John D. Piganelli, PhD

  • Associate Professor, Department of Surgery
  • Associate Professor, Department of Immunology

Education & Training

  • Postdoc, University of Colorado Health Sciences Center / Barbara Davis Center for Childhood Diabetes
  • PhD, Oregon State University
  • BS, Colorado State University

Research Interests

Dr. Piganelli's group has been involved in studying immunology and autoimmunity; more specifically type 1 diabetes (T1D). His  work primarily focuses on the role of oxidative stress and free radical generation and how it leads to secondary inflammation, since the majority of pathological conditions have an inflammatory component. Also, these redox reactions are critical for synergizing the innate and adaptive immune response, and exploitation of these reactions can modulate immune function in a variety of diseases. He has studied these interaction in both human islets isolated from cadaveric donors as well as in animal models of T1D like the NOD mouse. Furthermore, his group’s work has demonstrated that modulation of redox dependent signaling can have a positive effects on controlling aberrant immune responses, as well as the protection and preservation of organs and tissue for transplantation.  Dr. Piganelli's group has utilized a manganese porphyrin oxidoreductase (MnTE-2-PyP5+, MnP) as a potential immunoregulatory therapy for type 1 diabetes. MnP has previously been shown to modulate diabetogenic immune responses through decreases in proinflammatory cytokine production from antigen-presenting cells and T cells and to reduce diabetes onset in nonobese diabetic mice. They also demonstrated that MnP treatment can act beyond our previous reports of controlling inflammatory mediators. MnP treatment marked effects on metabolic switch of T cells during activation by impeding the switch of T cells from oxidative phosphorylation to glycolysis, a critical step for full T cell activation. This effect has an impact on activated T cell transition from activation to effector function. These alterations occur because of increased tricarboxylic acid cycle aconitase enzyme efficiency and are not due to changes in mitochondrial abundance. MnP treatment also displays decreased aerobic glycolysis, thus promoting reduced activation of immune cell proliferation. This work highlights the importance of redox signaling by demonstrating that modulation of reactive oxygen species can supplant complex downstream regulation, thus affecting metabolic programming toward aerobic glycolysis. MnP treatment promotes metabolic quiescence, impeding diabetogenic autoimmune responses by restricting the metabolic pathways for energy production and affecting anabolic processes necessary for cell proliferation. These findings may allow of an innovative way of controlling aberrant immune response in a selective way.

The lab is also interested in studying how environmental triggers affect the progression of autoimmune disease like type 1 diabetes. They have begun to dissect the role of endoplasmic reticulum stress (ER-stress) in beta cells as a result of normal protein production and how this ER-stress may lead to an aberrant immune response in those individuals that are genetically predisposed to autoimmunity.