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INFORMATION FOR

Stephanie Halene, MD, Dr Med

Arthur H and Isabel Bunker Associate Professor of Medicine (Hematology) and Associate Professor of Pathology; Chief, Section of Hematology; Director, DeLuca Center for Innovation in Hematology Research, Yale Cancer Center; Assistant Medical Director CRSL, Yale Cancer Center

Research Summary

Dr. Halene's laboratory studies hematopoiesis and myelopoiesis and in particular how abnormalities of the hematopoietic stem and progenitor cells lead to diseases with abnormal numbers and function of blood cells such as in Myelodysplastic Syndromes and Leukemia. The laboratory uses primary patient cells and murine models to study mechanisms of disease leading to myelodysplasia and acute myeloid leukemia with the ultimate goal to contribute to the development of novel treatments.

Specialized Terms: Hematopoiesis; Leukemia; Myelodysplasia; Myelodysplastic syndrome; Stem cells; Humanized mice; Xenotransplantation; PDX models; RNA biology; RNA splicing; RNA modifications

Extensive Research Description

Below find a description of our ongoing research projects in the Halene Lab:

Splicing Factor Mutations in Myeloid Malignancies: We seek to understand the role of mutations in splicing factors (SFs), present in nearly 50% of patient with MDS and a subset of patients with AMLs. Mutations in SFs are not only recurrent in nature, affecting specific amino acid positions, but also mutually exclusive; patients carry mutations in only one splicing factor. This suggests a common mechanism in the pathogenesis of MDS. We employ structural, molecular biology, and multi-omic approaches, and in vivo xenotransplantation to determine disease mechanism and develop novel therapeutics.

RNA modifications: We are interested how RNA modifications determine hematopoietic stem and progenitor cell function. We discovered that loss of METTL3 and the m6A RNA modification results in the aberrant formation of double stranded RNA and activation of a deleterious innate immune response. We treasure numerous collaborations within Yale's RNA Center to apply cutting edge technologies and deep understanding of RNA biology to hematologic disorders.

MDS/AML Co-clinical Models: MDS and AML are inherently difficult to study. They are heterogeneous diseases; only rare human cell lines have been successfully derived from patients’ MDS and few from patients with AML; hematopoietic and leukemic stem cells (HSC/LSC) do not grow in culture and MDS stem cells fail to efficiently engraft even in the best currently available mouse models. In collaboration with the Flavell laboratory we have developed the first highly efficient xenotransplantation model for MDS/AML in the humanized MISTRG mice amenable to drug treatments. We continue to improve upon this model to extend our studies to diseases of red cell production and the human immune system. We are collaborating with the Fan lab in the Yale Biomedical Engineering Department and the Grimes lab at Cincinnati Children's Hospital to generate multi-omic maps of MDS and AML in their microenvironments.

Hematology Tissue Bank: The Hematology Tissue Bank has been established to give researchers access to critical patient samples for the study of hematologic diseases. Should you wish to obtain samples for your research contact Dr. Halene via phone (203 785-7002) or e-mail (stephanie.halene@yale.edu).

Mouse Modeling Core (AMC) – Yale Cooperative Center of Excellence in Hematology (YCCEH): The Mouse Modeling Core, directed by Richard Flavell and Stephanie Halene, is part of the YCCEH with the goal to provide researchers with access to the latest technologies for hematologic studies in animal models. The AMC offers expertise, technical assistance, and mice for human-into-mouse xenotransplantation studies. It offers training and technical assistance in the study of hematopoiesis and benign hematologic questions in mice.

Coauthors

Research Interests

Hematopoiesis; Hematopoietic Stem Cells; Leukemia; Myelodysplastic Syndromes; RNA Splicing; Alternative Splicing; Xenograft Model Antitumor Assays

