2022 Thrive Initiative

2022 Thrive Initiative

As always, we are grateful to the MPN community and our funders who make these programs possible to advance the collective pursuit of new therapies and better outcomes for patients. The Leukemia & Lymphoma Society, in its continued support of MPNRF, is contributing funds over the three-year effort to enable funding of more projects and expand our reach into the research community. Special thanks to Shelley Spevakow of the SSASSY Foundation for her contributions towards the PV projects, the generous bequest of Susan Ann Protter for providing an anchor for our research, and the ongoing contributions of our generous benefactors.

2022 Thrive Initiative AwardEES & Projects

MPN Research Foundation (MPNRF) announced the 2022 Thrive Initiative earlier this year, a research funding program focused on supporting and expanding MPN research that will catalyze significant discoveries towards a better understanding of and cures for patients challenged with the myeloproliferative neoplasms (MPNs), myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET).  Through this initiative we hope to address research-funding gaps, some of which are likely due to the impact of the pandemic on the research community. This multifaceted funding program is intended to:
  1. Advance existing MPN research projects the applicant is engaged in currently.
  2. Foster the growth and development of early-career MPN researchers.
  3. Attract established researchers that are new to the MPN field.
  4. Encourage collaborative translational projects with near-term clinical impact.
In total, 45 applications totaling approximately $10M in requested funding were received. A peer review panel consisting of 20 engaged expert scientists and clinicians from around the world evaluated these applications. The MPNRF Science Steering Committee (SSC) discussed the peer review results and recommended funding the following 11 projects totaling $1.784M over 2 years with the second year contingent on satisfactory research progress. The SSC recommendation includes funding for 4 Follow On Support projects, 1 New Investigator with New Ideas project, and 6 Junior Investigator projects. We are excited about the results of the process and believe that the following 11 projects will achieve the multifaceted goals of the Thrive Initiative.  

Four projects awarded, up to $100,000 each over one year.
Objective: Preserve and advance existing promising MPN research that would otherwise languish.

Awardees

John D. Crispino, PhD, MBA, St. Jude Children’s Research Hospital
Project title: “Aberrant Megakaryopoiesis in the MPNs”

  • • A major goal of the lab is to better understand the factors that drive MPN MKs toward ET versus MF and develop strategies to prevent or slow disease progression 
  • • The ultimate goal is to use this latest information to develop therapeutic agents/strategies to prevent or inhibit aberrant MKs development and progression to MF 
  •  

Michal Bar-Natan, Icahn School of Medicine at Mt. Sinai 
Project title: “Harnessing the immune system to target Calreticulin mutant myeloproliferative neoplasms”

  • • This research team has developed a vaccine that targets mutated CALR with the goal of enhancing the immune response in MPN patients 
  • • This project represents the initial testing of this vaccine in a clinical trial in MPN patients
     

Nicole Kucine, MD, MS, Weill Cornell Medicine
Project title: “Analysis of Mutational Spectrum in Pediatric Myeloproliferative Neoplasms”

  • • Children and young adults are diagnosed with MPNs and the genetic factors contributing to disease onset and progression have not been well studied 
  • • Dr. Kucine has developed a database of children and young adults with MPNs and will use this funding to continue to follow and expand this patient population to compare and contrast the role of genetics in this patient population versus that already known in adults

 
Joe Scandura, MD, PhD, Weill Cornell Medicine
Project title: “Tracking MPN Fitness to speed development of disease modifying agents for MPNs”

  • • This project will develop a new surrogate clinical measure called “MPN Fitness” that can potentially predict major events like thrombosis and disease progression and response to therapy 
  • • The goal of this project is to further simplify the MPN fitness procedure making it more user friendly and robust for future clinical trials and further validation  

 

Six projects awarded, up to $200,000 each over two years
Objective: Provide an opportunity for junior investigators to compete exclusively with their peers for an MPNRF grant and enhance their capacity for future funding in the MPN field.

Awardees

Idoroenyi Amanam, MD, MS, City of Hope National Medical Center
Project title: “Investigation of IL-1RAP in Myeloproliferative Neoplasms: Potential novel anti-leukemic therapy” 

  • • Immunotherapies such as Bispecific antibodies (BsAb) such as blimatomomab that involve T cells are shown to be effective in cancers such as leukemia 
  • • Amanam group proposes to reduce the toxicity to normal stem cells by using BsAb to target the cancer stem cells expressing proteins called IL1RAP and CD3 that is present on MPN stem cells


Najla Arshad, PhD,
 Yale University School of Medicine
Project title: “Development of nanobody-based targeted therapy for myeloproliferative neoplasms” 

  • • Around 35% of MPNs are driven by a mutant protein called calreticulin (CALR), which is responsible for protein folding and antigen presentation by major histocompatibility class I (MHC-I) complexes 
  • • This group plans to target the pathogenic CALR-FS-TPO-R [frameshift mutations in CALR (CALR-FS) and thrombopoietin growth factor receptor (TPO-R)] interaction and MPN-associated peptide-MHC-I complexes, and then other unidentified cell surface alterations


Joan Beckman
, MD, PhD, University of Minnesota, Twin Cities
Project title: “Role of Gas6-Axl-MERTK in Myeloproliferative Neoplasm Thrombosis” 

  • • This project will explore a potential signaling pathway driving thrombosis in MPN patients 
  • • This research has near term implications as there is the potential for rapid translation of results into a clinical trial with an established late-stage investigational agent called bemcentinib


Sahand Hormoz
, PhD, Dana-Farber Cancer Institute
Project title: “A new mouse model of the early phase of myeloproliferative neoplasms for probing disease heterogeneity” 

  • • This project seeks to develop a mouse model to study the factors that drive different disease outcomes in people who have MPN driver mutation, JAK2V617F, that can lead to PV and other MPNs  
  • • This model system, if successful, will enable the testing of therapeutic strategies can potentially delay or prevent the onset of disease

Shannon Elf, PhD, University of Chicago
Project title: “Dissecting the pathophysiological role of GLUT1 in driving type 1 CALR-mutated myeloproliferative neoplasms” 

  • • This group proposes to understand how Type-1 CALR mutation leads to metabolic changes, including up-regulated glucose uptake in mutant cells, and how targeting it can specifically kill type 1 CALR-mutated MPN cells while sparing normal ones. 
  • • They are testing this treatment modality in triple negative breast cancer to determine whether this is a viable treatment option for MPN patients 


Shinobu Matsuura,
DVM, PhD, Boston University School of Medicine
Project title: “Targeting the JAK2V617F Hematopoietic Stem Cell Through Integrins-Based Combination” 

  • • This group has previously shown that an anti-beta 1 integrin (activates JAK2) inhibitory antibody given to mice with MPN significantly reduced the mutated stem cells numbers with negligible effects in normal mice. 
  • • The goal of this project is to determine if this antibody therapeutic approach can lead to complete MPN stem cell exhaustion (with potentially curative implications) and be a viable and safe therapy. 

One project awarded, up to $200,000 over two years. 
Objective: To provide a competitive funding environment for researchers new to the MPN field bringing novel ideas into MPN research.

Ioannis Aifantis, PhD New York University Grossman School of Medicine
Project title: “Dissecting and targeting transcriptional and epigenetic regulation in advanced myelofibrosis (MF)” 

  • • Their previous studies show that blood formation in the spleen is biased toward the myeloid lineages therefore lacking normal blood cell formation 
  • • The project focused on understanding the controlling factors for this bias and testing therapeutic approaches to MF

Questions?

Please email any questions to grants@mpnrf.org

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