John F. Engelhardt

IBA-MARC Core Mentor
DEO and Chair, Department of Anatomy and Cell Biology
Professor, Department of Anatomy and Cell Biology; Assistant Research Scientist, Department of Internal Medicine
Department of Anatomy & Cell Biology
Carver College of Medicine
University of Iowa
STEM Area of Research: 
BS, Biochemistry, Iowa State University
PhD, Human Genetics, Johns Hopkins University
1-100 BSB

Research in the Engelhardt laboratory focuses on the molecular basis of inherited and environmentally induced diseases, and using gene therapy to treat these disorders. Included are two major research areas: 1) the study of lung molecular and cellular biology as it relates to the pathogenesis and treatment of cystic fibrosis (CF) lung disease and associated diabetes, and 2) the molecular mechanism underlying redox-mediated injury and the development of molecular therapies for ischemia/reperfusion injury, sepsis, and the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Research on lung biology includes the study of adult epithelial stem cells and their niches in the airway, and dissecting the pathogenesis of lung disease in animal models of cystic fibrosis. The laboratory is currently elucidating transcriptional signals important for early establishment of the airway glandular stem cell niche, and for mobilization of stem cells from this niche following airway injury. The newly generated ferret and pig models of cystic fibrosis are being used to understand how stem cells in the adult airway respond to injury resulting from dysfunction of CFTR (the chloride channel that is defective in cystic fibrosis). These new genetic models of CF are also being used to dissect pathophysiologic mechanisms of disease and to develop gene therapies that target the lung with recombinant adeno-associated virus. A second area of interest is the dissection of pro-inflammatory, redox-dependent, signaling pathways in the liver and central nervous system. Such studies are aimed at the treatment of environmentally induced liver injuries—those resulting from sepsis, ischemia/reperfusion, and (in the case of ALS) motor neuron injury. We are using rodent transgenic and knockout models to better understand the mechanisms that are involved in inflammation and injury and are controlled by reactive oxygen species. Of particular interest in this area are mechanisms of redox-regulated NFκB activation via several NADPH oxidase complexes (Nox1, Nox2 and Nox4), whose roles include generating intracellular superoxides in response to extracellular pro-inflammatory cytokine signals (IL-1beta and TNFalpha pathways are a major focus). This redox-signaling program heavily utilizes recombinant viral vectors, transgenic/knockout mice, and proteomic approaches to address basic aspects of pathophysiology, and also to generate new therapies capable of promoting organ regeneration and repair while also minimizing the deleterious inflammatory responses to injury. Current NIH Funded Projects Mechanisms of AAV Transduction in the Airway (R01 Funded) Biology of Submucosal Gland Stem Cells in the Airway (MERIT AWARD R01 Funded) Redox Mechanisms of Ischemia Reperfusion Injury in the Liver (R01 Funded) Pathological Evaluation of a Cystic Fibrosis Ferret Model (ARRA – Funded) Airway Physiology and Pathophysiology in a Porcine CF Model (PPG Funded) Complete publication list: