My research interests
1) Q223R Leptin receptor polymorphism and innate immunity: The Q223R leptin receptor polymorphism in humans and mice is associated with increased susceptibility and severity of illness from bacterial infections in preclinical models and humans. The Q223R leptin receptor polymorphism also influences susceptibility to Klebsiella pneumonia by altering immune and inflammatory responses in the lung. This project integrates a preclinical model with a human cohort in the Michigan Genomics Initiative to examine the impact of the polymorphism on innate immunity to define how variation in leptin signaling affects bacterial defense and Klebsiella pneumonia risk and severity.
2) Lipodystrophy, leptin deficiency, and susceptibility to respiratory tract infections: Respiratory tract infections are a leading cause of death in patients with lipodystrophy syndromes, rare disorders characterized by loss of adipose tissue and type 2 diabetes. Patients with lipodystrophy are leptin-deficient and are treated with metrileptin, a drug that replaces leptin and improves metabolic and immune function. However, many patients discontinue treatment due to the development of anti-leptin antibodies. As an alternative, treatment with tirzepatide, a dual-acting glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) agonist. While this treatment improves blood glucose homeostasis, its impact on immune function is unknown. We will determine how lipodystrophy impairs host defense in mice and if treatments used for diabetes and leptin replacement in lipodystrophy are protective against bacterial pneumonia.