Positions

Assistant Professor
Molecular and Human Genetics
Baylor College of Medicine
Houston, TX, US
Assistant Professor
Pathology & Immunology
Baylor College of Medicine
Member
The Rolanette and Berdon Lawrence Bone Disease Program of Texas
Baylor College of Medicine
Member
Center for Skeletal Medicine and Biology
Baylor College of Medicine

Education

PhD from Baylor College of Medicine
Post-Doctoral Fellowship at Massachusetts General Hospital & Harvard Stem Cell Institute

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 define and characterize stem cell populations responsible for skeletal regeneration and repair in order to develop a method to improve the treatment of devastating bone and bone marrow diseases and cancer bone metastasis.

Identification of skeletal stem cell heterogeneity and regulatory mechanism: Adult skeletal stem cells (SSCs) are critical for life-long maintenance and regeneration of bone and bone marrow. However, the in vivo characteristics and function of SSCs are fundamental and 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 long-term repopulating, functionally distinct adult periosteal skeletal stem cells (P-SSCs) in vivo. These P-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 skeletal stem cells in the context of skeletal aging and to explore the clinical relevance of these cells in bone disorders and cancer bone metastasis.

In vivo mechanism of HSC niche cells: The maintenance and function of HSCs are finely controlled by a specialized microenvironment, HSC niche. 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 a novel animal model to selectively label endogenous HSCs 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.

Identification of muscle and tendon stem cells: My laboratory is also interested in the identity and function of mesenchymal populations in non-skeletal tissues such as muscle and tendon. However, their cellular origin and mechanisms that govern tissue regeneration and repair remain unanswered. A key question is whether mesenchymal stem/progenitor cells from different tissues behave differently in vitro and in vivo. My laboratory has the tools to answer these important questions using a variety of genetic, immunologic, and microscopic technologies with the goal of identifying molecules and mechanisms that regulate mesenchymal cells of different tissue origin. These studies will elucidate fundamental aspects of tissue regeneration and may lead to the development of new regenerative medicine strategies.

Selected Publications

Funding

Role of osteogenic stem/progenitors in bone regeneration and repair in vivo
- #K01 AR061434
NIH/NIAMS
Defining periosteal skeletal stem cells and novel migration mechanisms in bone regeneration and repair in vivo
- #R01 AR072018
Grant funding from NIH/NIAMS
Defining Periosteal Skeletal Stem Cell Heterogeneity and Age-associated Change
- #R21 AG064345
NIH/NIA