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Email

dongsu.park@bcm.edu

Positions

Associate Professor

Molecular and Human Genetics
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Faculty Member

Graduate Program in Development, Disease Models & Therapeutics
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Faculty Member

Center for Skeletal Medicine and Biology & BDPT
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Faculty Member

Graduate Program in Genetics and Genomics
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Education

PhD from ²ÝÁñÉçÇøÈë¿Ú

01/2007 - Houston, Texas United States

Post-Doctoral Fellowship at Massachusetts General Hospital & Harvard Stem Cell Institute

01/2013 - Cambridge, Massachusetts United States

Professional Interests

• Molecular and cellular biology of mesenchymal/skeletal stem cells in tissue regeneration and cancer
• Stem cell imaging and tracking in living animals

Professional Statement

The main interest of my lab is to understand the in vivo identity and pathophysiological function of stem/progenitor cells in bone regeneration and repair and to develop better treatment methods for devastating bone and connective tissue disorders. Adult skeletal stem cells (SSCs) are critical for life-long maintenance and regeneration of bone and bone marrow. These cells are also critical in the bone marrow microenvironment to regulate hematopoiesis with likely participation in leukemia and cancer metastasis. However, the in vivo characteristics and function of SSCs remain fundamental and still unanswered questions. To address these questions, we have developed a new strategy utilizing genetic pulse-chase models and advanced intravital imaging technology. Using this approach, we defined the lifespan and unexpectedly short-term recycling of osteoblasts in vivo. Further, long-term maintenance of osteogenic cells comes from lineage-restricted skeletal stem/progenitor cells (Cell Stem Cell 2012). In addition, we discovered adult SSC heterogeneity and a long-term repopulating SSC subset present in periosteum (outer layer of bone) in vivo. Notably, these periosteal SSCs are critical for periosteal (outer) bone maintenance and require a unique CCL5-dependent migratory mechanism and LRP1 activation for bone injury repair (Cell Stem Cell 2019, JCI Insight 2024). We now aim to address functional heterogeneity, novel epigenetic and suppressive mechanism of SSCs in the context of skeletal aging and to explore the clinical relevance of these cells in bone disorders, injuries and cancer bone metastasis.

Bone and bone marrow provide a specialized microenvironment (HSC niche) for the maintenance and function of HSCs. SSCs/BMSCs are key components for the HSC niche and therefore, HSCs and SSCs are mutually important for their protection from external stress. However, due to the lack of in vivo HSC/SSC tracking models, how stress signals control endogenous HSCs and their niche interaction is largely unknown. We previously found that bone marrow stresses regulate the HSC lineage commitment and identified important factors in myeloid/erythroid-lineage differentiation under marrow stress conditions (Cell Reports 2020). Recently, we generated novel animal models to selectively label endogenous HSCs and SSCs and found a clear displacement of HSCs away from CXCL12+ BMSCs upon interferon treatment. We are now elucidating whether SSCs in bone diseases regulate HSCs and how perturbations to these interactions can promote degenerative bone and hematopoietic disease states.

My laboratory is also interested in the identity and function of stem cell populations in non-skeletal tissues such as muscle and tendon. Our recent studies demonstrated that the adult muscles and tendons contain a discrete population of stem cells that appear postnatally and undergo clonal expansion under severe stress and injury. However, their cellular origin and mechanisms that govern tendon and connective tissue regeneration and repair remain unknown. We work on these important questions using a variety of genetic, immunologic and microscopic technologies with the goal of identifying molecules and mechanisms that regulate stem cells of different tissue origin. These studies will elucidate fundamental aspects of skeletal tissue regeneration and may lead to the development of new regenerative medicine strategies.

Websites

Selected Publications

• Park D, Spencer JA, Koh BI, Kobayashi T, Fujisaki J, Clemens TL, Lin CP, Kronenberg HM, Scadden DT "." Cell Stem Cell. 2012 Mar 2;10(3):259-72. Pubmed PMID:
• Deveza L, Ortinau L, Lei K, Park D. "." PLoS ONE. 2018;13(1):e0190909. Pubmed PMID:
• Ortinau CL, Wang H, Lei K, Deveza L, Jeong Y, Hara Y, Grafe I, Rosenfeld S, Lee D, Lee B, Scadden DT, Park D "." Cell Stem Cell. 2019;25(6):784-796. Pubmed PMID:
• Scaramozza A, Park D, Kollu S, Beerman I, Sun X, Rossi DJ, Lin CP, Scadden DT, Crist C, Brack AS. "." Cell Stem Cell. 2019;26(6):944-957. Pubmed PMID:

Funding

Defining periosteal skeletal stem cells and novel migration mechanisms in bone regeneration and repair in vivo - #R01 AR072018 (PI)

Grant funding from NIH/NIAMS

Skeletal progenitor cell dysfunction during development and repair in osteogenesis imperfecta - #R01DE031288 (PI)

Grant funding from NIH/NIDCR

WNT1 Function in Stem Cells in Osteogenesis Imperfecta and Craniofacial-Skeletal Tissues - #R01DE031162 (MPI)

Grant funding from NIH/NIDCR