- How maternal immune factors regulate neonatal microbiota. Gut colonization of commensal bacteria decreases the risk of neonatal sepsis. This suggests that dysbiosis of the neonatal gut microbiota may represent a risk factor and contribute to increased incidence of infection in infants. Our ongoing experiments show that host adaptive immune status plays a key role in shaping the gut microbiota. They beg the question, however, of the relative contributions of maternal and de novo immunity sources to the observed microbiota changes. In an NIH-funded project, we propose to focus on the effects of maternal factors, in particular those transferred through the milk and placenta, on the development of neonatal microbiota.
- Role of gut microbiota in systemic lupus erythematosus (SLE). SLE is a very complex autoimmune disorder with no known cure. It is characterized by severe and persistent inflammation that damages multiple organs, including skin, kidney, lung, joint, heart, and brain. More than half of patients suffer from lupus nephritis, a leading cause of death in patients with SLE. Current treatments for lupus nephritis are primarily nonselective immunosuppressants. They can effectively reduce the risk for renal failure, but the side effects are a major cause of concern. There is an imperative need for new treatment strategies against lupus nephritis, for which a better understanding of disease pathogenesis is required. Perturbation of gut microbiota has been shown to be associated with many autoimmune diseases, but little is known about the role of gut microbiota in SLE. We study SLE-associated gut microbiota in both mouse and human as a pathogenic mechanism driving the disease.
- Renal-infiltrating dendritic cells in the pathogenesis of lupus nephritis. Lupus nephritis manifests as inflammatory infiltrates in the glomeruli and tubulointerstitium of the kidney. A recent study has revealed that the severity of tubulointerstitial lesions, versus the glomerular counterpart, is a stronger predictor of prognosis in lupus nephritis. We have found that dendritic cells accumulate, specifically, in the tubulointerstitial region of nephritic kidneys for both human lupus patients and lupus-prone mice. However, their function in lupus nephritis is unknown. We thus aim to delineate the pathogenic role of renal-infiltrating dendritic cells in the pathogenesis of lupus nephritis.
- Generation of humanized lupus mouse model. Numerous mouse models have been employed to understand the pathogenesis of lupus and to test potential therapies. Although each model has unique advantages, effective treatments in mouse models often do not translate to human disease. We therefore aim to generate human-mouse chimeras for lupus research.
- Dr. Ansar Ahmed, Department of Biomedical Sciences and Pathobiology
- Dr. Chris Reilly, Department of Biomedical Sciences and Pathobiology
- Dr. Tom Cecere, Department of Biomedical Sciences and Pathobiology
- Dr. Bernard Jortner, Department of Biomedical Sciences and Pathobiology
- Dr. Michelle Theus, Department of Biomedical Sciences and Pathobiology