Positions
- Assistant Professor
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Molecular and Human Genetics
Baylor College of Medicine
- Faculty Member
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Graduate Program in Development, Disease Models & Therapeutics
Baylor College of Medicine
- Faculty Member
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Center for Skeletal Medicine and Biology & BDPT
Baylor College of Medicine
- Faculty Member
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Graduate Program in Genetics and Genomics
Baylor College of Medicine
Education
- PhD from Baylor College of Medicine
- 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 (Park et al, Cell Stem Cell 2012). More recently, we discovered adult SSC heterogeneity and a long-term repopulating SSC subset present in periosteum (outer layer of bone) in vivo. These periosteal SSCs are critical for periosteal (outer) bone maintenance, specifically express CCL5 receptors, CCR5, and have a unique CCL5-dependent migratory mechanism required for bone injury repair (Ortinau et al, Cell Stem Cell, 2019). We now aim to address functional heterogeneity and epigenetic regulation 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 are a key component for the HSC niche and are essential to protect HSCs from external stress. However, due to the lack of in vivo HSC tracking model, 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. Recently, we generated novel animal models to selectively label endogenous HSCs and SSCs and found a clear displacement of HSCs away from CXCL12-expressing niche cells upon interferon treatment. We are now elucidating the mechanisms by which niche cells regulate HSCs and understanding how perturbations to these interactions can promote disease states such as hematopoietic aging and malignancies.
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 "Endogenous bone marrow MSCs are dynamic, fate-restricted participants in bone maintenance and regeneration.." Cell Stem Cell. 2012 Mar 2;10(3):259-72. Pubmed PMID: 22385654
- Deveza L, Ortinau L, Lei K, Park D. "Comparative analysis of gene expression identifies distinct molecular signatures of bone marrow- and periosteal-skeletal stem/progenitor cells.." PLoS ONE. 2018;13(1):e0190909. Pubmed PMID: 29342188
- Ortinau CL, Wang H, Lei K, Deveza L, Jeong Y, Hara Y, Grafe I, Rosenfeld S, Lee D, Lee B, Scadden DT, Park D "Identification of Functionally Distinct Mx1+αSMA+ Periosteal Skeletal Stem Cells.." Cell Stem Cell. 2019;25(6):784-796. Pubmed PMID: 31809737
- Scaramozza A, Park D, Kollu S, Beerman I, Sun X, Rossi DJ, Lin CP, Scadden DT, Crist C, Brack AS. "Lineage Tracing Reveals a Subset of Reserve Muscle Stem Cells Capable of Clonal Expansion under Stress.." Cell Stem Cell. 2019;26(6):944-957. Pubmed PMID: 31006621
- Florez MA, Matatall KA, Jeong Y, Ortinau L, Shafer PW, Lynch AM, Jaksik R, Kimmel M, Park D*, King KY* "Interferon Gamma Mediates Hematopoietic Stem Cell Activation and Niche Relocalization through BST2." Cell Reports. 2020;33:108530 (*Corresponding Authors). Pubmed PMID: 33357430
- Park D, Lapteva N, Seethammagari M, Slawin KM, Spencer DM "An essential role for Akt1 in dendritic cell function and tumor immunotherapy.." Nature Biotechnology. 2006;24(12):1581-90. Pubmed PMID: 17143278
- Jeong Y, Park D. "Targeting periosteal SSCs for aged bone defects." Aging (Albany NY). 2020;12(4):3124-3125. Pubmed PMID: 32090980
- Solidum JGN, Jeong Y, Heralde F 3rd, Park D "Differential regulation of skeletal stem/progenitor cells in distinct skeletal compartments.." Front Physiol. 2023 Feb;14:1137063. Pubmed PMID: 35980285
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
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