Research Images

Selected Publications

  • Deconvolution of in vivo protein-RNA contacts using fractionated eCLIP-seqBiancon G, Busarello E, Joshi P, Lesch B, Halene S, Tebaldi T. Deconvolution of in vivo protein-RNA contacts using fractionated eCLIP-seq STAR Protocols 2022, 3: 101823. PMCID: PMC9676202, DOI: 10.1016/j.xpro.2022.101823.
  • A Multi-Center Phase Ib Trial of the Histone Deactylase Inhibitor (HDACi) Entinostat in Combination with Anti-PD1 Antibody Pembrolizumab in Patients with Refractory/Relapsed Myelodysplastic Syndromes (RR-MDS) or Oligoblastic Acute Myeloid Leukemia (RR-AML) after Hypomethylating Agent (HMA) FailureBewersdorf J, Shallis R, Sharon E, Caldwell A, Wei W, Yacoub A, Madanat Y, Zeidner J, Altman J, Odenike O, Yerrabothala S, Kovacsovics T, Podoltsev N, Halene S, Little R, Piekarz R, Gore S, Kim T, Zeidan A. A Multi-Center Phase Ib Trial of the Histone Deactylase Inhibitor (HDACi) Entinostat in Combination with Anti-PD1 Antibody Pembrolizumab in Patients with Refractory/Relapsed Myelodysplastic Syndromes (RR-MDS) or Oligoblastic Acute Myeloid Leukemia (RR-AML) after Hypomethylating Agent (HMA) Failure Blood 2022, 140: 9084-9086. DOI: 10.1182/blood-2022-158626.
  • Enhanced Global Disease Assessment with Advanced Imaging and Targeted Myeloma Lesion Biopsy Highlights Spatial Heterogeneity and Detects Residual Disease in Multiple MyelomaBrowning S, Liu Y, Parker T, Bar N, Anderson T, Dhodapkar M, Seropian S, Halene S, Xu M, Syam R, Gorshein E, DiAdamo A, Talsania A, Kidwai W, Witt D, Chang V, Montanari F, Lischuk A, Wei W, Haims A, Neparidze N. Enhanced Global Disease Assessment with Advanced Imaging and Targeted Myeloma Lesion Biopsy Highlights Spatial Heterogeneity and Detects Residual Disease in Multiple Myeloma Blood 2022, 140: 7308-7310. DOI: 10.1182/blood-2022-166325.
  • Genomic Sequencing of Paired Bone Marrow and Focal Lesion Biopsies of Newly Diagnosed Multiple Myeloma Patients before and after Induction TherapyLiu Y, Browning S, VanOudenhove J, Biancon G, Bar N, Parker T, Anderson T, Dhodapkar M, Seropian S, Halene S, Xu M, Gorshein E, Talsania A, Kidwai W, Witt D, Chang V, Montanari F, Lischuk A, Haims A, Wei W, Neparidze N. Genomic Sequencing of Paired Bone Marrow and Focal Lesion Biopsies of Newly Diagnosed Multiple Myeloma Patients before and after Induction Therapy Blood 2022, 140: 7086-7087. DOI: 10.1182/blood-2022-168109.
  • U2AF1 Splicing Factor Mutations Affect RNA Subcellular Compartmentalization in Myeloid MalignanciesBiancon G, Busarello E, Lessard M, Courvan E, Escayola D, VanOudenhove J, Lee V, Krick M, Bewersdorf J, Neugebauer K, Tebaldi T, Halene S. U2AF1 Splicing Factor Mutations Affect RNA Subcellular Compartmentalization in Myeloid Malignancies Blood 2022, 140: 1271-1272. DOI: 10.1182/blood-2022-170043.
  • Molecular, Epigenetic, and Immune Landscape of TP53- mutated (TP53-M) Acute Myeloid Leukemia (AML) and Higher Risk Myelodysplastic Syndromes (HR-MDS)Bewersdorf J, Hasle V, Shallis R, Thompson E, Lopes de Menezes D, Rose S, Boss I, Halene S, Haferlach T, Fox B, Zeidan A. Molecular, Epigenetic, and Immune Landscape of TP53- mutated (TP53-M) Acute Myeloid Leukemia (AML) and Higher Risk Myelodysplastic Syndromes (HR-MDS) Blood 2022, 140: 6247-6249. DOI: 10.1182/blood-2022-156460.
  • Impact of Allelic State on Overall Survival in TP53- mutant Acute Myeloid Leukemia (AML) and Higher Risk Myelodysplastic Syndromes (HR-MDS)Bewersdorf J, Hasle V, Shallis R, Thompson E, Lopes de Menezes D, Rose S, Boss I, Halene S, Haferlach T, Fox B, Zeidan A. Impact of Allelic State on Overall Survival in TP53- mutant Acute Myeloid Leukemia (AML) and Higher Risk Myelodysplastic Syndromes (HR-MDS) Blood 2022, 140: 8910-8911. DOI: 10.1182/blood-2022-158592.
  • Harmonizing the Annotation of Hematopoietic Populations in Single-Cell Atlases with the Cell Marker AccordionBusarello E, Ibnat Z, Biancon G, VanOudenhove J, Lauria F, Viero G, Halene S, Tebaldi T. Harmonizing the Annotation of Hematopoietic Populations in Single-Cell Atlases with the Cell Marker Accordion Blood 2022, 140: 4968-4969. DOI: 10.1182/blood-2022-162180.
