
Researcher Profiles

Shu-Chi Yeh, Ph.D.
2025 Funding Recipient
Role of inflammatory landscapes shaped by resident marrow macrophages in MDS progression
Discovery Research Grant 2025
PROJECT SUMMARY
Myelodysplastic syndromes (MDS) are driven by blood stem cells carrying mutations that expand in the bone marrow and have high risks of leukemia transformation. The lack of second-line treatment for the elderly patients remains a major bottleneck to improve prognosis, suggesting a need for novel therapeutic strategies. A large body of evidence suggested that systemic inflammation nurtures mutant cells through mutation-specific mechanisms to defeat inflammatory insult and outcompete the healthy counterpart. Intriguingly, using live animal microscopy, we found that bone marrow is compartmentalized into mini cavities that undergo varied levels of bone resorption. The non-resorptive cavities were found to suppress MDS and leukemic clones while preserving potency of healthy stem cells under systemic inflammation. These results suggest the presence of a protective, anti-inflammatory niche, and the potential benefit of FDA-approved, anti-resorptive osteoporosis management in mitigating MDS progression. To determine the underlying mechanisms, using mouse models of MDS, we will isolate resident cells from mini cavities under microscopy image guidance for molecular and functional profiling. We will further validate the finding by analyzing marrow aspirates from MDS patients who received osteoporosis therapies. Completion of aims will identify targetable candidates to restrain mutant clones and better understand the roles of osteoporosis management in MDS progression.