The human microbiome is believed to be important to normal physiology but we have limited knowledge of how commensal bacteria dictate, for example, immunity and metabolism (i.e. effector functions). The most common method for studying human microbiota has involved the sequencing of bacterial DNA in patient cohorts. Sequence-based studies are likely to provide a short-term solution to expand our understanding of the small number of known signaling systems, however, I believe that unbiased functional discovery methods are more useful to identify the still largely unknown host-microbial interactions that contribute to human health. The focus of my laboratory is the study of host-microbial interactions by 1) developing methods for the systematic identification of human microbial effector functions and 2) determining the role of bacterial effectors in the pathogenesis of human diseases. This research platform represents a shift from “sequence first” studies of the microbiome to “function first” studies that are more easily translated into etiologic and therapeutic studies of commensal bacteria and human disease. To enhance this research platform we have active protocols to collect a variety of samples from humans with diseases associated with the microbiome including diabetes, obesity, colon cancer, cirrhosis and inflammatory bowel disease.
The clinical research focus of the laboratory is on patients with rare diseases that manifest as IBD as well as patients with highly refractory Crohn’s disease. We have an ongoing prospective cohort study that characterizes the bowel manifestations in patients with Hermansky Pudlak Syndrome (HPS). Patients with HPS develop a granulomatous colitis and we aim to understand what is similar or different to Crohn’s colitis by describing the phenotype, genotype, immune profile and microbial ecology in patients with HPS. We also have an ongoing protocol to study the effect of autologous stem cell transplant in highly refractory Crohn’s disease. This protocol aims to build on previous therapeutic efforts by initiating vedolizumab in the post-transplant period. In this study we will first characterize the cohort of patients with refractory Crohns disease and then will track their response to therapy throughout the study. Patients genotype, immune phenotype and microbiome will be tracked including phenotyping both of the peripheral and intestinal immune cell populations.