Stephanie Halene, MD, Dr Med
Arthur H and Isabel Bunker Professor of Medicine (Hematology) and Professor of PathologyCards
About
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 Research Interests
Academic Achievements & Community Involvement
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
News & Links
News
- December 18, 2024
Yale research advances presented at American Society of Hematology annual meeting
- December 04, 2024
Accolades, Awards & Honors
- September 05, 2024
Five Yale Investigators Receive NIH U01 Award
- August 12, 2024
Protein in Mosquito Saliva Inhibits Host Immune Response