Giuliana E. Salazar-Noratto

BME Ph.D. Proposal

Date: Thursday, July 30th

Time: 8 am

Location: IBB 1128

Thesis committee

Robert E. Guldberg, Ph.D. (ME, Georgia Institute of Technology) (Advisor)

Greg Gibson, Ph.D. (Biology, Georgia Institute of Technology)

Clifton Willimon, M.D. (Children’s Orthopaedics of Atlanta) 

Nick J. Willett, Ph.D. (Orthopaedics, Emory University)

Johnna S. Temenoff, Ph.D. (BME, Georgia Institute of Technology)

Title: Elucidating the Pathophysiology of Degenerative Joint Disorders for the Prevention of Osteoarthritis

Abstract

Osteoarthritis (OA) is the most common form of musculoskeletal disability, affecting millions of people worldwide. It specially imposes a larger and longer-term burden in the healthcare system when it affects the working or pediatric population. Juvenile Osteochondritis Dissecans (JOCD) of the knee affects adolescent and young adults, and progresses to early onset OA. JOCD initially involves the formation of an avascular lesion in the subchondral bone with secondary effects in the overlaying articular cartilage. During late stages of this disorder, the lesion becomes unstable and the necrotic osteochondral fragment separates from the parent bone. The etiology of JOCD is not fully understood. Previous research has been primarily limited to retrospective clinical studies, thus hampering the understanding and the creation of novel therapeutics for this disorder and its progression to OA.

The objective of this thesis is to elucidate the pathophysiology of JOCD and to explore venues to prevent its progression to OA. We will also study treatment options when OA has already developed. With iPSC technology, we will investigate the pathogenesis of JOCD as well as establish a new in vitro disease model to test potential pharmacological cures for JOCD. We will also develop a small preclinical animal model of JOCD with the ability to emulate early stages of the disorder in order to test novel treatment options, as well as tailor current clinical approaches. Successfully treating JOCD patients at an earlier timepoint should prevent the fragmentation of osteochondral bodies in late stages and early onset of OA in these young patients. For later stages of JOCD or cases in which OA has started to develop, it is imperative that the cartilage is treated along with the bone. Therefore, we will also evaluate the mechanisms of joint degeneration and response to treatment in a well-established OA animal model. Our goal is to elucidate the pathway by which cartilage regenerates in cases where there is an onset of OA. Ultimately, this project will advance our understanding of the mechanisms of joint degenerative joint disorders (JOCD and OA) and potential treatments for the preservation and regeneration of articular cartilage.