Regis O’Keefe

Department of Orthopaedic Surgery

Washington University School of Medicine

Dr. O'Keefe specializes in musculoskeletal oncology and pursues research related to cartilage, skeletal development, and bone regeneration. He received his medical degree at Harvard Medical School and his PhD degree at the University of Rochester. Dr. O’Keefe completed an orthopedic oncology fellowship at Massachusetts General Hospital. Prior to his leadership role at Washington University, Dr. O’Keefe served as the chair of the Department of Orthopaedics at the University of Rochester.  He has chaired two standing NIH study sections, and served on the NIAMS Council and the NIH Council on Councils.  Dr. O’Keefe is past president of the Orthopaedic Research Society and the American Orthopaedic Association, the two leading academic orthopaedic organizations in the United States.    

“Targeting Dnmt3b and Abat in the Regulation of Osteoarthritis”

Osteoarthritis (OA) is a common disease, involving joints in the upper and lower extremities, including the TMJ.  While genetic signals associated with OA have been elusive, characteristics alterations in DNA methylation have been described.   DNA methyltransferase 3b (Dnmt3b) is highly expressed in normal articular cartilage, but expression is reduced in OA in both humans and mice.   In contrast, 4-aminobutyric acid transferase (Abat), a target of Dnmt3b methylation, is reciprocally regulated, and therefore increased in OA.  Our work has defined regulation of the Dnmt3b/Abat signaling access as a key regulator cartilage homeostasis and OA related pain.   Targeting Dnmt3b and Abat with nanoparticle mediated gene delivery is able to abate the development of OA and reduce pain related behaviors in mice.  Data suggests that signals downstream of Dnmt3b and Abat are involved in regulating joint inflammation following injury.