  • Proteomic Profiles of Cytokine Release Syndromes Following Lisocabtagene Maraleucel and Idecabtagene VicleucelMirza A, Pine A, Rasheed Y, Hamouche R, Leveille E, Goshua G, Gu S, Liu Y, VanOudenhove J, Bar N, Neparidze N, Foss F, Gowda L, Isufi I, Halene S, Lee A, Seropian S. Proteomic Profiles of Cytokine Release Syndromes Following Lisocabtagene Maraleucel and Idecabtagene Vicleucel Blood 2022, 140: 10410-10412. DOI: 10.1182/blood-2022-168374.
  • Repressive β-Catenin-Ikaros Complexes Are Essential to Prevent Clonal Evolution of Human LymphopoiesisCosgun K, Liu W, Robinson M, Fonseca Arce D, VanOudenhove J, Bigogno A, Flavell R, Halene S, Müschen M. Repressive β-Catenin-Ikaros Complexes Are Essential to Prevent Clonal Evolution of Human Lymphopoiesis Blood 2022, 140: 8744-8745. DOI: 10.1182/blood-2022-170409.
  • MYOCARDIAL IMPACT OF CLONAL HEMATOPOIESIS OF INDETERMINATE POTENTIAL (CHIP) SECRETOMES IN CARDIO-ONCOLOGY PATIENTSKwan J, Vanoudenhove J, Vanoudenhove J, Halder S, Halder S, Biancon G, Jain K, Jain K, Chakraborty R, Lustberg M, Lustberg M, Pusztai L, Campbell S, Campbell S, Zhao H, Halene S, Hwa J. MYOCARDIAL IMPACT OF CLONAL HEMATOPOIESIS OF INDETERMINATE POTENTIAL (CHIP) SECRETOMES IN CARDIO-ONCOLOGY PATIENTS Journal Of The American College Of Cardiology 2022, 79: 1912. DOI: 10.1016/s0735-1097(22)02903-5.
  • ALKBH5 Modulates Hematopoietic Stem and Progenitor Cell Energy Metabolism through m 6a Modification-Mediated RNA StabilityGao Y, Zimmer J, Vasic R, Liu C, Gbyli R, Zheng S, Patel A, LIU W, Nelakanti R, Song Y, Biancon G, Xiao A, Slavoff S, Simon M, Flavell R, Tebaldi T, Li H, Halene S. ALKBH5 Modulates Hematopoietic Stem and Progenitor Cell Energy Metabolism through m 6a Modification-Mediated RNA Stability Blood 2021, 138: 298-298. DOI: 10.1182/blood-2021-146049.
  • U2AF1 Mutations Enhance Stress Granule Response in Myeloid MalignanciesBiancon G, Joshi P, Zimmer J, Hunck T, Gao Y, Lessard M, Courchaine E, Barentine A, Machyna M, Botti V, Qin A, Gbyli R, Patel A, Song Y, Kiefer L, Viero G, Neuenkirchen N, Lin H, Bewersdorf J, Simon M, Neugebauer K, Tebaldi T, Halene S. U2AF1 Mutations Enhance Stress Granule Response in Myeloid Malignancies Blood 2021, 138: 321-321. DOI: 10.1182/blood-2021-149618.
  • Compromised Host Stem Cell Competitiveness Affords Fanconi Stem Cell Engraftment in C-Kit Mutant Humanized MiceLIU W, Song Y, Gbyli R, Sefik E, Biancon G, Gao Y, Philbrick W, Patel A, Tebaldi T, Nalepa G, Kupfer G, Flavell R, Halene S. Compromised Host Stem Cell Competitiveness Affords Fanconi Stem Cell Engraftment in C-Kit Mutant Humanized Mice Blood 2021, 138: 1119-1119. DOI: 10.1182/blood-2021-153777.
  • CARDIOVASCULAR AND MORTALITY OUTCOMES IN ONCOLOGY PATIENTS HOSPITALIZED WITH COVID-19Kwan J, Lee S, Tao W, Wei W, Simonov M, Halene S, Hwa J, Baldassarre L. CARDIOVASCULAR AND MORTALITY OUTCOMES IN ONCOLOGY PATIENTS HOSPITALIZED WITH COVID-19 Journal Of The American College Of Cardiology 2021, 77: 3294. PMCID: PMC8091382, DOI: 10.1016/s0735-1097(21)04648-9.
  • CARDIOVASCULAR AND MORTALITY OUTCOMES OF HOSPITALIZED COVID-19 PATIENTS STRATIFIED BY RACE AND ETHNICITYKwan J, Lee S, Tao W, Wei W, Simonov M, Halene S, Hwa J, Spatz E. CARDIOVASCULAR AND MORTALITY OUTCOMES OF HOSPITALIZED COVID-19 PATIENTS STRATIFIED BY RACE AND ETHNICITY Journal Of The American College Of Cardiology 2021, 77: 3050. PMCID: PMC8091439, DOI: 10.1016/s0735-1097(21)04405-3.
  • Advanced Imaging and Targeted Myeloma Lesion Biopsies to Enhance Global Response Assessment and Evaluate Spatial Heterogeneity in Multiple MyelomaBrowning S, Parker T, Bar N, Anderson T, Dhodapkar M, Seropian S, Lee A, Prebet T, Halene S, Xu M, Gorshein E, Talsania A, Kidwai W, Witt D, Chang V, Lischuk A, Wei W, Haims A, Neparidze N. Advanced Imaging and Targeted Myeloma Lesion Biopsies to Enhance Global Response Assessment and Evaluate Spatial Heterogeneity in Multiple Myeloma Blood 2020, 136: 20-22. DOI: 10.1182/blood-2020-136478.
  • Reconstruction of Sickle Cell Disease with Circulating Sickling Red Blood Cells in Novel Humanized Cytokines and Liver Mistrg MiceSong Y, Gbyli R, Shan L, Liu W, Gao Y, Patel A, Fu X, Wang X, Xu M, Qin A, Bruscia E, Tebaldi T, Biancon G, Mamillapalli P, Urbonas D, Gonzales D, Krause D, Alderman J, Flavell R, Halene S. Reconstruction of Sickle Cell Disease with Circulating Sickling Red Blood Cells in Novel Humanized Cytokines and Liver Mistrg Mice Blood 2020, 136: 29-30. DOI: 10.1182/blood-2020-141603.
