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Research interests

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.

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Projects 1994 2000

ENDOGENOUS OPIOID SYSTEMS AND HEART DEVELOPMENT

McLaughlin, P.

National Institutes of Health

1/1/9412/31/00

Project: Research projectResearch Project

Opioid Analgesics
Naltrexone
Intercellular Signaling Peptides and Proteins
Opioid Receptors
Autoradiography

Research Output 1976 2018

Autoimmune Experimental Encephalomyelitis
Naltrexone
Interleukin-10
Multiple Sclerosis
Opioid Analgesics
4 Citations
Encephalomyelitis
Autoimmune Experimental Encephalomyelitis
Enkephalins
Opioid Analgesics
Intercellular Signaling Peptides and Proteins
3 Citations

Featured Article: Serum [Met5]-enkephalin levels are reduced in multiple sclerosis and restored by low-dose naltrexone

Ludwig, M. D., Zagon, I. & McLaughlin, P., Sep 1 2017, In : Experimental Biology and Medicine. 242, 15, p. 1524-1533 10 p.

Research output: Contribution to journalArticle

Naltrexone
Enkephalins
Multiple Sclerosis
Opioid Analgesics
Intercellular Signaling Peptides and Proteins

Selective opioid growth factor receptor antagonists based on a stilbene isostere

Stockdale, D. P., Titunick, M. B., Biegler, J. M., Reed, J. L., Hartung, A. M., Wiemer, D. F., McLaughlin, P. & Neighbors, J., Jan 1 2017, In : Bioorganic and Medicinal Chemistry. 25, 16, p. 4464-4474 11 p.

Research output: Contribution to journalArticle

Stilbenes
Amides
Isomers
Opioid Analgesics
Intercellular Signaling Peptides and Proteins
2 Citations

Topical Naltrexone is a Safe and Effective Alternative to Standard Treatment of Diabetic Wounds

McLaughlin, P., Cain, J., Titunick, M. B., Sassani, J. & Zagon, I., Sep 1 2017, In : Advances in Wound Care. 6, 9, p. 279-288 10 p.

Research output: Contribution to journalArticle

Naltrexone
Wounds and Injuries
Diabetic Foot
Platelet-Derived Growth Factor
Mast Cells