Title: Role of mitochondrial deacetylase Sirt3 in skeletal homeostasis
The central hypothesis of this project is that Sirt3 plays an essential role in the excessive bone resorption that occurs with old age or estrogen deficiency by stimulating Complex I activity and ATP production in osteoclast lineage cells. Three specific aims are proposed to address this hypothesis: 1) Determine whether deletion of Sirt3 in osteoclast lineage cells prevents the loss of bone mass caused by advancing age or estrogen deficiency, 2) Determine whether deletion of Sirt3 in osteoblast lineage cells impacts the loss of bone mass caused by advancing age or estrogen deficiency, and 3) Identify Sirt3 target proteins in osteoclasts that are responsible for their effects on mitochondrial function during osteoclast development.
Ha-Neui Kim, Ph.D., joined the UAMS Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases as an Assistant Professor in 2017. He joined the laboratory of Dr. Stavros C. Manolagas as a postdoctoral fellow in 2012 and begun several projects investigating age-related bone loss under the direct supervision of Dr. Maria Almeida. As part of these studies, he discovered that anti-aging FoxO transcription factors restrain osteoclastogenesis and bone resorption by attenuating H2O2 accumulation. His recent work led to the seminal finding that cellular senescence of osteoprogenitors and osteocytes causes age-related bone loss. The skills and knowledge he has acquired during his research on bone metabolism have laid the foundation for him to begin his work as a junior faculty member in the Division of Endocrinology. He was recognized for his work with a Young Investigator Award in 2013 and a Harold M. Frost Young Investigator Award in 2019, from the American Society for Bone and Mineral Research. The current goal of his study is to investigate the role of mitochondrial quality control in skeletal homeostasis.
Dr. Kim’s Mentors
Stavros C. Manolagas, M.D., Ph.D. is a Professor of Medicine and Orthopedics at UAMS with extensive expertise in bone biology, an outstanding publication and funding record, and a demonstrated ability to thrive as a productive physician-scientist. His research focus is on the impact of sex steroids on the skeleton.
Lee Ann MacMillan-Crow, Ph.D. is a Professor of Pharmacology and Toxicology at UAMS and an expert on oxidative stress with a strong record of R01 funding. She is also an experienced mentor that has worked extensively with young scientists and has guided many junior faculties through the various stages of promotion and tenure at UAMS.