Research is the means through which medicine advances. Members of the Department of Immunology conduct leading-edge research into functions and disorders of the body’s immune system, with the ultimate goal of enhancing treatments and minimizing or eradicating diseases.
Among the research projects currently under way in our laboratories:
Epithelial cells that line the intestinal surface are in constant contact with the vast microbial communities that inhabit the intestine. Although intestinal microbes perform beneficial functions, they can still cause disease if they cross intestinal epithelial barriers and invade deeper host tissue. Despite the enormous numbers of gut bacteria, microbial incursions across the intestinal epithelial surface are relatively rare. This is because the intestinal epithelium plays a key role in sequestering bacteria in the gut lumen and preventing their penetration of host barriers.
A major goal of my laboratory is to understand how gut epithelial cells "keep the peace" with resident microbes. To deepen our understanding of these interactions, we use a multidisciplinary approach that includes biochemical analyses of new antibacterial proteins, in vivo analyses of the pathways by which gut epithelia sense bacteria, and creation of animal models to determine how epithelia regulate microbial interactions with host tissues. We hope that our studies will lead to fundamental insights into bacterial-epithelial interactions and will affect our basic understanding of how mammals maintain symbiotic relationships with their indigenous microbial communities.
Nicolai van Oers
Lab members are studying the regulation of immune responses during normal and pathological conditions with an emphasis on:
- MicroRNA regulation of immune responses.
- Molecular basis of human primary immunodeficiency diseases with small RNA and microRNA profiling.
- Pathogenic mechanisms of Mycobacterium tuberculosis.
- Contribution of novel signaling domains to T cell functions.
- The regulation of IL-6 in sepsis and tumorigenesis.
Our laboratory is focused on delineating the molecular mechanisms underlying the autoimmune diseases, particularly systemic lupus erythematosus (SLE). SLE is a chronic multifaceted autoimmune disease characterized by multiple autoantibodies that can affect almost every organ of the human body.
The ongoing projects in our laboratory include:
Identification and Characterization of Lupus Susceptibility Genes
Lupus is polygenic and multi-factorial in origin. Thanks to recent advances in high throughput genomic analysis technology, a number of novel genes and genomic loci that are highly related with lupus are being uncovered and characterized.
We are using DNA microarray, SNP genotyping, and second-generation deep sequencing for analyzing lupus genes in animal models and patients and have identified several lupus susceptibility genes. These studies will lead us to better understanding of the molecular mechanisms of lupus disease.
Identification of Novel Biomarkers of Lupus
Lupus is a complex disease and potentially life threatening. Currently there are no specific biomarkers for disease prediction, early diagnosis, or prognosis for treatment.
Over the past years, we have utilized an array-based proteomic technology for screening serum biomarkers from lupus and incomplete lupus patients. Dozens of novel biomarkers that are related with different phenotypes have been uncovered.
Ongoing efforts are focused on the validation of biomarkers using alternative methods and developing assays that can be used for clinical diagnosis.
Targeted Therapies for Treatment of Immune-Mediated and Lupus Nephritis
Lupus nephritis (LN) is the most severe complication of lupus, and currently available therapies for LN are far from being optimal and often have serious side-effects.
We have identified tissue kallikrein as a potential therapeutic target for LN. Now we are establishing a targeted molecular delivering system using genetic modified Mesenchymal stem cells as a vehicle to deliver the Klk1 to disease tissue in animal models. The success of this strategy will lead us to design new therapeutic strategies for the treatment of human lupus nephritis.