March 15, 2017

Cleveland Clinic Researcher Receives $5.5 Million Outstanding Investigator Award

Maciejewski honored for work in bone marrow failure syndromes

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Cleveland Clinic hematologist Jaroslaw Maciejewski, MD, PhD’s groundbreaking research efforts over two decades to decode the complex mechanisms of bone marrow failure syndromes have earned him the National Heart, Lung, and Blood Institute’s (NHLBI) Outstanding Investigator Award.

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The prestigious multi-year grant is meant to spur innovation by providing stable, long-term funding for a research program rather than an individual project. It is awarded to an investigator whose research record demonstrates the ability to make major scientific contributions, mentor others, advance the field and impact clinical care.

“The selection of Dr. Maciejewski for the Outstanding Investigator Award is proof that he is one of a handful of true leaders in the field of genetics, leukemias and bone marrow failure states,” says Brian J. Bolwell, MD, FACP, Chairman of Cleveland Clinic Cancer Center’s Taussig Cancer Institute. “He has the keenest scientific mind of anyone I have ever met. What sets him apart is his ability to marry scientific knowledge with clinical medicine, which very few researchers can do.”

The molecular basis of bone marrow failure syndromes

Bone marrow failure syndromes (BMFS) are inherited or acquired diseases characterized by failed blood production, failure of hematopoietic stem cells, and varying degrees of cellular proliferation. The spectrum of BMFS includes myelodysplastic syndromes, aplastic anemia and paroxysmal nocturnal hemoglobinuria.

Dr. Maciejewski, Chairman of Cleveland Clinic Cancer Center’s Department of Translational Hematology and Oncology Research, has focused on understanding the molecular basis of BMFS. Specifically, he has worked to characterize somatic and germline alterations of genes involved in hematopoietic cell proliferation, differentiation and regulation of metabolic processes, and to identify the consequences of those mutations.

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Dr. Maciejewski’s molecular profiling of various forms of BMFS using systematic next-generation sequencing has identified many new pathogenic genomic lesions and has enabled him to define new disease phenotypes and re-define existing ones. For example, in 2015 he and an international team identified acquired mutations normally found in leukemia in a large proportion of patients with aplastic anemia, which previously had been considered a nonmalignant condition. The mutations may indicate an early leukemic stage.

Developing genomic-based targeted therapies

Dr. Maciejewski’s intent is to use the improved molecular understanding of BMFS to develop genomic-based targeted therapies with the potential for cure, and biomarkers comparable to BRCA1/2 mutations in breast cancer that can identify at-risk BMFS patients for early intervention before disease progression.

“BMFS constitute a major, high-mortality medical problem and their incidence is likely to rise as life expectancy increases,” Dr. Maciejewski says. “The need to develop new therapies and diagnostic tools is great. Further understanding the pathogenesis of BMFS will bring important progress to many basic problems of hematopoiesis. I’m grateful to have the support to continue this work.”

Dr. Maciejewski is the author or coauthor of more than 320 scientific publications and participates in numerous international research collaborations. He previously was the recipient of four National Institutes of Health research project (R01) grants.

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