PREVIOUSLY FUNDED RESEARCH PROJECTS

• 2021 – 2023

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  • Sara Buhrlage, James Griffin, Jarrod Marto, and Ellen Weisberg (Dana-Farber Cancer Institute): “JOSD1 as a novel targeted therapy for JAK2V617F dependent myeloproliferative neoplasms.” Dr. Buhrlage’s project is being supported in part by The Leukemia & Lymphoma Society.
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  • Anandi Krishnan, Jason Gotlib, Holden Maecker, and James Zehnder (Stanford University): “Platelet, blood and plasma signatures of MPN subtype-specific risk.”
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  • Bridget Marcellino and Cansu Cimen Bozkus (Icahn School of Medicine at Mount Sinai): “Characterization of immune landscape and determinants of immune dysregulation in myeloproliferative neoplasms.”
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  • Josef T. Prchal (Huntsman Cancer Institute), Jihyun Song (University of Utah), Perumal Thiagarajan (Baylor College of Medicine), Tomas Ganz (University of California, Los Angeles) and Victor Gordeuk (University of Illinois): “Role of iron deficiency in thromboses of polycythemia vera.”
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  • Stephen Oh (Washington University, St. Louis): “Functional interrogation of an aberrant DUSP6-RSK1 signaling axis driving MPN pathogenesis.“

  2019 – 2021

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  • Matyas Ecsedi, MD, Ph.D., Fred Hutchinson Cancer Research Center “A JAK2 V617F -directed T cell receptor transgenic T cell immunotherapy for the treatment of myeloproliferative neoplasms” Partial funding in year one is being provided by the Fred Hutchinson’s Cancer Research Center’s Evergreen Fund
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  • Yelena Ginzburg, MD Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai “Dysregulated iron metabolism plays a pivotal role in polycythemia vera”
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  • Vikas Gupta, MD, Princess Margaret Cancer Center, University Health Network “Feasibility of a patient preferences-controlled study of allogeneic hematopoietic cell transplantation versus best available non-transplant therapies in patients with myelofibrosis (ALLO-BAT Study)”
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  • Catriona Jamieson, Ph.D., University of California, San Diego “Detection and Inhibition of Malignant RNA Processing Deregulation in Myelofibrosis”
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  • Alison Moliterno, MD, Johns Hopkins University School of Medicine “Targeting Thrombopoietin Signaling in the MPN”
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  • Jyoti Nangalia, MD, Ph.D., Wellcome Sanger Institute “Origins of MPN: Understanding the timing of acquisition of driver mutations and dynamics of clonal expansion”
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  • Vijay Sankaran, MD, Ph.D., Boston Children’s Hospital “Dissecting Germline Genetic Risk for Myeloproliferative”

• 2017 – 2019

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  • Angela G. Fleischman, MD, Ph.D., 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 the progression of MPN, this study would help define possible pathways to suppressing this inflammation. 
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  • James D. Griffin (MD), Martin Sattler (PhD), Sara J. Buhrlage (PhD), Ellen L. Weisberg (PhD), 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 the diagnosis of MPN.
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  • 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 applicationsThe goal of this project will be to further our understanding of the potential of immunotherapy as an option for MPN.
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  • Stephen Oh, MD, PhD, Washington University in St. Louis Project Title:  Leveraging NFKB Pathway Dysregulation for Therapeutic Benefit in Myeloproliferative NeoplasmsThe goal 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.
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  • 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

• 2015 – 2017

  • George Church, PhD Click here for project details Harvard Medical School “Establishment of isogenic human induced pluripotent stem cell (hiPSC) lines containing CRISPR engineered MPN mutations”
  • Camelia Iancu-Rubin, PhD and Nina Bhardwaj, MD, PhD Icahn School of Medicine at Mount Sinai “Defining the immunomodulatory properties of mutated calreticulin in MPN”
  • Zhijian Qian, PhD and Wen-Shu Wu, PhD Click here for project details University of Illinois at Chicago “Correction of JAK2 mutation in myeloproliferative neoplasms by gene editing”
  • Brady Stein, MD Northwestern Feinberg School of Medicine “Anti-PDL1 therapy for patients with Myelofibrosis”
  • Zhaohui Ye, PhD Click here for project details Johns Hopkins “Precise Genome Editing for Targeting Malignant Clones in MPNs”

