Richard F. Loeser, Jr., MD

Director, UNC Thurston Arthritis Research Center
Herman and Louise Smith Distinguished Professor of Medicine, Division of Rheumatology, Allergy & Immunology

Specialty Areas: cartilage cell biology, redox regulation of cell signaling, aging and the development of osteoarthritis, integrin function in cartilage, vitamin K-dependent proteins in the joint, osteoarthritis biomarkers and phenotypes, osteoarthritis interventions including exercise and weight loss

Chronology: Virginia Tech, 1977-1980; MD, West Virginia University, 1984; Residency, Wake Forest Baptist Medical Center, 1984-1987; Fellowship, Wake Forest Baptist Medical Center, 1987-1989; Instructor, Internal Medicine, Bowman Gray School of Medicine, 1989-1991; Assistant Professor of Internal Medicine (Rheumatology), Bowman Gray School of Medicine, 1991-1996; Associate Professor of Internal Medicine (Rheumatology), Wake Forest University School of Medicine, 1996-1999; Associate Professor of Internal Medicine (Rheumatology), Rush Medical College, 1999-2002; Professor of Internal Medicine (Rheumatology), Rush Medical College, 2002-2005; Professor of Internal Medicine (Molecular Medicine and Rheumatology, Professor of Orthopedic Surgery and Head, Section of Molecular Medicine, Wake Forest University School of Medicine; 2005-2014; Professor, Wake Forest University Translational Science Institute., 2005-2014; Director of Translational Research, The Sticht Center on Aging, Wake Forest University School of Medicine, 2008-2014; Distinguished Professor of Medicine (Rheumatology), Director of Basic and Translational Research, Thurston Arthritis Research Center, University of North Carolina-Chapel Hill, 2014-2017, Director, Thurston Arthritis Research Center, 2017-Present.

Description of research and/or clinical interests: Dr. Loeser’s primary research goal is to discover the basic mechanisms relevant to joint tissue destruction in osteoarthritis. Osteoarthritis (OA) is the leading cause of pain and disability in older adults. A better mechanistic understanding of OA is needed in order to develop interventions that can slow or stop disease progression before advanced joint tissue destruction occurs.

Dr. Loeser’s lab uses a combination of in vitro experiments using human joint tissue cells and in vivo experiments in rodent models to study cell signaling pathways that regulate anabolic and catabolic activity responsible for joint tissue remodeling and destruction. The lab is particularly interested in determining how reactive oxygen species regulate chondrocyte signaling downstream of integrins, cytokines and growth factors through the oxidation of specific cysteine residues in kinases and phosphatases as well as other intracellular proteins. The lab is studying how oxidative stress that occurs with aging and joint injury can alter the activity of these signaling pathways.

Dr. Loeser’s clinical research interest is in exercise and weight loss interventions for knee OA as well as the potential role of gut microbiota in OA.  He has been involved in OA biomarker studies that have included metabolomics work and recently in a multidisciplinary effort to define OA phenotypes.

 

Selected Bibliography:

Selected Integrin studies

a. Loeser RF, Forsyth CB, Samarel, A, Im H-J. Fibronectin-fragment activation of proline-rich tyrosine kinase PYK2 mediates integrin signals regulating collagenase-3 expression by human chondrocytes through a protein kinase C-dependent pathway. J Biol Chem 2003;278:24577-24585. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12730223

b. Long DL, Willey JS, Loeser RF. Rac1 is required for matrix metalloproteinase-13 production by chondrocytes in response to fibronectin fragments. Arthritis Rheumatol 2013; 65: 1561-1568.  http://www.ncbi.nlm.nih.gov/pubmed/23460186

c. Huang G, Chubinskaya S, Liao W, Loeser RF. Wnt5a induces catabolic signaling and matrix metalloproteinase production in human articular chondrocytes. Osteoarthritis and Cartilage 2017: 25:1505-1515. http://www.ncbi.nlm.nih.gov/pubmed/28587781

d. Wood ST, Long DL, Reisz JA, Yammani RR, Burke EA, Klomsiri C, Poole LB, Furdui CM, Loeser RF. Cysteine-mediated redox regulation of cell signaling in chondrocytes stimulated with fibronectin fragments. Arthritis Rheumatol 2016; 68;117-126. http://www.ncbi.nlm.nih.gov/pubmed/26314228

e. Nelson KJ, Bolduc JA, Wu H, Collins JA, Burke EA, Reisz JA, Klomsiri C, Wood ST, Yammani RR, Poole LB, Furdui CM, Loeser RF. H2O2 oxidation of cysteine residues in c-Jun N-terminal kinase 2 (JNK2) contributes to redox regulation in human articular chondrocytes. J Biol Chem (in press) http://www.ncbi.nlm.nih.gov/pubmed/30190325


Selected Aging and Oxidative Stress studies

a. Yin W, Park J-I, Loeser RF. Oxidative stress inhibits insulin-like growth factor-1 induction of chondrocyte proteoglycan synthesis through differential regulation of PI-3 kinase-Akt and MEK-ERK MAPK signaling pathways. J Biol Chem 2009; 284:31972-31981. http://www.ncbi.nlm.nih.gov/pubmed/19762915

b. Greene MA, Loeser RF. Function of the chondrocyte PI-3 kinase-Akt signaling pathway is stimulus dependent. Osteoarthritis Cartilage 2015; 23:949-56. http://www.ncbi.nlm.nih.gov/pubmed/25659655

c. Loeser RF, Collins JA, Diekman BO. Ageing and the pathogenesis of osteoarthritis. Nat Rev Rheumatol 2016;12:412-420. http://www.ncbi.nlm.nih.gov/pubmed/27192932

d. Collins JA, Wood ST, Nelson KJ, Rowe MA, Carlson CS, Chubinskaya S, Poole LB, Furdui CM, Loeser RF. Oxidative stress promotes peroxiredoxin hyperoxidation and attenuates pro-survival signaling in aging chondrocytes. J Biol Chem 2016; 291:6641-6654. http://www.ncbi.nlm.nih.gov/pubmed/26797130

e. Bolduc JA, Collins, JA, Loeser RF. Reactive oxygen species, aging, and articular cartilage homeostasis. Free Radic Biol Med (in press) http://www.ncbi.nlm.nih.gov/pubmed/30176344

Complete list of published work in My Bibliography:

http://www.ncbi.nlm.nih.gov/myncbi/browse/collection/40357716/?sort=date&direction=descending