  • High-Resolution Binding Atlas of U2AF1 Mutants Uncovers New Complexity in Splicing Alterations and Kinetics in Myeloid MalignanciesBiancon G, Joshi P, Hunck T, Zimmer J, Gao Y, Machyna M, Botti V, Qin A, Viero G, Neuenkirchen N, Taylor A, Gbyli R, Patel A, Ardasheva A, Fu X, Lin H, Simon M, Neugebauer K, Tebaldi T, Halene S. High-Resolution Binding Atlas of U2AF1 Mutants Uncovers New Complexity in Splicing Alterations and Kinetics in Myeloid Malignancies Blood 2020, 136: 3-4. DOI: 10.1182/blood-2020-142854.
  • Clinical Outcomes of Patients (pts) with TP53-Mutated Acute Myeloid Leukemia (AML) or Myelodysplastic Syndromes (MDS): A Single Center ExperienceBewersdorf J, Shallis R, Gowda L, Hager K, Podoltsev N, Gore S, Prebet T, Halene S, Isufi I, Foss F, Huntington S, Kim T, Pillai M, Parker T, Neparidze N, Bar N, Seropian S, Siddon A, Zeidan A. Clinical Outcomes of Patients (pts) with TP53-Mutated Acute Myeloid Leukemia (AML) or Myelodysplastic Syndromes (MDS): A Single Center Experience Blood 2019, 134: 5173-5173. DOI: 10.1182/blood-2019-127162.
  • Isolated Trisomy 11 in Patients with Myeloid Malignancies - Is the Prognosis Not As Grim As Previously Thought?Bewersdorf J, Shallis R, Diadamo A, Gowda L, Podoltsev N, Gore S, Prebet T, Halene S, Isufi I, Foss F, Huntington S, Kim T, Pillai M, Parker T, Neparidze N, Bar N, Seropian S, Siddon A, Zeidan A. Isolated Trisomy 11 in Patients with Myeloid Malignancies - Is the Prognosis Not As Grim As Previously Thought? Blood 2019, 134: 5174-5174. DOI: 10.1182/blood-2019-127277.
  • Immune Checkpoint Inhibitor Therapy for Acute Myeloid Leukemia and Higher-Risk Myelodysplastic Syndromes: A Single-Center ExperienceShallis R, Bewersdorf J, Gowda L, Podoltsev N, Prebet T, Gore S, Halene S, Isufi I, Foss F, Huntington S, Kim T, Pillai M, Parker T, Neparidze N, Bar N, Seropian S, Zeidan A. Immune Checkpoint Inhibitor Therapy for Acute Myeloid Leukemia and Higher-Risk Myelodysplastic Syndromes: A Single-Center Experience Blood 2019, 134: 1330-1330. DOI: 10.1182/blood-2019-127422.
  • Loss of METTL3 Mediated m6A RNA Modification Results in Double-Stranded RNA Induced Innate Immune Response and Hematopoietic FailureGao Y, Vasic R, Song Y, Teng R, Gbyli R, Biancon G, Nelakanti R, Kudo E, Liu W, Ardasheva A, Fu X, Wang X, Joshi P, Dura B, Lee V, Viero G, Iwasaki A, Fan R, Xiao A, Flavell R, Li H, Tebaldi T, Halene S. Loss of METTL3 Mediated m6A RNA Modification Results in Double-Stranded RNA Induced Innate Immune Response and Hematopoietic Failure Blood 2019, 134: 450-450. DOI: 10.1182/blood-2019-130442.
  • The PRIME Trial: PARP Inhibition in IDH Mutant Effectiveness Trial. a Phase II Study of Olaparib in Isocitrate Dehydrogenase (IDH) Mutant Relapsed/Refractory Acute Myeloid Leukemia and Myelodysplastic SyndromeChandhok N, Wei W, Bindra R, Halene S, Shyr Y, Li J, Berens M, Karlovich C, Ivy S, Prebet T. The PRIME Trial: PARP Inhibition in IDH Mutant Effectiveness Trial. a Phase II Study of Olaparib in Isocitrate Dehydrogenase (IDH) Mutant Relapsed/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome Blood 2019, 134: 3909-3909. DOI: 10.1182/blood-2019-129168.
  • Ivo-Nivo: A Phase II Study of the IDH1 Inhibitor Ivosidenib (AG-120) in Combination with the Checkpoint Blockade Inhibitor Nivolumab for Patients with IDH1 Mutated Relapsed/Refractory AML and High Risk MDSChandhok N, Wei W, Halene S, Prebet T. Ivo-Nivo: A Phase II Study of the IDH1 Inhibitor Ivosidenib (AG-120) in Combination with the Checkpoint Blockade Inhibitor Nivolumab for Patients with IDH1 Mutated Relapsed/Refractory AML and High Risk MDS Blood 2019, 134: 1374-1374. DOI: 10.1182/blood-2019-130033.
  • PARP Inhibitors Are Effective in IDH1/2 Mutant MDS and AML Resistant to Targeted IDH InhibitorsGbyli R, Song Y, Liu W, Gao Y, Chandhok N, Fu X, Wang X, Patel A, Sundaram R, Tebaldi T, Biancon G, Ardasheva A, Qin A, Sadykov M, Mamillapalli P, Flavell R, Prebet T, Bindra R, Halene S. PARP Inhibitors Are Effective in IDH1/2 Mutant MDS and AML Resistant to Targeted IDH Inhibitors Blood 2019, 134: 4222-4222. DOI: 10.1182/blood-2019-130814.
