Stephanie Halene, MD, PhD

Associate Professor of Medicine (Hematology)

Research Departments & Organizations

Internal Medicine: Hematology: Halene Lab

Center for RNA Science and Medicine

Yale Cancer Center: Genomics, Genetics, and Epigenetics

Yale Stem Cell Center

Office of Cooperative Research

Research Interests

Alternative Splicing; Hematopoiesis; Leukemia; Myelodysplastic Syndromes; Myelopoiesis; Xenograft Model Antitumor Assays

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. 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; RNA splicing

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 AMLs. Mutations in SFs are not only recurrent in nature, affecting specific amino acid positions, but also mutually exclusive, i.e. patients carry mutations in only one splicing factor. This suggests a common mechanism in the pathogenesis of MDS. We employ structural, molecular biology, and in vivo techniques to determine disease mechanism and develop novel therapeutics.

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.

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.

Clinical Trials

Conditions Study Title
Leukemia, other Phase 1b Dose Escalation followed by Phase 2 treatment. Participants will be evaluable for inclusion in the Phase 1b and Phase 2 portions of the study if they receive at least one dose of protocol therapy.
Leukemia, not otherwise specified, Leukemia, other, Myeloid and Monocytic Leukemia A 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, other Phase 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, other An International Phase Ib Multicentre Study to Characterize the Safety and Tolerability of Intravenously Administered S64315 a Selective Mcl-1 Inhibitor, in Combination With Orally Administered Venetoclax a Selective Bcl-2 Inhibitor in Patients With Acute Myeloid Leukaemia
Lymphoid Leukemia A 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, other A 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, other Phase 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
Leukemia, other, Myeloid and Monocytic Leukemia A Phase 1b Study Evaluating the Safety and Pharmacokinetics of Venetoclax as a Single-Agent and in Combination With Azacitidine in Subjects With Relapsed/Refractory Myelodysplastic Syndromes
Multiple Myeloma Global Response Assessment by Advanced Imaging and Myeloma Lesion Biopsies During Induction Therapy of Multiple Myeloma with Carfilzomib Lenalidomide Dexamethasone (CRD)
Myeloid and Monocytic Leukemia Phase I, International, Multicentre, Open-label, Non-randomised, Non-comparative Study of Intravenously Administered S64315, a Mcl-1 Inhibitor, in Patients With Acute Myeloid Leukaemia (AML) or Myelodysplastic Syndrome (MDS)
Leukemia, other An Open-Label, Phase I, Dose-Escalation Study Evaluating the Safety and Tolerability of DCLL9718S in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) or DCLL9718S in Combination With Azacitidine in Patients With Previously Untreated AML Unsuitable for Intensive Induction Chemotherapy
Myeloid and Monocytic Leukemia A Phase 1 Dose-Escalation Study of LAM-003 in Patients With Acute Myeloid Leukemia
Myeloid and Monocytic Leukemia A Phase 1b/2 Study of PCM-075 in Combination With Either Low-Dose Cytarabine or Decitabine in Subjects With Acute Myeloid Leukemia (AML)
Myeloid and Monocytic Leukemia The National Myelodysplastic Syndromes Natural History Study
Myeloid and Monocytic Leukemia A Randomized Phase II Trial to Simultaneously Evaluate Two Schedules of the Histone Deacetylase Inhibitor Entinostat in Combination With 5-Azacytidine (5AC, NSC 102816) in Elderly Patients With Acute Myeloid Leukemia (AML)
Myeloid and Monocytic Leukemia A Phase 1, Open-label, Dose Finding Study of CC-90009 in Subjects With Relapsed, Refractory Acute Myeloid Leukemia
Leukemia, not otherwise specified, Leukemia, other, Myeloid and Monocytic Leukemia A Multicenter, Pivotal Phase 3 Study of Iomab-B Prior to Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care in Older Subjects With Active, Relapsed or Refractory Acute Myeloid Leukemia
Leukemia, other A Phase 1b Study of the Anti-PD1 Antibody Pembrolizumab in Combination With the Histone Deacetylase Inhibitor, Entinostat for Treatment of Patients With Myelodysplastic Syndromes After DNA Methyltransferase Inhibitor Therapy Failure
Myeloid and Monocytic Leukemia A Phase 1/1b, Multicenter, Open-label, Dose-Escalation Study of FT-2102 as a Single Agent and in Combination With Azacitidine in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome With an IDH1 Mutation
Leukemia, not otherwise specified, Leukemia, other A 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

Selected Publications

See list of PubMed publications

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