia. The thymus is required for the generation of the T cells that combat infections. To better understand their immune system problems, we performed a microRNA profiling study of the blood and thymus. MicroRNAs are small, non-coding RNA molecules that control gene expression. We discovered that the 22q11.2 deletion syndrome patients exhibit an intriguing microRNA dysregulation; hyper-variable miR expression values and abnormal group miR behavior. We are studying the developmental abnormalities that occur in these patients, with an emphasis on how microRNAs affect these pathways.
Project 2: Stress, elicited by malnutrition, infections, trauma, surgery, alcoholism, steroid injections and even pregnancy, causes acute and chronic immune system abnormalities. The thymus is particularly sensitive to stress, with cell dying, eventually leading to a weakened immune system. Hypoplastic, or small thymii, are very common in the elderly, which leads to their poor responses to vaccines. We identified several distinct microRNAs in the thymus that are either stress-responsive or poorly expressed in hypoplastic tissues. Our current research efforts are exploring the role of 4 such microRNA (miR-128, miR-181d, miR-185, miR-205). One of these, miR-205, exhibits a stress-responsive, thymic epithelial specific expression pattern. This suggests an important role for this microRNA in epithelial cell function and survival. We are using conditional knockout mice to test this possibility