  • 2014 – 2015

    • Steven Hubbard, PhD New York University “Testing for small molecules for selective JAK2 inhibition”
    • Nadia Carlesso & H. Schott Boswell Indiana University School of Medicine “Impact of the inflamed bone marrow niche on the progression of Myeloproliferative Neoplasia and marrow fibrosis”
    • Michael Deininger Huntsman Cancer Institute, University of Utah School of Medicine “Engineering CAR T Cells That Target Mutant CALR as a Novel Therapeutic for Myeloproliferative Neoplasms”
    • Angela Fleischman & Richard Van Etten University of California, Irvine “A key role for lymphoid cells in the pathology of myeloproliferative neoplasm”
    • Lei Ding Columbia University Medical Center “Hematopoietic stem cell niche in myelofibrosis”
    • Robert Kralovics CEMM, Austria “Immunologic Targeting of Calreticulin Gene Mutations in MPN”
    • Ann Mullally The Brigham and Women’s Hospital “Determination of the role of altered epigenetic regulation of megakaryocytes in the pathogenesis of myelofibrosis”
    • Katya Ravid Boston University School of Medicine “Nanoplatforms for Imaging Bone Marrow Fibrosis”
    • Gary W. Reuther Moffitt Cancer Center “Using Pharmacological Synthetic Lethality to Treat MPNs”
    • Jean-Luc Villeval, Sandra Pellegrini, Stefan Constantinescu INSERM/Institut Gustave Roussy/University Paris XI, France; Institut Pasteur Paris, France; de Duve Institute, Université catholique de Louvain, Brussels, Belgium, and Ludwig Cancer Research Institute, Brussels, Belgium “Project Title: Mechanisms of Sensibility and Resistance of MPN Hematopoietic Stem Cells to IFNα Therapy”
    • Leonard Zon Boston Children’s Hospital “Identifying factors that promote clonal dominance in zebrafish hematopoiesis for the treatment of myeloproliferative neoplasms”

• 2013 – 2014

  • John Varga and Jonathan Licht Northwestern University “Adipocytes – the cell of origin of fibrosis in myeloproliferative neoplasm?”
  • Golam Mohi State University of New York “Molecular mechanism of myelofibrosis induced by JAK2V617F”
  • Emmanuelle Passegué The University of California at San Francisco “Targeting the remodeling of the osteoblastic bone marrow niche by MPN myeloid cells to prevent myelofibrosis”
  • Xiaoli Wang Mt. Sinai School of Medicine “The role of thrombopoietin and its receptor in myelofibrosis”

• 2011 – 2013

  • Ann Mullaly & Benjamin L. Ebert Brigham and Women’s Hospital “Determination of the cytokines that are necessary and sufficient to include fibrotic transformation in JAK2V617F-mediated MPN”
  • Amit Verma and Zhizhuang Joe Zhao Albert Einstein College of Medicine & University of Health Sciences Center “Efficacy of a clinically relevant TGF-Beta receptor kinase inhibitor in myelofibrosis”
  • Pearlie Epling-Burnette and Adam Mailloux H. Lee Moffitt Cancer Center “Blockade in mesenchymal stromal self-renewal as a novel mediator of the profibrotic marrow phenotype”
  • C. Arnold Spek Center for Experimental and Molecular Medicine, Austria “Bone marrow fibrosis: proof of principle for a potential therapeutic role of protease-activated receptor inhibitors”
  • Established Investigators:
  • Ruben Mesa, MD Mayo Clinic, Scottsdale “Validation of the use of the Myeloproliferative Neoplasm Symptom Assessment Form Diary to Assess Symptomatic Pains in Patients with Polycythemia Vera and Post Polycythemia Vera”
  • Robert I. Handin, MD Brigham and Women’s Hospital, Harvard Medical School “HDAC Inhibitors and Red Cell Proliferation in Zebrafish Embryos Expressing Human JAK2V617F”
  • Shaoguang Li, MD PhD University of Massachusetts Medical School “Identification of Alox5 as a Potential Target Gene for the Treatment of Polycythemia Vera”
  • Robert Kralovics, PhD Austrian Academy of Sciences, Vienna “Deciphering the Genetic Complexity of Myeloproliferative Disorders” Research results: Discovery of CALR genetic mutation for MPNs (December 2013)
  • Benjamin Ebert, MD Ph.D., and Ross Levine, MD Harvard Medical School and Memorial Sloan Kettering, respectively “Whole Genome Sequencing to Identify Germline and Somatic Disease Alleles Which Contribute to MPD Pathogenesis”
  • New Investigators:
  • Toshiaki Kawakami, MD PhD La Jolla Institute for Allergy and Immunology “SPS Complex in MPD”
  • Wei Tong, PhD Children’s Hospital of Pennsylvania “K63 Ubiquitination in JAK2 Signaling and Myeloproliferative Neoplasms”
  • Saghi Ghaffari, MD PhDMt. Sinai School of Medicine “Understanding Molecular Mechanisms of Regulation of Myeloproliferative Disorders in Mouse and Human”

