Dr. Patricia McLaughlin’s research focuses on the Opioid Growth Factor (OGF) – OGF receptor (OGFr) pathway and mechanisms of action in homeostasis and disease. Early collaborative work with Dr. Ian Zagon resulted in the identification of [Met5]-enkephalin as the endogenous ligand for the OGF-OGFr pathway. Subsequently, a new nuclear-associated receptor was identified and termed OGFr. One group in the laboratory has characterized and cloned the OGFr gene in human, mouse and rat. Protein chemistry studies, along with structural biology, determined that the OGFr is a uniquely unstructured nuclear receptor. The mechanism of action was determined to involve inhibition of DNA synthesis with the specific mechanistic pathway involving upregulation of cyclin-dependent inhibitory kinases p16 and p21. OGF action is receptor-mediated, reversible, and not associated with apoptosis/necrosis. OGF is tissue non-specific and has been identified in proliferating cells and tissues derived from all 3 dermal layers.

Currently, the lab’s work is translational, focusing on disease-based pathways that are characterized by a perturbation in the OGF-OGFr axis. Consequences of receptor blockade of the OGF-OGFr axis are being studied with an emphasis on the etiology and treatment of complications (e.g., delayed wound healing, dry eye, impaired bone composition) arising from long-term diabetes (Type 1 or Type 2). These investigations (humans and animal models) focus on treatment options and utilize confocal microscopy, animal surgery, immunohistochemistry and tissue culture.

In another series of studies, the lab is testing the hypothesis that down-regulation of the inhibitory OGF peptide plays a role in multiple sclerosis and other autoimmune diseases. The lab is also currently validating serum biomarkers and cytokine expression profiles that correspond to changes in behavior and MRI imaging that may be related to disease progression and response to therapy. The clinical and animal research is both qualitative and quantitative in design and is supported by NIH, ADA, TSF (PA) and foundations.