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The MPN Challenge grant is a process through which the Foundation makes grants for scientific work related to areas of unmet need in MPN research. The decision of which project to fund is made after a committee of MPN scientists review over 40 applicants, after which the Foundation board of directors (comprised mainly of patients and patient family members) votes to approve the projects. The grants reflect our interest in understanding the effect of suppressing the JAK2 mutation specifically, and not the wild type JAK2 which is needed for normal blood production; immunotherapy; gene editing, specifically CRISPR cas9; inflammation's role in the disease; and overall interest in a better understanding of what is happening in order to identify other targets for development of better therapies for MPN.
The projects funded for 2017-2019 are:
Angela G. Fleischman, MD, PhD, University of California, Irvine
Project Title: Inflammation as a Driver of Clonal Expansion in Myeloproliferative Neoplasm.
The goal of this project is to determine how JAK2 mutated
cells react to inflammation in comparison to normal blood producing cells. If inflammation plays a role to accelerate progression of MPN, this study would help define possible pathways to suppressing this inflammation.
James D. Griffin (M.D.), Martin Sattler (Ph.D.), Sara J. Buhrlage (Ph.D.), Ellen L. Weisberg (Ph.D.), Dana Farber Cancer Institute
Project Title: Inhibition of deubiquitinating enzymes as a novel targeted therapy for JAK2-dependent myeloid malignancies.
The goal of this project is to find a strategy to specifically target the JAK2-V617F mutation while leaving the wild type JAK2 mutation alone. The existing JAK2 inhibitors don't differentiate between the wild type JAK2 and the mutation which is correlated with diagnosis of MPN.
Vivian G. Oehler, MD, Marie Bleakley, MD, PhD, Fred Hutchinson Cancer Research Center
Project Title: Characterizing myeloproliferative neoplasm neoantigens and T cell responses for therapeutic applications.
The goal of this project will be to further our understanding of the potential of immunotherapy as an option for MPN.
Stephen Oh, M.D., PhD, Washington University in St. Louis
Project Title: Leveraging NFKB Pathway Dysregulation for Therapeutic Benefit in Myeloproliferative Neoplasms.
The goal of this project is to test the therapeutic potential of pevonedistat, which has been shown in a preliminary study in mice to reduce white blood cell counts and target the NFkB pathway which can become hyperactivated in MF and AML.
Rebekka K. Schneider, MD & Rafael Kramann, MD, Department of Hematology, Erasmus University Medical Center, Cancer Institute, Rotterdam, The Netherlands & Department of Nephrology, RWTH Aachen University, Aachen, Germany
Project Title: Functional and molecular dissection of the fibrotic transformation and clonal selection in myeloproliferative neoplasms.
Using CRISPRCas9 gene editing techniques, the goal of this project is to determine whether the S100A8/S100A9 molecule contributes to the growth of bone marrow fibrosis and loss of normal blood production. If confirmed, this presents a possible therapeutic target for drug development.
To see a complete list of research we have funded in our 15 years please click here. Our ability to fund these projects relates directly to the interest of people living with PV, ET and MF and their friends and families interest in supporting the Foundation. If you like the work we do please consider making a donation to support our research today.
Sincerely,
Michelle Woehrle
Executive Director, MPN Research Foundation
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