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Laboratory for Growth Factors and Stem Cells
Our laboratory seeks to understand the molecular mechanisms that regulate tissue homeostasis with the long-term goal of developing novel approaches for regenerative therapies. We focus on the mammalian bone marrow microenvironment (niche), which maintains two distinct lineages of stem cells: hematopoietic stem cells (HSC) that give rise to blood; and skeletal stem cells (SSC) which form bone and fat. We are mostly interested in the extrinsic factors that regulate these stem cells, including growth factors, mechanical force, etc.
Growth Factors for Stem Cells
We employ a systematic genetic approach to identify new growth factor for stem cells. Specifically, we are interested in identifying secreted proteins with previously un-identified growth factor activities for adult skeletal stem/progenitor cells (LepR+ cells) in bone marrow. These new growth factors may regulate the self-renewal and/or differentiation of these cells thus promoting osteogenesis. One such factor we characterized was Clec11a/Osteolectin, which promotes the osteogenic differentiation of bone marrow stromal cells via integrin a11 (eLife 5:e18782; eLife 8:e42274). Identification of such growth factors and their prospective receptors could potentially provide novel druggable targets for the treatment of diseases such as osteoporosis, among others.
Heterogeneity of Stem Cells
Adult bone marrow LepR+ cells are heterogeneous, containing skeletal stem cells as well as osteogenic progenitors, adipogenic progenitors, fibroblasts, etc (Dev Cell 54:639). Identification of distinct sub-populations of LepR+ cells would further our understanding about the biology of bone marrow niche, providing potential new targets for blood and bone-related diseases. One such sub-population we identified was the Osteolectin-expressing peri-arteriolar osteogenic progenitors, which are required for both osteogenesis and lymphopoiesis (Nature 591:438-444).
Nerve Regulation of Blood Regeneration
The bone marrow contains peripheral nerve fibers that were suggested to be required for hematopoietic homeostasis and regeneration. We are investigating whether and how nerves regulate hematopoietic stem cell functions, by using genetic or pharmacological methods ablating nerves within the bone marrow niche.
Mechanobiology
We are interested in studying how mechanical force regulates tissue homeostasis from a molecular perspective. Our previous work demonstrated that mechanical force induced by exercise is required for the maintenance of osteogenic progenitors (Nature 503:131). Using a combination of cellular and molecular approaches, we are investigating the molecular mechanisms these cells employ to respond to mechanic force. We are interested to investigate the mechano-sensing mechanisms and signaling pathways used by platelets to adhere to injured site, leading to thrombus formation and hemostasis (Nature 503:131).