Trained as an immunologist, I have focused on how genetic and environmental factors contribute to onset of autoimmune diseases with special focus on sex-bias. My laboratory is focused on investigating immunopathology of aging related chronic conditions like rheumatoid arthritis and associated diseases along several tracks. My laboratory has made seminal discoveries in these areas of research. To simulate human autoimmune diseases and sex bias, we have generated mice expressing autoimmune-associated HLA alleles. Using the transgenic mice we have generated mouse model that mimics human rheumatoid arthritis in sex-bias and autoantibody profile.
Besides genetic factors, environmental factors including smoking and microbiome have been suggested to contribute to pathogenesis and sex-bias. I have been at the forefront of developing microbial markers for pathogenicity as well as therapy. We have generated microbial biomarkers for rheumatoid arthritis and defined sex- specific microbes associated present in sex-specific which we are modeling in animals to understand the mechanism. Diet has a big role in determining microbial composition. I believe that the immune system can be balanced by improving diet and supplementing the beneficial bacteria lost in patients. We have isolated a novel gut bacterium from human biopsy and using a novel approach shown that it can modulate mucosal and systemic immunity and reduce systemic inflammation. The gut bacterium, Prevotella Histicola, was first tested in transgenic model of rheumatoid arthritis and is now in phase 2 trial for autoimmune diseases. My training in mucosal immunology and rheumatologic diseases enables me to utilize my experiences from patient data to humanized mouse models and vice versa.
Smokers generally develop autoimmune diseases with increased severity. We have generated a model which recapitulates the pathology of lungs of patients with rheumatoid arthritis. We are working to determine whether joint-gut-lung axis is a prominent axis defining disease development. I am closely working with many clinicians from rheumatology, Pulmonology, Gastroenterology and Microbiome divisions as well as many external investigators to determine mechanisms of pathogenesis and treatment for rheumatoid arthritis. Infections play a role in autoimmunity though not a single pathogen has been implicated. We have shown that clearance of infections, autoimmunity and longevity have a clear connection with genetic predisposition and microbiota.
I teach undergraduates, graduate students as well as Core curriculum for rheumatology fellows. I am also an active member of Cancer Center and Immunotherapeutic Program at Mayo Clinic.