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Stephanie Halene, MD, Dr Med

Arthur H and Isabel Bunker Professor of Medicine (Hematology) and Professor of Pathology
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Additional Titles

Chief, Department of Internal Medicine, Section of Hematology

Director, DeLuca Center for Innovation in Hematology Research, Yale Cancer Center

Assistant Medical Director CRSL, Yale Cancer Center

Chief, Yale Cancer Center, Division of Translational Hematology

Halene Lab

The Halene Laboratory focuses on the study of myeloid malignancies and hematopoiesis.

About

Titles

Arthur H and Isabel Bunker Professor of Medicine (Hematology) and Professor of Pathology

Chief, Department of Internal Medicine, Section of Hematology; Director, DeLuca Center for Innovation in Hematology Research, Yale Cancer Center; Assistant Medical Director CRSL, Yale Cancer Center; Chief, Yale Cancer Center, Division of Translational Hematology

Biography

Dr. Halene is a physician-scientist who received her MD degree at Eberhardt-Karls-University in Tübingen, Germany. She subsequently completed a postdoctoral fellowship in the laboratory of Donald B. Kohn at CHLA in Los Angeles and her residency in internal medicine in the traditional program at Yale New Haven Hospital. She completed her fellowship in hematology/oncology at Yale and joined the ladder faculty at YSM as an assistant professor in 2010. At that time she was also named director of the Hematology Tissue Bank for Yale Cancer Center. She was promoted to associate professor in 2016 and subsequently served as interim chief of the Section of Hematology prior to her appointment as chief of that section in 2020.

Her laboratory studies hematopoiesis and myelopoiesis and in particular how mutations in splicing factors and perturbations in RNA modifications contribute to hematologic malignancies such as myelodysplasia and leukemia. Dr. Halene, in collaboration with the Flavell laboratory in the YSM Department of Immunobiology, has developed the first efficient xenotransplantation model in humanized mice to study myelodysplasia and enable testing of novel drug treatments. Dr. Halene’s research has garnered significant attention from the international community, as evidenced by numerous invited speaking engagements, an invitation to serve as a section editor on myeloid malignancies for a major journal, and publications in top tier journals in her field. In 2015 she was presented with the Sir William Osler Young Investigator Award and in 2019 was elected a member of the Interurban Clinical Club.

Dr. Halene is director of the DeLuca Center for Innovation in Hematology Research. Through generous funding from The Frederick A. DeLuca Foundation, the center has established a comprehensive biospecimen bank, awarded pilot and career development grant funding to advance cutting-edge discoveries in hematologic malignancies and classical hematologic disorders.

Meet Dr. Stephanie Halene>>

Appointments

Education & Training

Fellow
Yale University School of Medicine (2006)
Resident
Yale-New Haven Hospital (2002)
Postdoctoral Associate
Childrens Hospital Los Angeles (2000)
Dr Med
Eberhard-Karls-Universitat Tubingen (1997)
Resident
Eberhard-Karls-University (1997)
MD
Eberhard-Karls-Universitat Tubingen (1995)

Research

Overview

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.

Medical Subject Headings (MeSH)

Adult Stem Cells; Aging; Alternative Splicing; Hematopoiesis; Hematopoietic Stem Cells; Immunity, Innate; Immunotherapy; Leukemia; Leukemia, Myelomonocytic, Chronic; Methylation; Myelodysplastic Syndromes; RNA Processing, Post-Transcriptional; RNA Splicing; RNA-Binding Proteins; Single-Cell Analysis; Stress Granules; Xenograft Model Antitumor Assays

Publications

Featured Publications

Academic Achievements & Community Involvement

  • activity

    External Advisory Board, Cellular & Molecular Biology Masters Program

  • honor

    Elected Member

  • honor

    2022 Recipient of the "2nd Century of Women: Emerging Leaders in Internal Medicine" Award

  • activity

    Music Haven. A non-profit organization providing free string instrument lesson and music education to children in New Haven Public Schools (http://musichavenct.org)

  • honor

    Elected Member

Clinical Care

Overview

Stephanie Halene, MD, is chief of hematology at Yale Cancer Center and Smilow Cancer Hospital, and says she enjoys the close relationships she forms with patients and the detective work that is often involved in her clinical care and research.

“Hematology has two aspects: malignant disorders, such as leukemia and lymphoma, and what we call benign or classical hematologic disorders,” Dr. Halene says. “Either way, patients can be very sick, and it takes a lot of piecing clues together and working with other specialists to understand what is going on.”

Dr. Halene is a physician-scientist who studies hematopoiesis (formation of new blood cells) and myelopoiesis (production of bone marrow or bone marrow cells) and how RNA modifications contribute to leukemia and myelodysplastic syndromes (conditions caused by blood-forming cells in the bone marrow that become abnormal).

“My research is broad. Whereas some scientists go after a pathway or a certain approach, everything I do comes back to understanding hematopoiesis and that malignant transformation,” she says. “My work is also very collaborative as we can harness our scientific findings to advance our understanding and care of myelodysplastic syndromes.”

Dr. Halene says the field of hematology is ripe for continued advances. “I don’t think the speed of new discoveries has ever been better than it is now. There have been many incredible advances in technology to better understand the mechanisms of disease and several new agents to treat disease,” she says.

She is also director of the DeLuca Center for Innovation in Hematology Research, which has established a comprehensive biospecimen bank and awarded grant funding to advance discoveries in hematologic malignancies and classical hematologic disorders.

Clinical Specialties

Hematology; Leukemia & Lymphoma

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