R. William DePaolo

PIBBS MENTOR

Assistant Professor

Molecular Microbiology and Immunology
Keck School of Medicine

Research Topics

  • Host-pathogen interaction
  • mucosal biology, immunology
  • infectious disease

Research Overview

Our bodies are home to an enormous ecosystem containing 100 trillion bacteria, a number which is 10 times greater than our own human cells. While these bacteria perform essential functions for our health and physiology, they are a dynamic community that can respond to biological and environmental pressures. These pressures include an individual’s genetic background, nutritional status, infection or repeated antibiotic use. Over time, and in certain contexts, these factors contribute to alterations in the composition, location and/or function of the microbiota. These changes may inhibit the growth and maintenance of normally healthy probiotic bacteria species making the intestine permissive for the growth and expansion of opportunistic bacteria. These shifts in “good” and “bad” bacteria have been associated with the onset and progression of both intestinal and systemic diseases. Due to the inherent plasticity of the microbiota, the manipulation of its communities is an area of research with the potential for significant therapeutic applications, however it remains largely unexplored.

The over-arching theme of my research laboratory is to understand the complex relationship between our immune system and the microbiota in different disease and nutritional states. To accomplish these goals we approach basic science questions by pairing standard metagenomic analysis with functional assays designed by our laboratory that examine the immunological status of the tissues and the microbiota. Understanding how the microbiota is altered and how our immune system responds to these changes will allow us to identify and develop novel bio-therapeutics using the microbiota or its associated factors.

Here are a few projects that are currently underway in the laboratory:

*Translational genetic studies and development of assays to assess the immunological signature of the microbiota in patients with inflammatory bowel disease. Our lab is currently working with the Department of Pediatrics at the University of Chicago, Children’s Hospital LA, Keck Hospital and LA County Hospital on a number of studies. We have two ongoing translational genetic studies one examining the immunopathophysiology of IBD in underserved minority populations and the second to evaluate the genetics of specific innate immune receptors in pediatric IBD patients. We also have currently undertaken a project to develop different assays to measure the immune-stimulatory nature of human stool in an effort to identify immunological signatures that can be associated with different clinical parameters of disease or responsiveness to therapies.

*Microbiota-associated immunotherapy. Using models of colorectal cancer and gastrointestinal infection caused by a food and water-borne pathogens, we have identified two different strategies to manipulate the microbiota. These studies are a perfect example of the multidisciplinary approach our lab uses in order to address important scientific questions. Specifically, these projects combine animal models, bacterial genetics, bacterial metabolism, metagenomics, bioinformatics and immune tolerance. Importantly, these studies have laid the groundwork for new areas of research using the microbiota in systemic diseases such as leukemia and lymphoma.

*Basic immunological studies in the regulation of intestinal homeostasis by the innate immune system. Our lab is also interested in how the immune system regulates the day-to-day function of intestinal responses. Currently, we have projects that examine the regulation of intestinal innate lymphoid cells, intestinal stem cells, and diet/metabolism. These projects are using models of intestinal injury and repair, attaching/effacing bacterial infections and nutritional status (diet and diabetes models).