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.
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
Mycobacterium tuberculosis infects 1/3 of the World’s population. Yet, the majority of infected individuals are unaware of their infection status. Vaccines have proven ineffective to date.
Using novel gene expression comparison and RNA sequencing approaches, we are uncovering previously unrecognized pathogenic mechanisms deployed by M. tuberculosis (see photos section).
Using this information, our goal is to engineer efficacious vaccines that will benefit mankind. The study is done in collaboration with Dr. Tawanda Gumbo.
Towards this goal, we have recently engineered novel mycobacterial expression vectors, the use of which are high-lighted on the cover of the journal, AEM (AEM cover). Some intriguing new discoveries are forthcoming!