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Sun-Kyeong Lee, Ph.D.

Academic Title
Associate Professor of Medicine
UConn Center on Aging

Education
Postdoctoral Fellow. University of Connecticut Health Center, Farmington, CT; Endocrinology
Ph.D. University of Connecticut, Storrs, CT; Physiology/Endocrinology
MS. Korea University, Seoul, Korea; Animal Physiology/Entomology
BS.  Korea University, Seoul, Korea; Biology

Awards
NIA Summer Institute; NIHNIA (2010)
Mazess Research Grant Award from National Osteoporosis Foundation (2002)
Doctoral Dissertation Fellowship Award:  University of Connecticut (1990)

A description of area of interest:
1. Understanding the role of macrophage migration inhibitory factor (MIF) in osteoclastogenesis. MIF plays an important role in systemic as well as local inflammatory and immune responses. However, the precise role of MIF in the regulation of normal and abnormal bone metabolism has not been fully defined.  Specific studies ongoing in my lab include the examination if MIF acts through a putative receptor CD74 and co-receptor (CD44) in osteoclastogenesis and the role of MIF in osteoclast fusion process using MIF knockout, CD74 knockout and CD44 knockout mouse models. We are particularly interested in the role of MIF in osteoclast precursor population and differentiation including fusion process of multinucleated osteoclastogenesis.

2. Role of interleukin-7 (IL-7) in bone.  IL-7 is a cytokine to be involved in the regulation of hematopoiesis, which primarily acts on the lymphoid cell (B and T lymphocytes) compartment of the immune system. We are examining the local effect of IL-7 in osteoclastogenesis as well as bone mass using targeted overexpression of IL-7 in osteoblasts. In addition using IL-7 knockout mouse model, we are developing the role of T or B cells in bone marrow compartment in osteoclastogenesis and how alteration in bone mass occurs in response to local IL-7 overexpression in IL-7 KO mice. We are also interested in examining the possible role of IL-7 in osteoblastogenesis in these mouse models.

3. Role of CD97 in osteoclastogenesis. CD97 is a member of the epidermal growth factor (EGF) seven-span transmembrane (7TM) subfamily of adhesion G protein-coupled receptors (GPCRs). Different from other membrane proteins of these subfamilies, CD97 possesses several EGF-like domains at the large N-terminal extracellular domain suggesting a potential function associated with adhesion. However, the presence of seven transmembrane domains with homology to GPCRs leads to the speculation that may also acts as cell surface receptor to transduce signals across the cell membrane.  In mice, CD97 is detected in most myeloid cells and variable portions of lymphocytes including T and B cells, and NK cells. Despite all data regarding the expression of CD97 in human and mice, the precise role of CD97 in the regulation of normal and abnormal bone metabolism has not been fully defined. We are interested in the possible role of CD97 and its interaction with its known ligand, CD55 in osteoclastogenesis.

A description of lab rotation projects:
Our lab studies osteoclast biology with specific interest in the role of MIF and IL-7 in bone formation and resorption. Models range from cell cultures to transgenic mice. Possible student projects include the following:

1. Role of MIF in osteoclast precursor population in bone marrow.  This study involves isolation of highly purified osteoclast precursors from bone marrow by FACS sorting and examination of genes by microarray analysis. Examination of signaling related genes identified by microarray analysis by MIF treatment needs to be confirmed by real-time RT PCR and/or western blot analysis. Signaling pathways in the induction of expression will be examined.

2. Bone phenotype analysis of CD74/CD44 knockout mice.  This study involves examination of bone phenotype by microCT and histomorphometric analyses, osteoclast and osteoblast formation assay, flow cytometric analysis and bone resorption pit assay.

3. Role of MIF in osteoclast fusion process. Highly purified FACS sorted osteoclast precursor cells will be utilized and examined if MIF alters the fusion process using time-lapse images, overexpression of fusion related gene expression and cell migration assay.

4. Role of CD97 and CD55 in osteoclastogenesis using CD97 KO mice. This study involves the examination of bone phenotype these mice models and its signaling mechanism by which CD97 contributes to osteoclastogenesis.

Selected Publications
Won, H. Y., S. H. Mun, B. Shin, S. K. Lee, 2016. Contradictory role of CD97 in basal and tumor necrosis factor α-induced osteoclastogenesis in vivo. Arthritis Rheumatol. 2015 Dec 14. doi: 10.1002/art.39538. [Epub ahead of print].

Canalis, E., L. Schilling, S.-P. Lee, S. K. Lee, S. Zanotti, 2016. Hajdu Cheney mouse mutants exhibit osteopenia, increased osteoclastogenesis, and bone resorption. J. Biological Chemistry, 2015 Dec 1. pii: jbc.M115.685453. [Epub ahead of print].

Zheng, X., S. K. Lee, O. K. Chun, 2016. Soy Isoflavones and Osteoporotic Bone Loss: A Review with an Emphasis on Modulation of Bone Remodeling. Journal of Medicinal Food. December 2015, ahead of print.

Book Chapters
Osteoimmunology textbook chapter entitled “The role of sex steroids in the effects of immune system on bone” Elsevier, 2015 in press

Current Grants
Title: Role of miR29 in osteoclastogenesis. 06/01/15-05/31/2020
This study is to examine the role of microRNA29 in osteoclastogenesis.  We will be utilizing sponge mice, which inhibit miR29 expression in osteoclast using TRAP promoter to investigate the effect of miR29.  We will also determine the bone phenotype of CD93KO and SRGAP2KO mice since these two genes are specific targets of miR29 in osteoclasts.
Role: Dual PI

Title: Anti-TNF-alpha approach to treat Osteogenesis Imperfecta. 04/01/15-03/31/17                                          
This study aims to examine the role of TNF-alpha in pathogenesis of osteogenesis imperfacta (OI) using OIM mouse models.  We will assess the frequency, phenotype, functional properties and NF-kB signaling pathway profile of osteoclast precursors in the bone marrow and periphery of OIM mice.
Role: Co-Investigator

Non-NIH Grants
USDA NIFA AFRI Seed Grant 12/15/2015-12/14/2017                                  
Title: Blackcurrant Prevents Osteoporosis Associated with Aging by Inhibiting Formation of Advanced Oxidation Protein Products.
USDA
This study aims to determine the effect of blackcurrant in lowering AOPP levels in plasma and bone during aging and to determine the mechanisms underlying the bone-protective action of blackcurrant.
Role: co-Investigator

Study sections non NIH
Research Councils UK (RCUK)

Presentations
Invited Podium Presentations at National/International Professional Conferences
2013                       The Role of CD44 in Osteoclastogenesis
                                The 1st Seoul Symposium on Bone Health, Seoul, Korea

Invited Podium Presentations at Scholarly Institutions
2014                       Role of Macrophage Migration Inhibitory Factor in Osteoclastogenesis
                                School of Medicine, University of Zagreb, Zagreb, Croatia

2013                       Role of Macrophage Migration Inhibitory Factor in Osteoclastogenesis
                                Department of Nutritional Science, University of Connecticut, Storrs, CT

Poster Presentation of Peer Reviewed Abstracts
2014       Black currant extract attenuates ovariectomy-induced bone loss in mice. Experimental Biology Annual Meeting, San Diego, CA
2013       miRNA-29 promotes osteoclastogenesis through regulation of osteoclast commitment and migration.
                 American Society for Bone and Mineral Research, Baltimore, MD

2013       CD97 expression on osteoclasts enhances osteoclastogenesis and regulates bone mass.  American Society for Bone and Mineral Research, Baltimore, MD
  
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