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Stephanie Halene, MD, PhD

Associate Professor of Medicine (Hematology); Chief, 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

Clinical Trials

ConditionsStudy Title
Leukemia, not otherwise specified; Leukemia, other; Myeloid and Monocytic LeukemiaA Randomized, Double-blind, Placebo-controlled Phase III Multi-center Study of Azacitidine With or Without MBG453 for the Treatment of Patients With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2)
Leukemia, not otherwise specified; Leukemia, other; Myeloid and Monocytic LeukemiaA Randomized, Double-Blind, Phase 3 Study Evaluating the Safety and Efficacy of Venetoclax in Combination With Azacitidine in Patients Newly Diagnosed With Higher-Risk Myelodysplastic Syndrome (Higher-Risk MDS)
Myeloid and Monocytic LeukemiaA Phase 1, Parallel, Open-Label Study of the Safety and Tolerability, Pharmacokinetics, and Antileukemic Activity of ASTX660 as a Single Agent and in Combination With ASTX727 in Subjects With Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)
Leukemia, otherPhase 1B Study of PTC299 in Relapsed/Refractory Acute Leukemias
Leukemia, otherA Phase II Multi-center, Single Arm, Safety and Efficacy Study of MBG453 in Combination With Azacitidine and Venetoclax for the Treatment of Acute Myeloid Leukemia (AML) in Adult Patients Unfit for Chemotherapy
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
Multiple MyelomaA Phase 1, Open-label, Dose Finding Study of CC-93269, a BCMA X CD3 T Cell Engaging Antibody, in Subjects With Relapsed and Refractory Multiple Myeloma.
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, otherA Randomized Phase II/III Study of Conventional Chemotherapy +/- Uproleselan (GMI-1271) in Older Adults With Acute Myeloid Leukemia Receiving Intensive Induction Chemotherapy
Leukemia, not otherwise specified; Leukemia, other; Myeloid and Monocytic LeukemiaA Phase 3, Double-blind, Randomized Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) Versus Placebo for the Treatment of Anemia Due to the IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes in Subjects With Ring Sideroblasts Who Require Red Blood Cell Transfusions.
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
Lymphoid LeukemiaA Phase 1 Study of Blinatumomab in Combination With Checkpoint Inhibitor(s) of PD-1 (Nivolumab) or Both PD-1 (Nivolumab) and CTLA-4 (Ipilimumab) in Patients With Poor-Risk, Relapsed or Refractory CD19+ Precursor B-Lymphoblastic 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
Multiple MyelomaGlobal Response Assessment by Advanced Imaging and Myeloma Lesion Biopsies During Induction Therapy of Multiple Myeloma with Carfilzomib Lenalidomide Dexamethasone (CRD)
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
Leukemia, otherAn Open-Label, Randomized, Phase 2 Dose-Finding Study of Pacritinib in Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis Previously Treated With Ruxolitinib
Myeloid and Monocytic LeukemiaA Phase 1, Open-label, Dose Finding Study of CC-90009 in Subjects With Relapsed, Refractory Acute Myeloid Leukemia
Leukemia, not otherwise specified; Leukemia, otherA Phase I-II Randomized Trial of a Combination of Nintedanib/Placebo in Combination With Induction Chemotherapy for Patients With Refractory or First Relapse Acute Myeloid Leukemia