  • U2AF1 Driver Mutations in Hematopoietic Disorders Alter but Do Not Abrogate RNA Binding and Enlighten Structural Dependencies of the U2AF-RNA ComplexBiancon G, Joshi P, Hunck T, Gao Y, Botti V, Qin A, Sadykov M, Wang X, Viero G, Neuenkirchen N, Taylor A, Huang J, Ardasheva A, Fu X, Lin H, Pillai M, Kielkopf C, Neugebauer K, Tebaldi T, Halene S. U2AF1 Driver Mutations in Hematopoietic Disorders Alter but Do Not Abrogate RNA Binding and Enlighten Structural Dependencies of the U2AF-RNA Complex Blood 2019, 134: 1230-1230. DOI: 10.1182/blood-2019-130759.
  • In Vivo reconstruction of Human Erythropoiesis with Circulating Mature Human RBCs in Humanized Liver Mistrg MiceSong Y, Shan L, Gbyli R, Liu W, Fu X, Wang X, Qin A, Patel A, Gao Y, Tebaldi T, Biancon G, Urbonas D, Alderman J, Halene S, Flavell R. In Vivo reconstruction of Human Erythropoiesis with Circulating Mature Human RBCs in Humanized Liver Mistrg Mice Blood 2019, 134: 338-338. DOI: 10.1182/blood-2019-130701.
  • The GPR68/BCL2 Axis Remodels Metabolism in AML By Relocating CalciumHe X, Hawkins C, Lawley L, Wunderlich M, Mizukawa B, Zha X, Halene S, Fang J. The GPR68/BCL2 Axis Remodels Metabolism in AML By Relocating Calcium Blood 2019, 134: 2661-2661. DOI: 10.1182/blood-2019-125455.
  • LAM-003, a Novel Oral Heat Shock Protein 90 Inhibitor for Treatment of Acute Myeloid Leukemia, Including Wild-Type and FMS-like Tyrosine Kinase 3 (FLT3)-Mutant DiseaseBeeharry N, Landrette S, Grotzke J, Gayle S, Hernandez M, Halene S, Young P, Miller L, Xu T, Rothberg J, Lichenstein H. LAM-003, a Novel Oral Heat Shock Protein 90 Inhibitor for Treatment of Acute Myeloid Leukemia, Including Wild-Type and FMS-like Tyrosine Kinase 3 (FLT3)-Mutant Disease Blood 2019, 134: 2664-2664. DOI: 10.1182/blood-2019-125770.
  • Variable Response to BCL2 Inhibition in MDS Is Enhanced across MDS Subtypes with Synergistic Combination of BCL2+MCL1 InhibitionFischer M, Arrate M, Childress M, Smith B, Song Y, Gbyli R, Stricker T, Halene S, Savona M. Variable Response to BCL2 Inhibition in MDS Is Enhanced across MDS Subtypes with Synergistic Combination of BCL2+MCL1 Inhibition Blood 2019, 134: 2982-2982. DOI: 10.1182/blood-2019-126578.
  • Low Iron Promotes Megakaryocytic Commitment of Megakaryocytic-Erythroid Progenitors in Human and MiceXavier-Ferrucio J, Li X, Scanlon V, Zhang P, Ayala-Lopez N, Tebaldi T, Halene S, Finberg K, Krause D. Low Iron Promotes Megakaryocytic Commitment of Megakaryocytic-Erythroid Progenitors in Human and Mice Blood 2018, 132: 2-2. DOI: 10.1182/blood-2018-99-115124.
  • Mettl3 Mediated m6A Modification Is Essential in Fetal HematopoiesisGao Y, Vasic R, Tebaldi T, Song Y, Teng R, Joshi P, Viero G, Xiao A, Batista P, Li H, Flavell R, Halene S. Mettl3 Mediated m6A Modification Is Essential in Fetal Hematopoiesis Blood 2018, 132: 3825-3825. DOI: 10.1182/blood-2018-99-119699.
  • Proton Sensor GPR68 Is Essential to Maintain Myeloid MalignanciesHe X, Wunderlich M, Mizukawa B, Mulloy J, Feng S, Lawley L, Hawkins C, Fan W, Zhou G, Zha X, Zhang J, Hodge J, Fan D, Halene S, Fang J. Proton Sensor GPR68 Is Essential to Maintain Myeloid Malignancies Blood 2018, 132: 1353-1353. DOI: 10.1182/blood-2018-99-110399.
  • Whole Exome Sequencing and Extended Thrombophilia Testing in Patients with Venous ThromboembolismShevell L, Lee E, Dhodapkar R, Dykas D, Popa A, Ma D, Bar N, Baluha A, Burns A, Ochoa Chaar C, Dupont A, Gu S, Halene S, Luciano R, Marien R, Neparidze N, Parker T, Yao X, Camire R, Ebberink E, Garcia de Frutos P, Gnanasambandan K, Sayeski P, Huntington J, Lentz S, Mertens K, Parish C, Rezaie R, Connors J, Leavitt A, Bale A, Lee A. Whole Exome Sequencing and Extended Thrombophilia Testing in Patients with Venous Thromboembolism Blood 2018, 132: 2506-2506. DOI: 10.1182/blood-2018-99-115529.
  • Role of RNA Binding Protein RBM15 in m6A RNA Methylation During Megakaryocytic DifferentiationAyala‐Lopez N, Ross R, Halene S, Limbach P, Krause D. Role of RNA Binding Protein RBM15 in m6A RNA Methylation During Megakaryocytic Differentiation The FASEB Journal 2018, 32: 790.9-790.9. DOI: 10.1096/fasebj.2018.32.1_supplement.790.9.
  • Production of 2-Hydroxyglutarate by IDH Mutant Malignancies Induces a BRCAness State That Can be Exploited By PARP Inhibitors and RadiationCorso C, Bindra R, Glazer P, Sulkowski P, Robinson N, Scanlon S, Purshouse K, Bai H, Liu Y, Sundaram R, Hegan D, Fons N, Breuer G, Song Y, Mishra-Gorur K, De Feyter H, de Graaf R, Surovtseva Y, Kachman M, Halene S, Gunel M. Production of 2-Hydroxyglutarate by IDH Mutant Malignancies Induces a BRCAness State That Can be Exploited By PARP Inhibitors and Radiation International Journal Of Radiation Oncology • Biology • Physics 2017, 99: e68. DOI: 10.1016/j.ijrobp.2017.06.754.
