Research Spotlight: Uncovering How Bacteria Impact Children's Health
Fernando Ruiz, PhD, an associate professor of research in the Department of Pediatrics, researches the pathogenesis of enterobacteria. That includes shigella, E. coli, and the bacteria associated with inflammatory bowel disease. This information can fuel better diagnostics, development of vaccines, or therapeutic strategies to combat these infections in children.
He shares what first drew him to this research and some of the surprising information about these bacteria and how they contribute to long-term health.
I love my job as a scientist because that gives me the opportunity to discover new things that can contribute to human health, and because my work also provides me with intellectual freedom, continuous learning, and the satisfaction that I can contribute to human knowledge. My name is Fernando Ruiz. I'm an associate professor of research in the department of pediatrics. My lab is interested in understanding the pathogenesis of enterobacteria such as Shigella, pathogenic E. coli, and those pathobionts associated with the inflammatory bowel disease. We study host pathogen interactions, mechanism of immunization, bacterial secretion systems that these enterobacteria uses to cause disease. My work in bacterial pathogenesis is aimed to enhance human health by uncovering the mechanisms of intestinal inflammation, intestinal pathology, immune evasion that bacteria orchestrate to cause disease. We can use this information for vaccine development, for new diagnostics, or to implement therapeutic strategies that we can use to battle infections that primarily affect children.
What are you working on right now?
My laboratory is currently funded by NIH/NIAID to study the cellular and molecular mechanisms of host-pathogen interactions, focusing on Enteroaggregative E. coli (EAEC), Enterotoxigenic E. coli (ETEC), and Shigella, which are major contributors to diarrheal diseases globally, primarily affecting children.
We use a sophisticated two-dimensional primary cell culture model derived from human intestinal stem cells, known as enteroids/colonoids. This model effectively mimics the natural intestinal environment and allows us to investigate colonic health and disease, as well as host-pathogen interactions, in a controlled manner to identify disease mechanisms and pathogen vulnerabilities. In addition to studying traditional pathogens, our research addresses the contributions of pathobionts to inflammatory bowel disease (IBD).
We employ cutting-edge technologies, including CRISPR-Cas9 gene editing in human intestinal organoids, to explore the roles of mucin receptors in homeostasis and in the onset of intestinal inflammation. By examining both pathogenic organisms and pathobionts, we aim to deepen our understanding of the complex mechanisms underlying inflammation during bacterial infections and IBD. Our ultimate goal is to identify novel therapeutic strategies to mitigate the effects of these factors on intestinal health.
What are the most intriguing potential clinical applications of your work?
Our work's most promising clinical applications involve developing targeted therapies for intestinal inflammation and mucosal barrier dysfunction. By studying how enteropathogens interfere with or manipulate intestinal signaling, we can identify strategies to protect intestinal cells. Identifying the mechanisms by which virulence factors and bacterial proteases drive inflammation could lead to drugs or biologics that block these activities, potentially reducing intestinal permeability and colitis symptoms. We have pinpointed receptors linked to inflammatory bowel disease (IBD), along with bacterial proteases that exert anti-inflammatory effects by targeting cytokine receptors in the gut.
Incorporating these therapeutic molecules into new or existing probiotics could offer innovative treatments for conditions such as ulcerative colitis and Crohn's disease, underscoring the importance of maintaining or repairing the mucosal barrier and suppressing exaggerated immune responses. Overall, our work aims not only to deepen understanding of the molecular underpinnings of intestinal diseases but also to translate these findings into meaningful clinical applications that can significantly improve patient outcomes.
What recent discovery/paper/presentation has impacted the way you think?
Recent breakthroughs in human stem cell technology and 2D/3D organoid cultures have transformed both scientific research and philosophical thinking by demonstrating that human cells can self-organize into complex, three-dimensional mini-organs outside the body.
Scientifically, this has revolutionized medicine by replacing traditional animal models with highly accurate human tissues, enabling researchers to observe real-time human development and test treatments directly on human biology. This has the potential to accelerate personalized medicine, as doctors can now grow patient-specific organoids to safely test drug therapies in a lab and determine which treatment works best before administering it to the patient.
What made you choose UVA Health as the place to conduct your research?
UVA Health stands out as an excellent research environment for its strong institutional support, top-tier collaborative teams, and state-of-the-art facilities that translate laboratory breakthroughs into clinical practice. When I was invited to join the Department of Pediatrics and Dr. Nataro's team, I readily accepted the opportunity.
What do you wish more people knew about your area of research?
I wish more people recognized how enterobacteria and certain pathobionts substantially affect inflammatory diseases and the integrity of mucosal barriers. Many are unaware that even asymptomatic infections can cause serious health problems, such as growth delays and persistent inflammation. The gut's mucus layer isn't just a passive shield; it also serves as an important communication channel.
Pathobionts and enteropathogens can produce metabolites and proteases that interact with and influence key mucosal signaling receptors vital for maintaining intestinal health. Understanding how microbes manipulate these mucosal receptors may be crucial for developing new, effective treatments.
How did you become interested in your area of research?
My fascination with microbiology began in my early school science classes, when I first viewed specimens through a microscope. I was amazed to discover an entire, unseen universe surrounding us. My interest deepened as I learned about Louis Pasteur's demonstrations that microorganisms are the causative agents of disease, as well as Robert Koch's identification of the specific bacteria responsible for anthrax and tuberculosis.
To pursue this interest, I earned a BSc, a master's, and a doctoral degree in Biomedical Sciences from the Center for Research and Advanced Studies of the National Polytechnic Institute (IPN) in Mexico City. During this time, I met Dr. Myron Levine, the Director of the Center for Vaccine Development (CVD) at the University of Maryland. His work on developing vaccines against malaria particularly fascinated me and motivated me to join the CVD. There, I worked on developing vaccines using engineered live-attenuated bacterial vectors, such as E. coli and salmonella, to deliver heterologous antigens.
Later, I met Dr. Nataro at the same center. He is a highly recognized pediatrician and researcher in bacterial pathogenesis and became my mentor for my postdoctoral studies at the University of Maryland at Baltimore. Over the years, I specialized in bacterial pathogenesis and its applications in vaccines and biotechnology.
In 2015, I became a faculty member at the University of Virginia (UVA), where I established myself as an independent investigator at the Child Health Research Center, a position I have held ever since.
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