Dongsu Park Lab

The Dongsu Park Lab’s research focuses on 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. While adult skeletal stem cells (SSCs) are critical for life-long maintenance and regeneration of bone and bone marrow, their in vivo characteristics and function 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 that the 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) with 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.

Proper maintenance of bone and BM medullary cavity is critical for blood cell development and diseases. We recently identified that a subset of Cxcl12+ stroma cells appear in tibial and femoral diaphysis, coinciding with the development of the medullary cavity. Surprisingly, upon bone injury, these cells readily respond and proliferate within the internal fracture callus and suppress bone forming cells with the recovery of BM cavity. Bone marrow also provides a specialized microenvironment (niche) for HSC function. To understand how stress signals control endogenous HSCs and their niche interaction, 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 identity of unique stroma progenitor cells with anti-osteogenic function and their regulation mechanism for BM medullary cavity maintenance and normal bone repair.

We are 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.

One Baylor Plaza, Margaret M. Alkek Biomedical Research Building (ABBR) R830, Houston, TX 77030

Primary Investigator: Dongsu Park, Dongsu.park@bcm.edu, (713)798-7950
Administative Assistant: Rhonda Patterson, rpatters@bcm.edu, (713)798-8824