Dr. Piantadosi's laboratory has special expertise in the pathogenic mechanisms of acute organ failure, particularly acute lung injury (ALI), with an emphasis on the molecular regulatory roles of the physiological gases— oxygen, carbon monoxide, and nitric oxide— as they relate to the damage responses to acute inflammation. The basic science focuses on oxidative processes and redox-regulation, especially the molecular mechanisms by which reactive oxygen and nitrogen species transmit biological signals involved in the maintenance of energy metabolism and mitochondrial health, but also contribute to pathogenesis and to the resolution of tissue injury.
Clinically, ALI and the related syndrome of multiple organ failure has a high mortality, which is related to the host inflammatory response, but is not well understood scientifically; thus, the laboratory is devoted to understanding these mechanisms in the context of the host response to relevant but well-controlled experimental manipulations including hyperoxia, bacterial infections, toxic drugs, and cytokine/chemokine signals. The approach relies on animal models, mainly transgenic and knockout mice, and cell models, especially lung and heart cells to evaluate and understand the physiology, pathology, and cell and molecular biology of the injury responses, to test independent and integrated mechanisms, and to devise interventions to prevent damage.
Apart from the lung, significant work is devoted to understanding damage to the heart, brain, liver, and kidney caused by these immune mechanisms, specifically emphasizing the role of mitochondria, key targets and sources of oxidative damage. This damage compromises their ability to support energy homeostasis and advanced cellular functions, and impacts on the important roles these organelles play in cell death by apoptosis and necrosis as well as in the resolution of cellular damage and inflammation.
Education and Training
- M.D., Johns Hopkins University, 1975
- Duke University Program in Environmental Health
- Advanced Immunobiology Traning Program for Surgeons
- Duke Resident Physician-Scientist Program- NHLBI
- Role of S-nitrosothiols in Akt1 signaling and pneumonia resolution
- Mitochondrial quality control and alveolar damage resolution after acute lung injury
- Oxidative tissue damage mitigation after exposure to HBO2 using FDA approved anti-epileptic drugs (AEDs)
- Interface of Mitochondrial Quality Control and Immune Activation in Heart Transplant
- Interdisciplinary Training Program in Lung Disease
- The role of Pdgfra+ fibroblasts in lung fibrosis and alveolar homeostasis
- A Phase II Study of Inhaled Carbon Monoxide for the Treatment of ARDS
- Critical Molecular Targets for the Toxic Effects of Hyperbaric Oxygen and a Novel Pharmacological Approach for Preventing Acute Toxicity