PROJECT SUMMARY

Myelodysplastic syndromes (MDS) are a group of blood disorders where the bone marrow fails to produce enough healthy blood cells, leading to severe anemia, infection, and leukemia risk. While genetic mutations initiate the disease, chronic inflammation in the bone marrow acts as a “fuel” that drives disease progression. Current treatments often fail because they do not stop this underlying inflammation. Patients urgently need therapies that target this root cause to restore healthy blood production.My research has identified a protein called Galectin-1 (Gal-1) as a potential “master switch” for this harmful inflammation. We found Gal-1 is elevated in MDS patients and unlocks a specific receptor (TLR4) on immune cells to trigger a massive release of inflammatory signals. We hypothesize that blocking this pathway could “cool down” the marrow and allow healthy cells to recover.In this project, we will first confirm the molecular steps by which Gal-1 triggers inflammation in MDS. Simultaneously, we will use advanced single-cell technology to map the specific sugar patterns on bone marrow cells that allow Gal-1 binding. Next, we will genetically remove Gal-1 in mouse models to prove it is essential for disease progression. Finally, we will test if a drug inhibiting Gal-1—alone or with chemotherapy—can reverse bone marrow failure. If successful, this work will establish Gal-1 as a potential therapeutic target in MDS.