Harry L. Grimes, Ph.D.
2017 Funding Recipient
Mechanisms of ineffective hematopoiesis underlying marrow failure syndromes
Discovery Research Grant 2017
Understanding the genetic and cellular cause of myelodysplastic-syndrome (MDS) is critical to derive and evaluate new therapies. Myelodysplastic-syndrome (MDS) is a disease of stem cells that form the blood. In MDS, abnormal stem cells accumulate but are unable to make enough functional blood cells. While we know that this process starts with mutations in specific genes, we do not know why such MDS-mutation-bearing cells have a competitive advantage over normal cells. Understanding this process is fundamental to figuring out new ways to treat patients, as well as determining whether current treatments are working. We have assembled a team of researchers, unique models and cutting edge technology to study the events occurring immediately after the mutation of MDS-associated genes. We expect to determine at a single cell level how MDS-genic mutations affect stem cell biology, and whether changes in the environment of the bone marrow help mutant stem cells generate disease.
David E. Muench, Kyle Ferchen, Chinavenmeni S. Velu, Kith Pradhan,2 Kashish Chetal, Xiaoting Chen, Matthew T. Weirauch, Clemencia Colmenares, Amit Verma, Nathan Salomonis, and H. Leighton Grimes, SKI controls MDS-associated chronic TGF-b signaling, aberrant splicing, and stem cell fitness, Blood 2018, DOI: 10.1182/blood-2018-06-860890.