Email

dongsu.park@bcm.edu

Positions

Assistant Professor

Molecular and Human Genetics
Baylor College of Medicine

Assistant Professor

Pathology & Immunology
Baylor College of Medicine

Faculty Member

Center for Skeletal Medicine and Biology
Baylor College of Medicine

Faculty Member

The Rolanette and Berdon Lawrence Bone Disease Program of Texas
Baylor College of Medicine

Faculty Member

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 March 2; 10 (3): 259-72.
• 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.
• 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.
• 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.

Funding

Role of osteogenic stem/progenitors in bone regeneration and repair in vivo - #K01 AR061434 (PI)

(07/01/2012 - 06/30/2017) NIH/NIAMS

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

Grant funding from NIH/NIAMS

Defining Periosteal Skeletal Stem Cell Heterogeneity and Age-associated Change - #R21 AG064345 (MPI)

NIH/NIA

A new model for spatio-temporal coupling of bone formation and bone resorption governed by osteoclasts - #R61 AR078073 (MPI)

NIH/NIAMS