Host-Microbial Interactions, Inflammation, and Immunity

Research in the Akhtar Laboratory is focused on understanding how viruses infect and cause pathogenesis in the pediatric brain. The approach that the researchers take is to identify clinical viral isolates associated with pediatric infection and poor neurologic outcomes, and bring these isolates back to the lab to assess the mechanism by which this occurs. They use viral whole genome sequencing, human and murine neuronal in vitro models, and murine in vivo models, as well as reverse genetics to understand clinical viral virulence factors. The current focus of the lab is to determine virulence factors contributing to neonatal herpes simplex virus encephalitis. 

The Coates Laboratory explores differences in the inflammatory response to viral respiratory infections in children and adults. Although young children and elderly adults bear a disproportionate burden of morbidity and mortality associated with viral respiratory infections, little is known about the mechanisms placing these populations at increased risk. The Coates Laboratory is currently investigating the role of innate immune responses in severity of illness in influenza and respiratory syncytial virus infections. Elucidation of the mechanisms underlying age-related susceptibility and resistance to disease may contribute to the broader understanding of innate immunity and its role in critical illness. 

The De Plaen Laboratory investigates the pathogenesis of necrotizing enterocolitis (NEC), a devastating disease of the intestine affecting premature infants, leading to chronic problems and sometimes death. Infants with NEC require much longer hospitalization and have a higher rate of neurodevelopmental delay, significantly impacting their quality of life. Even today, the causes of NEC are not well-understood and specific treatments are lacking. Animal models offer a unique avenue for deciphering disease pathogenesis. In our lab, we model NEC in neonatal mice and study the molecular mechanisms which lead to this disease in the neonatal intestine. 

The Kociolek laboratory houses a translational research program focused on various aspects of pediatric healthcare epidemiology and infection prevention and control, particularly Clostridium difficile colonization and infection in children. This research program is integrated with the Host-Microbial Interactions, Inflammation, and Immunity (HMI3) Program at Stanley Manne Children’s Research Institute, housed within Ann & Robert H. Lurie Children’s Hospital of Chicago. Our laboratory is primarily focused on various aspects of C. difficile colonization and infection, including clinical and molecular epidemiology, genomics, clinical microbiology and diagnosis, antibiotic resistance, and host immune response. Our overarching goal is to rigorously investigate this important pathogen in children to improve our ability to diagnose, prevent, and treat this infection.

A major pediatric research priority and the long-term goal of our laboratory is the identification of the etiology and pathogenesis of Kawasaki Disease (KD), the leading cause of acquired heart disease in children in developed nations. KD can result in coronary artery aneurysm (CAA) formation with resultant myocardial infarction and/or sudden death. Clinical and epidemiologic data are consistent with an infectious cause of KD, but the etiologic agent has proven difficult to identify. Our data support the likelihood that a "new" virus that enters through the respiratory tract and infects bronchial epithelium, traveling in macrophages to targeted tissues including coronary arteries, is the cause.

The Seed Research Group broadly studies the interactions of mammals and microbes to understand how microbial communities alter health and disease and how pathogenic microbes emerge from those communities to cause specific infections of the respiratory tract, urinary tract, blood, and central nervous system. The Seed Research Group combines human clinical studies, conventional and germ-free animal models, molecular genetics, immunology, biochemistry, structural biology, high-dimensional data computational analysis, and complementary 'omics technologies including genomics, metagenomics, transcriptomics, metatranscriptomics, and metabolomics to understand complex systems. We use the lessons learned from these molecular studies to design new diagnostics and therapeutics.