Sung Kee Seanna Yoon

Sung-Hee Seanna Yoon, Immunology

Student’s full name: Sung-Hee Seanna Yoon
Supervisor’s full name and title: Dr. Jane Mitchell (Dept of Pharmacology and Toxicology) and Dr. Marc Grynpas (Lunenfeld-Tanenbaum Research Institute)
PhD thesis (title and brief overview): Potential therapies for bone health in glucocorticoid-treated Mdx mouse model of Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy (DMD) is an X-linked genetic disease, affecting 1 in 3500 boys. It is a progressive disease, presented with chronic inflammation, severe necrosis and degeneration of muscle. There is no cure, and most patients receive long-term glucocorticoid therapy to delay the disease progression.

In addition to their muscle phenotype, DMD patients also suffer from bone fragility due to chronic inflammation in muscle, suboptimal vitamin D levels, and lack of mechanical loading from the muscle on bone. Their bone health is even further compromised by the use of long-term glucocorticoids, which are known to significantly suppress osteoblasts, resulting in osteoporosis.

For my PhD project, we wanted to 1) identify the roles of vitamin D insufficiency/deficiency in bone health, with or without glucocorticoids, using the Mdx mouse model of DMD, 2) to determine the effectiveness of using intermittent PTH, or 3) growth hormone as bone anabolic agents, as glucocorticoids dramatically suppress bone turnover. These bone treatments were concurrently done with glucocorticoids to ameliorate the development of glucocorticoid-induced osteoporosis, during rapid bone growth to mimic young DMD boys receiving the glucocorticoid treatment.

We found that suboptimal 25-(OH)D (lower than 50nmol/L) did not have significant effects on musculoskeletal health in growing Mdx mice, regardless of glucocorticoid treatment. However, intermittent PTH treatment improved the glucocorticoid-induced cortical bone loss, as well as dystrophic muscle-driven osteopenic phenotype in trabecular bone. PTH treatment also maintained beneficial effects of glucocorticoids on muscle or further exerted positive effects on dystrophic muscle phenotype. Growth hormone treatment had minimal effects on bone microarchitectures, but significantly improved biomechanical properties in both cortical shaft and vertebrae. On the top of the beneficial effects of glucocorticoids on dystrophic muscle, growth hormone treatment further enhanced muscle function and histomorphometry by reducing fiber size variation and percentage of fibers with central nuclei. This study suggested PTH and growth hormone as potential treatments for musculoskeletal health in glucocorticoid-treated DMD boys during growth.

My research interests lie in the field of bone biology and mineral metabolism. As a graduate student, my research focused on examining the mineral metabolism and musculoskeletal effects of hormonal therapies (vitamin D, parathyroid hormone (PTH), and growth hormone) in the mouse model of Duchenne Muscular Dystrophy. I have published five first-author peer-reviewed articles and received numerous prestigious awards including Ontario Graduate Scholarship and Young Investigator Award from the American Society of Bone and Mineral Research.

From my graduate training at University of Toronto, I gained substantial experience in endocrinology and pharmacology, as well as bone biology. Considering that the kidney and bones are the key organs in mineral metabolism and the main targets of PTH, my research interests are extended to understand the downstream signaling pathway of PTH in kidney. By elucidating the role of salt-inducible kinases in renal PTH action, together with their effects on bone health as well as mineral homeostasis, I will be able to demonstrate its therapeutic potential for patients with chronic kidney disease associated mineral and bone disorder (CKD-MBD). For this work, I received the Canadian Institutes of Health Research (CIHR) Postdoctoral Fellowship.

I am currently a Postdoctoral Fellow in the Endocrine Unit at the Massachusetts General Hospital-Harvard Medical School with Drs. Marc Wein & Michael Mannstadt. We are investigating the role of salt-inducible kinases (SIKs) in renal parathyroid hormone (PTH) signaling, and their effects on phosphate regulation and Cyp27b1 expression in kidney.

Alum of Sung-Hee Seanna Yoon, Immunology