Understanding Oxidative Stress through Reverse Engineering

There is growing evidence that oxidative stress plays a role in human maladies that range from bowel diseases to mental health disorders.  However, the current understanding of oxidative stress is incomplete and still evolving.  For instance, despite persistent epidemiological evidence of the health benefits of diets rich in antioxidants, interventional trials with antioxidants have been largely unsuccessful.  Currently, there is intense study to resolve the underlying chemical and biological mechanisms of oxidative stress and also how these mechanisms act across the body’s various systems (e.g., the immune, digestive and nervous systems). IBBR researchers are developing new methodologies that enlist the diverse capabilities of various technologies to access and analyze the chemical information of complex biological samples (e.g., blood) to discern robust signatures related to oxidative stress.

One collaboration with electrical engineers from the University of Maryland and Ben-Gurion University (Israel) and clinicians at the Maryland Psychiatric Research Center aims to integrate technology to manage schizophrenia.  Schizophrenia is a complex and poorly understood neuropsychiatric disorder affecting 1% of the population and growing evidence implicates oxidative stress as a factor in schizophrenia.  IBBR researchers have shown that the assembly of polysaccharide films containing carbon nanotubes can confer electrode sensors with properties that enable trace levels of the antipsychotic drug clozapine to be detected in patient serum.  This, and related, developments will enable the use of technology (e.g., portable devices) to better understand, manage and personalize therapies for patients and families suffering from such mental health disorders.

A second collaboration with the University of Naples and the US Food and Drug Administration is applying electrochemical reverse engineering methodologies to the study of melanin which is a ubiquitous phenolic-based pigment in the skin and brain.  Melanin has been linked to melanoma and neurological disorders (e.g., Parkinson’s disease), yet the underlying mechanisms are uncertain.  IBBR researchers have discovered that melanins possess redox-activity and can exchange electrons with common biological oxidants (e.g., O2) and reductants (e.g., ascorbate), as well as undergo redox-cycling interactions with environmental toxins (e.g., pesticides), bacterial virulence factors, and therapeutics.  These observations indicate that melanins may play a previously unrecognized role in redox homeostasis and oxidative stress.