Dr. Fuchs' overarching goal is to translate his research findings to improve the survival rates of patients with septic shock, and he conducts his investigations from two perspectives.
In the first, he seeks to define the role of disrupted iron homeostasis in altering immunity and survival in sepsis. To accomplish that, he and his colleagues are working to validate an iron-overloaded murine model system to determine the role of in vivo iron in bacterial infection and sepsis. In their sepsis model, the investigators monitor survival while measuring iron overload and immune-specific markers.
The second aspect of Dr. Fuchs' research translates directly to patient care. He seeks to define the role of the transcription factor Nrf-2 (which was only recently identified) in regulating immunity, inflammation and redox balance (the balance between oxidants and antioxidants) under conditions of septic shock in critically ill adults. Dr. Fuchs and his colleagues hypothesize that diminished Nrf2 activity in patients with septic shock is associated with increased morbidity and mortality secondary to a disruption in the normal immune response to infection. They hypothesize that increasing Nrf2 activity in peripheral blood mononuclear cells (PBMCs) and neutrophils of patients with septic shock would protect against deregulation of the innate immune response by maintaining the redox balance.
As principal investigator, Dr. Fuchs is leading the interdisciplinary team conducting a prospective cohort study in which they are isolating PBMCs and neutrophils from adult patients in the intensive care unit who are in septic shock; they plan to measure Nrf2 activity to determine its impact on mortality, length of stay, vasopressor days and ventilator days. In addition, they intend to evaluate the potency of an Nrf2 activator to express more Nrf2 activity ex vivo using PBMCs and neutrophils of patients with septic shock.
- Thimmulappa RK, Fuchs RJ, Malhotra D, Scollick C, Traore K, Bream JH, Trush MA, Liby KT, Sporn MB, Kensler TW, Biswal S. “Preclinical evaluation of targeting the Nrf2 pathway by triterpenoids (CDDO-Im and CDDO-Me) for protection from LPS-induced inflammatory response and reactive oxygen species in human peripheral blood mononuclear cells and neutrophils.” Antioxid Redox Signal. 2007 Nov;9(11):1963-70.
- Fuchs RJ, Levin J, Tadel M, Merritt W. “Perioperative coagulation management in a patient with afibrinogenemia undergoing liver transplantation.” Liver Transpl. 2007 May;13(5):752-6.
- Fuchs RJ, Berenholtz SM, Dorman T. “Do intensivists in ICU improve outcome?” Best Pract Res Clin Anaesthesiol. 2005 Mar;19(1):125-35. Review.
- Xu X, Pin S, Gathinji M, Fuchs R, Harris ZL. “Aceruloplasminemia: an inherited neurodegenerative disease with impairment of iron homeostasis.” Ann N Y Acad Sci. 2004 Mar;1012:299-305. Review.
- Fuchs RJ, Lee WA, Seubert CN, Gelman S. “Transient paraplegia after stent grafting of a descending thoracic aortic aneurysm treated with cerebrospinal fluid drainage.” J Clin Anesth. 2003 Feb;15(1):59-63.
Dr. Ralph Fuchs' Lab