In the Hoffman laboratory, we study how microbes contribute to chronic diseases of children. The microbes we study are found in the lung and gastrointestinal (GI) tracts of children with these diseases.
Our research team gathered on the banks of the Montlake cut on a sunny March afternoon outside the UWMC.
Research Summary: I am a clinician-scientist; clinically, I am a pediatric pulmonologist, focused on the health and disease of children’s lungs. One of the most vexing problems I face in this clinical role is how to treat children with chronic infections, particularly those suffered by people with cystic fibrosis (CF), chronic endobronchial tubes, and non-CF bronchiectasis. Because of my frustration with these infections, my laboratory efforts concentrate on how to better study and treat these devastating infections. As nutritional failure plays a role in the outcomes of many of pediatric lung diseases, I am also interested in how the GI microbiota impact early growth and nutrition. My hope is to ameliorate or halt the lung diseases many chronic infections generate, and to improve the lung health of children worldwide.
Research Summary: Overall, my work focuses on genotypic and phenotypic characterization of microorganisms recovered from the CF lung environment. I am specifically interested in defining mechanisms of resistance, hypersusceptibility, and dependence to antimicrobial agents in clinical CF bacterial isolates. In parallel, a current project is focused on antibiotic susceptibility profiling of bacterial communities in CF sputum.
Research Summary: CF is a multi-organ system disease, however the hallmark clinical manifestations result in respiratory failure and gastrointestinal complications. In effort to better understand CF physiology and mechanisms of disease, my work focuses on characterizing the microbiota of both the lung and gastrointestinal tract in CF patients.
Research Summary: My research focuses on interspecies interactions between Pseudomonas aeruginosa and Staphylococcus aureus. Co-infection with these two bacterial species occurs commonly in people with cystic fibrosis and is associated with higher lung disease morbidity and mortality. I study how these microorganisms interact through secreted products, such as proteins and small molecules, and how these interactions influence both biofilm formation and the host immune response.
Research Summary: Staphylococcus aureus is the bacterium most commonly cultured from CF patients, and I am particularly interested in small colony variant (SCV) Staphylococcus aureus. SCVs are frequently isolated from antibiotic-refractory S. aureus infections. Moreover, the recovery of SCVs has been correlated with both worse clinical outcome and poor response to antibiotics. My thesis research will focus on these prevalent yet understudied S. aureus variants; I am interested in the in vivo mechanisms of emergence and characterizing physiological growth characteristics indicative of persistence, i.e. biofilm formation, intracellular survival, and metabolic profiles. My research could have broad implication for how S. aureus infections are managed in chronic infections like CF as well as relevance for osteomyelitis, soft tissue, and device related infections.
Additionally, SCVs grow poorly or not at all on standard antibiotic susceptibility testing (AST) media and quickly revert to wild-type in vitro, making AST under standard conditions problematic. Therefore, directing antibiotic treatment in patients with SCV infections is not universally practiced. Based off these issues, a component of my thesis research has been to design and optimize AST methods for S. aureus SCVs. This project has direct clinical application, and could potentially be implemented across clinical microbiology laboratories.