  • Abstract LB-290: Oncometabolites induce a BRCAness state that can be exploited by PARP inhibitorsSulkowski P, Corso C, Robinson N, Scanlon S, Purshouse K, Bai H, Liu Y, Sundaram R, Hegan D, Fons N, Breuer G, Song Y, Mishra K, Feyter H, Graaf R, Surovtseva Y, Kachman M, Halene S, Gunel M, Glazer P, Bindra R. Abstract LB-290: Oncometabolites induce a BRCAness state that can be exploited by PARP inhibitors Cancer Research 2017, 77: lb-290-lb-290. DOI: 10.1158/1538-7445.am2017-lb-290.
  • Functional Consequences of Spliceosome MutationsHalene S. Functional Consequences of Spliceosome Mutations Blood 2016, 128: sci-18-sci-18. DOI: 10.1182/blood.v128.22.sci-18.sci-18.
  • Whole Exome Sequencing in Evaluation of Thrombophilia: A Novel 33-Gene PanelLee E, Dykas D, Bale A, Cromwell C, Parker T, Halene S, Burns A, Yao X, Lee A. Whole Exome Sequencing in Evaluation of Thrombophilia: A Novel 33-Gene Panel Blood 2015, 126: 3529-3529. DOI: 10.1182/blood.v126.23.3529.3529.
  • Efficient Engraftment and Disease Replication of Myelodysplastic Syndromes Using a Novel Humanized Mice ModelSong Y, Taylor A, Rongvaux A, Jiang T, Podoltsev N, Xu M, Neparidze N, Torres R, Barbarotta L, Balasubramanian K, Finberg K, Kluger Y, Flavell R, Halene S. Efficient Engraftment and Disease Replication of Myelodysplastic Syndromes Using a Novel Humanized Mice Model Blood 2015, 126: 4100-4100. DOI: 10.1182/blood.v126.23.4100.4100.
  • Next Generation Sequencing Identifies a Novel Subset of Non-Down Syndrome Acute Megakaryoblastic Leukemia Characterized By Chimeric Transcripts Involving HOX Cluster Genesde Rooij J, Branstetter C, Ma J, Li Y, Cheng J, Koss C, Easton J, Verboon L, Mulder H, Rusch M, Lim J, Reinhardt K, Yeoh A, Shih L, Liang D, Halene S, Krause D, Zhang J, Downing J, Locatelli F, Reinhardt D, van den Heuvel-Eibrink M, Forenerod M, Zwaan C, Gruber T. Next Generation Sequencing Identifies a Novel Subset of Non-Down Syndrome Acute Megakaryoblastic Leukemia Characterized By Chimeric Transcripts Involving HOX Cluster Genes Blood 2015, 126: 171-171. DOI: 10.1182/blood.v126.23.171.171.
  • Integrative Genome-Wide Analysis of RNA Binding and Splicing Reveals Complex Loss and Gain of Function Alterations By SRSF2 P95 Mutations in MyelodysplasiaRejeski K, Liang Y, Tebaldi T, Stefani G, Taylor A, Maziarz J, Song Y, Balasubramanian K, Vasic R, Kapetanovic E, Abdel-Wahab O, Pillai M, Halene S. Integrative Genome-Wide Analysis of RNA Binding and Splicing Reveals Complex Loss and Gain of Function Alterations By SRSF2 P95 Mutations in Myelodysplasia Blood 2015, 126: 141-141. DOI: 10.1182/blood.v126.23.141.141.
  • Developing a Model of Human Pluripotent to Hematopoietic Stem Cell Development in Mistrg MiceAstle J, Xiang Y, Rongvaux A, Weibel C, Elizabeth H, Halene S, Park I, Flavell R. Developing a Model of Human Pluripotent to Hematopoietic Stem Cell Development in Mistrg Mice Blood 2015, 126: 4755-4755. DOI: 10.1182/blood.v126.23.4755.4755.
  • 26 HUMANIZED MICE AFFORD EFFICIENT ENGRAFTMENT AND DISEASE REPLICATION OF MYELODYSPLASTIC SYNDROMESSong Y, Rongvaux A, Taylor A, Podoltsev N, Xu M, Neparidze N, Torres R, Barbarotta L, Balasubramanian K, Finberg K, Flavell R, Halene S. 26 HUMANIZED MICE AFFORD EFFICIENT ENGRAFTMENT AND DISEASE REPLICATION OF MYELODYSPLASTIC SYNDROMES Leukemia Research 2015, 39: s11-s12. DOI: 10.1016/s0145-2126(15)30027-8.
  • 22 MUTATIONS IN SRSF2 IDENTIFIED IN MYELODYSPLASIA AFFECT RNA BINDING AFFINITY, SPECIFICITY, AND SPLICINGLiang Y, Liang Y, Daubner G, Daubner G, Tebaldi T, Li Y, Li Y, Stefani G, Stefani G, Taylor A, Taylor A, Maziarz J, Maziarz J, Rejeski K, Rejeski K, Vasic R, Vasic R, Modis Y, Modis Y, Allain F, Allain F, Halene S. 22 MUTATIONS IN SRSF2 IDENTIFIED IN MYELODYSPLASIA AFFECT RNA BINDING AFFINITY, SPECIFICITY, AND SPLICING Leukemia Research 2015, 39: s9-s10. DOI: 10.1016/s0145-2126(15)30023-0.
  • Epithelial (E)-Cadherin Is a Novel Regulator of Platelet FunctionKrause D, Halene S, Booth C, Jin H, Zou S, Teixeira A, Zhang P. Epithelial (E)-Cadherin Is a Novel Regulator of Platelet Function Blood 2014, 124: 95-95. DOI: 10.1182/blood.v124.21.95.95.
