Edward J. Benz Jr., MD
Richard and Susan Smith Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Harvard Medical School
Office phone: 617-632-4266
Preferred contact method: office phone
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Area of ResearchThe Molecular Pathology of Hemolytic Anemias
Dana-Farber Cancer Institute
450 Brookline Avenue
Boston, MA 02215
BiographyDr. Benz graduated from Harvard Medical School in 1973 and received his training at Brigham and Women's Hospital and the National Institutes of Health. He is president of Dana-Farber Cancer Institute, CEO of Dana-Farber/Partners CancerCare, director and principal investigator of Dana-Farber/Harvard Cancer Center, and a member of the Governing Board of Dana-Farber/Children's Cancer Center. He is also a clinical hematologist and an active NIH-funded investigator.
- President, American Association of Cancer Institutes, 2005
- Elected Fellow, American Association for the Advancement of Science, 2004
- Member, American Academy of Arts and Sciences, 2004
- Member, Institute of Medicine, 2004
ResearchThe Molecular Pathology of Hemolytic Anemias
Our laboratory continues to focus on the molecular pathology and physiology of red cell development, the molecular basis of inherited hemolytic anemias, and the use of the red cell homeostatic system as a model to study gene regulation and growth control in other tissues.
During the past five years, we have focused on the structure, function, gene regulation, and molecular pathology of protein 4.1. This cytoskeletal protein, originally described in the red cell, forms a ternary complex with spectrin-actin, and attaches the spectrin latticework to membranes by binding to the cytoplasmic domains of key transmembrane proteins. Defects in this protein are associated with hereditary erythrocytosis. Our laboratory has shown that many isoforms of protein 4.1 arise from a single protein 4.1R gene by tissue-specific alternative mRNA splicing pathways, a number of which we have characterized. Our group has identified at least three target sequence areas and one putative splicing factor involved in tissue-specific regulation of red cell isoforms during erythroid differentiation.
Isoforms of protein 4.1R are expressed in many tissues and exhibit complex patterns of intracellular localization. We have shown that some forms associate with NuMa, a key mitotic protein, and are components of the mitotic apparatus. Other domains of protein 4.1R participate in tight junction formation by binding the proteins ZO-2. Moreover, as cells approach the state of terminal differentiation, there is a clear shift from the intranuclear localization of protein 4.1R to peripheral localization. Current studies are pursuing the hypothesis that this complex shift in localization and association is indicative of a role for protein 4.1R in signaling terminal differentiation and initiating shutdown of cell proliferation and division.
- Yang G, Huang SC, Wu JY, Benz EJ Jr. An erythroid differentiation-specific splicing switch in protein 4.1R mediated by the interaction of SF2/ASF with an exonic splicing enhancer. Blood 2005;105:2146-53.
- Huang SC, Liu ES, Chan SH, Munagala ID, Cho HT, Jagadeeswaran R, Benz EJ Jr. Mitotic regulation of protein 4.1R involves phosphorylation by cdc2 kinase. Mol Biol Cell 2005;16:117-27.
- Huang SC, Jagadeeswaran R, Liu ES, Benz EJ Jr. Protein 4.1R, a microtubule-associated protein involved in microtubule aster assembly in mammalian mitotic extract. J Biol Chem 2004;279:34595-602.
- Benz EJ Jr. Genotypes and phenotypes-another lesson from the hemoglobinopathies. N Engl J Med 2004;351:1490-2.
- Yang, Guang, PhD
- Zhou, AnYu, PhD