Paula I. Watnick, MD, PhD

Boston Children's Hospital

Academic Titles

Professor, Pediatrics, Harvard Medical School

Research Program Affiliation

Member, Cancer Genetics and Epigenetics

Research Abstract

Over the past twenty years, my laboratory has used bacterial genetics, genomics, proteomics, lipidomics, and metabolomics approaches to probe the interaction of microbes with the host intestine. We use both the common fruit fly Drosophila melanogaster, mammals, and enteroids as models. Our lab is one of few pursuing this line of investigation in Drosophila that has extensive expertise in bacterial and eukaryotic genetics, pathogenesis, and physiology. As a result, our lab has made and will continue to make unique contributions to the field. For instance, our laboratory developed the Drosophila model of oral Vibrio cholerae infection, which is now used by researchers worldwide. Using this model, we discovered that the short chain fatty acids and tryptophan provided by intestinal bacteria are critical for host metabolic homeostasis and survival of intestinal infection. This work inspired experiments with germ-free flies that led to the remarkable conclusion that the commensal microbiota of this model host regulates intestinal innate immune signaling and metabolism via chromatin remodeling specifically in enteroendocrine cells. This work, which establishes the existence of the long-hypothesized immunoendocrine axis and provides an underlying mechanism, is described in publications in Cell Metabolism and Immunity. This important line of investigation, which may ultimately inform new prebiotic and probiotic therapies to prevent intestinal infection and malignancy, and to treat chronic metabolic diseases.