• 2009 – 2010

  • Gary Gilliland, MD, PhD Harvard Medical School “Genetics and Therapy of Myeloproliferative Disorders”
  • Ronald Hoffman, MD Mt. Sinai School of Medicine “Use of Stem Cells Derived from the Philadelphia Chromosome Negative Myeloproliferative Disorders as a Chemotherapeutic Target”
  • Josef Prchal, MD University of Utah Define somatic mutations that precede JAK2 mutation in PV patients & monitor their changes in response to Pegasys”
  • Ayalew Tefferi, MD Mayo Clinic “Continued Development of Clinical Database-Linked Cell and Serum Bank of Patients with Myeloproliferative Disorders”
  • New Investigator:
  • Benjamin Braun, MD, PhD University of California, San Francisco “Oncogenic Ras in Leukemia Stem Cells”
  • Francois Delhommeau, Ph.D., PharmD Saint-Antoine Hospital, Paris “Characterization and Function of a New Tumor Suppressor Gene in Myeloproliferative Disorders”
  • Robert Kralovics, PhD Austrian Academy of Sciences, Vienna “Genomic approaches for disease gene identification in myeloproliferative neoplasms”
  • Dorothy Sipkins, MD, PhD University of Chicago “In Vivo Imaging of PV and CIMF CD34+ Progenitor Cell Interactions with Bone Marrow Microenvironment”

• 2006 – 2008

  • Gary Gilliland, Ph.D., MD (MPD Research Alliance) Harvard Medical School
  • Ayalew Tefferi, MD (MPD Research Alliance) Mayo Clinic, Rochester
  • Ronald Hoffman, Ph.D. (MPD Research Alliance) Mt. Sinai School of Medicine (2007-Present) University of Illinois, Chicago (2006-2007)
  • Gail Roboz, MD Weill Cornell Medical College “Arsenic trioxide (ATO) combined with cytosine arabinoside (ara-c) for the treatment of advanced myelofibrosis and myelofibrosis transformed to acute myeloid leukemia”

• 2000 – 2005

  • 2005

  • Xiaomei Ma, PhD Yale University School of Medicine “Epidemiology of Chronic Myeloproliferative Disorders Grant”

  • 2004

  • Alison Moliterno, MD Johns Hopkins “Proteomic Approach to the Diagnosis of Chronic MPD’s.
  • Mingjiang Xu, MD, Ph.D. The University of Illinois, at Chicago “Exploration of a unique phosphatase as a potential therapeutic target for the treatment of PV”
  • Ron Hoffman, MD The University of Illinois at Chicago “Continuation of 2003 grant. “
  • Jose Lopez, MD Baylor College of Medicine “Macrophage-derived Prothrombotic Microparticles and Thrombosis in Myeloproliferative Disorders”

  • 2003

  • Xiao-Feng Yang, MD, PhD Baylor College of Medicine “Novel Antigen targets for Immunotherapy in the Myeloproliferative Diseases”
  • Ruben Mesa, MD Mayo Clinic, Rochester, NY “Novel therapies for Myelofibrosis with Myeloid Metaplasia”
  • Richard D’Andrea, MD Child Health Research Institute, Australia “Identification of Growth Factor Receptor Mutations in Polycythemia Vera”
  • Ron Hoffman, MD The University of Illinois at Chicago “Organizational grant for International MPD Research Consortium in the application for $25 million grant from NCI”
  • Vahid Afshar-Kharghan, MD Baylor College of Medicine “Continuation of 2002 Grant”

  • 2002

  • Vahid Afshar-Kharghan MD Baylor College of Medicine “Genetic factors that influence platelet function in PV and ET, and their effect on the frequency of thrombotic complications.”
  • Dr. Josef Prchal Baylor College of Medicine “Continuation of 2001 Grant”
  • Dr. Josef Prchal Baylor College of Medicine “Continuation of 2000 Grant”

  • 2001

  • Dr. Josef Prchal Baylor College of Medicine “Locate and identify the gene or genes whose defects are responsible for ET.”
  • Dr. Josef Prchal Baylor College of Medicine “Continuation of 2000 Grant”

  • 2000

  • Dr. Josef Prchal Baylor College of Medicine “Locate and identify the gene or genes that lead to the development of the Polycythemia Vera phenotype.