By Scott Edwards
Photography by Sam Ogden
The Edward P. Evans Foundation, which funds the most promising research in myelodysplastic syndromes (MDS), a type of blood cancer, has awarded grants totaling $2.325 million to five Dana-Farber researchers who are pursuing innovative MDS strategies.
As director of the Edward P. Evans Center for MDS at Dana-Farber, R. Coleman Lindsley, MD, PhD, is investigating the role of telomere dysfunction in MDS. Telomeres are caps at the end of each strand of DNA that protect chromosomes. Lindsley previously reported that inherited defects in the maintenance of telomeres are linked to MDS and that patients who have short telomeres have poor survival after bone marrow transplantation. This new funding will support improved clinical testing, influence treatment decisions, and aid in the design of new therapies for patients with MDS.
“I am grateful for the Evans Foundation’s support of this research. An improved understanding of how telomere damage influences development and treatment of MDS may further inform prognosis and drive the discovery of better treatment approaches,” said Lindsley.
With her grant, Zuzana Tothova, MD, PhD, is using research models of cohesin-mutant MDS to study the role of inflammation during disease development. Mutations in the cohesin protein complex occur in up to 20% of MDS. She will also investigate whether reactivating transposable elements, fragments of DNA inserted into our germline from ancient viral infection, drives MDS inflammatory changes, which could aid in developing new treatments.
Philipp Rauch, MD, is using barcoding technology to track blood cells to understand how the behavior of cells carrying a mutation for clonal hematopoiesis, an MDS precursor condition, differs from that of normal cells, which may help identify new therapeutic targets.
Previously, Rahul Vedula, MD, found that MDS cells carrying a specific mutation in the U2AF1 gene often have a mutation in the BCOR gene as well. He is studying the molecular mechanisms by which the two genes cooperate to drive MDS.
Hypomethylating agents are cornerstone treatments for MDS, but their anti-tumor mechanisms remain poorly understood. Rishi Puram, MD, PhD, is investigating epigenetic mechanisms that modulate cellular responses to hypomethylating agents, which may offer insight into new therapies that target DNA methylation in MDS.
“We are grateful for the talent, dedication, and commitment of our supported Dana-Farber investigators to finding solutions to the complex challenge of MDS, and we are proud to support their work,” said Michael Lewis, president of the Edward P. Evans Foundation.