Cleveland Clinic cancer researchers receive $2.4 million grant from NIH NHLBI

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The National Institutes of Health National Heart, Lung and Blood Institute (NIH NHLBI) has awarded a $2.4 million grant over four years to Cleveland Clinic cancer researchers Jaroslaw Maciejewski, M.D., and Richard Padgett, Ph.D., to test the hypothesis that alterations in the pattern of splicing of target genes play a major role in the establishment or progression of myelodysplastic syndromes (MDS).

Through this work, the researchers aim to further clarify the role of spliceosomal factor mutations and deletions, commonly identified in myeloid malignancies, in the pathogenesis of these diseases through the identification of their effects on mRNA splicing in vivo and in vitro.

"Both clinical and specialized basic science expertise are required for the successful completion of the studies," said Dr. Maciejewski, who chairs the Department of Translational Hematology and Oncology Research in Cleveland Clinic's Taussig Cancer Institute and Lerner Research Institute. "In collaboration with Dr. Padgett's lab, we are eager to leverage this R01 grant to better understand spliceosomal defects in MDS."

Dr. Maciejewski's laboratory was among the first to report mutations in components of the spliceosomal machinery in myeloid malignancies, including MDS and acute myeloid leukemia (AML). Dr. Maciejewski's group has also extensively studied mutations in other pathways in MDS and AML. His clinical Bone Marrow Failure Program accrues around 120 new cases of MDS per year, which can be genotyped and provide a clinical substrate for this new research.

Dr. Padgett's laboratory in the Lerner Research Institute specializes in the investigation of spliceosomal function and has made key contributions to the understanding of spliceosomal biology. His and Dr. Maciejewski's laboratories have combined to publish studies on several spliceosomal proteins mutated in MDS and AML.

The NIH defines MDS as a group of cancers that occur when not enough mature, healthy blood cells are formed in the bone marrow. Approximately 10,000 Americans are diagnosed annually.

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