1. Extending the Scientific Legacy of Candace Pert, Ph.D.: Toward a model linking homeodynamic behavioral, physiological, and immune mechanisms with implications for disease progression

Abstract

Candace Pert died unexpectedly on 9-12-2013, leaving a substantial legacy of scientific discoveries. Her research on the dynamic information network by which stress can affect disease processes sought to link emotional phenomena to specific molecular targets, particularly neuropeptide receptors. She found that viruses encode multiple chemokine-like peptides which suppress innate immunity and facilitate viral entry, identifying the Peptide T sequence from HIV as an antagonist of HIV co-receptor CCR5. Pert and Ruff stabilized Peptide T analogs for candidate therapeutics which have anti-inflammatory and anti-viral effects. To date, the translation of behavioral and biomedical research findings into effective HIV interventions has followed separate routes. Ader’s recent research showed that behavioral conditioning linked to a biologically potent drug can induce the same physiological effects; thus significantly less of the drug is required. Logically, behavioral conditioning based on understanding key mechanisms, targets, signaling pathways, and/or biomarkers could synergize/maximize the effects of pharmacological therapies. Research on the clinically validated receptor targets described by the action of Peptide T converges on Temoshok’s findings from a 5-year study in 200 African-American HIV+ individuals that more adaptive, homeodynamic psychosocial/physiological responses to stressors enhanced the production of beta-chemokines which are CCR5 ligands. Pert’s work identifying viral analogs of presumptive endogenous neuropeptide ligands related to the VIP/PACAP/GHRH peptides suggest additional directions by which behaviors may effect release of peptide hormones from the ‘endogenous pharmacopeia’.