  • Tmod3 participates in platelet formation and sizing in mouse fetal liver (278.9)Sui Z, Robeta N, Sanada C, Halene S, Krause D, Fowler V. Tmod3 participates in platelet formation and sizing in mouse fetal liver (278.9) The FASEB Journal 2014, 28 DOI: 10.1096/fasebj.28.1_supplement.278.9.
  • Srf Is Required For Neutrophil Migration In Response To InflammationTaylor A, Tang W, Bruscia E, Zhang P, Lin A, Gaines P, Vu L, Wu D, Halene S. Srf Is Required For Neutrophil Migration In Response To Inflammation Blood 2013, 122: 319-319. DOI: 10.1182/blood.v122.21.319.319.
  • P-225 Modeling of myelodysplasia in a humanized immunodeficient mouse modelHalene S, Rongvaux A, Podoltsev N, Kahlon K, Manz M, Flavell R. P-225 Modeling of myelodysplasia in a humanized immunodeficient mouse model Leukemia Research 2013, 37: s124-s125. DOI: 10.1016/s0145-2126(13)70272-8.
  • Regional variation in treatment costs and survival for elderly patients with myelodysplastic syndromes.Ma X, Wang R, Long J, Gold H, Halene S, Gross C. Regional variation in treatment costs and survival for elderly patients with myelodysplastic syndromes. Journal Of Clinical Oncology 2012, 30: 6628-6628. DOI: 10.1200/jco.2012.30.15_suppl.6628.
  • Serum Response Factor Is An Essential Transcription Factor in Megakaryocytic Maturation.Halene S, Gao Y, Hahn K, Smith E, Lin S, Perkins A, Krause D. Serum Response Factor Is An Essential Transcription Factor in Megakaryocytic Maturation. Blood 2009, 114: 3652-3652. DOI: 10.1182/blood.v114.22.3652.3652.
  • Transcriptional Regulation of the Nuclear Envelope Lamin B Receptor: New Roles for GA Binding Protein (GABP) in Neutrophil Development.Garhwal R, Rosmarin A, Halene S, Gaines P. Transcriptional Regulation of the Nuclear Envelope Lamin B Receptor: New Roles for GA Binding Protein (GABP) in Neutrophil Development. Blood 2009, 114: 1464-1464. DOI: 10.1182/blood.v114.22.1464.1464.
  • Nucleophosmin-1 Interacts with CCAAT Enhancer Binding Protein Alpha (C/EBPα) to Facilitate Granulocyte Maturation: Implications in MDS and AML.Khanna-Gupta A, Chen J, Silver M, Sun H, Abayasekara N, Halene S, Sportoletti P, Pandolfi P, Berliner N. Nucleophosmin-1 Interacts with CCAAT Enhancer Binding Protein Alpha (C/EBPα) to Facilitate Granulocyte Maturation: Implications in MDS and AML. Blood 2009, 114: 2768-2768. DOI: 10.1182/blood.v114.22.2768.2768.
  • OTT-MKL1 and MKL1 Inhibit Wnt Signaling.Halene S, Cheng E, Schulz V, Tuck D, Krause D. OTT-MKL1 and MKL1 Inhibit Wnt Signaling. Blood 2008, 112: 2250-2250. DOI: 10.1182/blood.v112.11.2250.2250.
  • Generation of a Factor Dependent Myeloid Cell Line from Nucleophosmin-1 Heterozygous (NPM-1+/−) Mouse Bone Marrow as a Model for 5q- MDSKhanna-Gupta A, Sun H, Chen J, Halene S, Sportoletti P, Pandolfi P, Berliner N. Generation of a Factor Dependent Myeloid Cell Line from Nucleophosmin-1 Heterozygous (NPM-1+/−) Mouse Bone Marrow as a Model for 5q- MDS Blood 2008, 112: 852-852. DOI: 10.1182/blood.v112.11.852.852.
  • Dynamic Expression of the Lamin B Receptor and Associated Proteins during Myeloid Differentiation: Insight into Mechanisms of Neutrophil Vs. Macrophage MorphogenesisGaines P, Gotur D, Halene S, Olins A, Olins D. Dynamic Expression of the Lamin B Receptor and Associated Proteins during Myeloid Differentiation: Insight into Mechanisms of Neutrophil Vs. Macrophage Morphogenesis Blood 2008, 112: 3546-3546. DOI: 10.1182/blood.v112.11.3546.3546.
  • Identification of Common Molecular Pathways in Granulopoiesis Associated with C/EBP Epsilon and Gfi-1-Deficient Neutrophil Specific Granule Deficiency (SGD).Khanna-Gupta A, Halene S, Sun H, Dahl R, Boxer L, Berliner N. Identification of Common Molecular Pathways in Granulopoiesis Associated with C/EBP Epsilon and Gfi-1-Deficient Neutrophil Specific Granule Deficiency (SGD). Blood 2006, 108: 1196-1196. DOI: 10.1182/blood.v108.11.1196.1196.
  • C/EBPε Knockout (KO) EML and PBiIM Cell Lines Replicate the In Vivo Phenotype of the C/EBPε KO Mouse.Halene S, Gaines P, Zibello T, Williams S, Khanna-Gupta A, Berliner N. C/EBPε Knockout (KO) EML and PBiIM Cell Lines Replicate the In Vivo Phenotype of the C/EBPε KO Mouse. Blood 2005, 106: 2725-2725. DOI: 10.1182/blood.v106.11.2725.2725.

