Celiac disease is an immune-mediated gastrointestinal disease that arises in patients with a permissive HLA-DQ2/HLA-DQ8 genetic background. There is currently no treatment for celiac disease apart from gluten avoidance, which is not always effective. Celiac disease shows a familial clustering and occurs more frequently in patients with Down Syndrome or those carrying germ-line mutations in STAT gene. The lab is testing the hypothesis that JAK-STAT might be an essential genetic determinant for celiac disease. The lab has been screening for new genetic alterations in the JAK-STAT pathway in the familial celiac disease cases through Whole Exome Sequencing. We investigate the impact of JAK-STAT overactivation on gluten-specific CD4+ T cells from genetically susceptible celiac disease patients. The long-term goal is to translate the research finding into the potential clinical use of JAK inhibitors in celiac disease.
The immune system plays a pivotal role in protecting hosts from various infections, deleterious inflammation, and malignancy. We are conducting patient-oriented investigations to determine the genetic susceptibilities of humans to common gastrointestinal infections. We are actively recruiting patients with severe infection due to Helicobacter pylori, CMV, EBV, rotavirus, norovirus, SARS-CoV-2, amebiasis, and strongyloidiasis. In addition, we are interested in deciphering the immunologic defects and conducting translational research for gastrointestinal involvements in patients with Common Variable Immune Deficiency and selective IgA deficiency. In collaboration with colleagues, our lab will work on the genetic diagnosis and mucosal immunologic defects in patients with Very Early Onset Inflammatory Bowel Disease (VEO-IBD) and disseminated granulomatous disease in IBD.
Our lab is currently developing both computational and biological tools to facilitate clinical translational research in Mendelian diseases affecting digestive organs, including eosinophilia and eosinophilic esophagitis, cryptogenic liver cirrhosis, unknown causes of abnormal transaminitis and primary sclerosing cholangitis. We are developing several tools to facilitate translational research, including a few web apps for direct patient enrollment and community engagement; a cloud computing system for deep phenotyping and genomic annotation, a bench platform for functional characterization of rare variants using human cell lines, organoids, and iPSCs. The goal of our research is to learn the common biological mechanisms underlying the illness from those rare individuals, so called "Experimental in Nature", ultimately to advance the diagnosis and treatment in general.