Clinical Trials

ConditionsStudy Title
Myeloid and Monocytic LeukemiaAn Exploratory Phase 1b Open-label Multi-arm Trial to Evaluate the Safety and Efficacy of CC-90009 in Combination With Anti-Leukemia Agents in Subjects With Acute Myeloid Leukemia
Leukemia, other; Myeloid and Monocytic LeukemiaA Phase 3, Randomized, Double-blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAKi Treatment Naive MF Patients
Leukemia, not otherwise specified; Leukemia, otherBLockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease in Acute Myeloid Leukemia 2 (BLAST MRD AML-2): A Randomized Phase 2 Study of the Venetoclax, Azacitadine, and Pembrolizumab (VAP) Versus Venetoclax and Azacitadine as First Line Therapy in Older Patients With Acute Myeloid Leukemia (AML) Who Are Ineligible or Who Refuse Intensive Chemotherapy
Myeloid and Monocytic LeukemiaBLockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease in Acute Myeloid Leukemia 1 (BLAST MRD AML-1): A Randomized Phase 2 Study of the Anti-PD-1 Antibody Pembrolizumab in Combination With Conventional Intensive Chemotherapy as Frontline Therapy in Patients With Acute Myeloid Leukemia
Leukemia, otherA Study to Evaluate Imetelstat (GRN163L) in Transfusion-Dependent Subjects With IPSS Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) That is Relapsed/Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment
Myeloid and Monocytic LeukemiaThe PRIME Trial: PARP Inhibition in IDH Mutant Effectiveness Trial. A Phase II Study of Olaparib in Isocitrate Dehydrogenase (IDH) Mutant Relapsed/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome
Leukemia, otherPhase III Randomized Study of Crenolanib Versus Midostaurin Administered Following Induction Chemotherapy and Consolidation Therapy in Newly Diagnosed Subjects With FLT3 Mutated Acute Myeloid Leukemia
Leukemia, not otherwise specified; Leukemia, otherA Phase IB/II Study of Venetoclax (ABT-199) in Combination With Liposomal Vincristine in Patients With Relapsed or Refractory T-Cell or B-Cell Acute Lymphoblastic Leukemia
Leukemia, not otherwise specified; Leukemia, otherPhase II Study of Adding the Anti-PD-1 Pembrolizumab to Tyrosine Kinase Inhibitors in Patients With Chronic Myeloid Leukemia and Persistently Detectable Minimal Residual Disease
Lymphoid LeukemiaA Phase 2 Study of the JAK1/JAK2 Inhibitor Ruxolitinib With Chemotherapy in Children With De Novo High-Risk CRLF2-Rearranged and/or JAK Pathway-Mutant Acute Lymphoblastic Leukemia
Myeloid and Monocytic LeukemiaA Phase 1, Open-label, Dose Finding Study of CC-90009 in Subjects With Relapsed, Refractory Acute Myeloid Leukemia