Photo of Edward J. Benz,   MD

Edward J. Benz, MD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-4266
Fax: (617) 632-2161


edward_benz@dfci.harvard.edu

Photo of Edward J. Benz,   MD

Dana-Farber Cancer Institute
Phone: (617) 632-4266
Fax: (617) 632-2161


edward_benz@dfci.harvard.edu

Edward J. Benz, MD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Professor, Pediatrics, Harvard Medical School
  • Richard and Susan Smith Professor, Medicine, Harvard Medical School
  • Professor, Genetics, Harvard Medical School
  • President, Office of the President, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

DF/HCC ASSOCIATIONS

  • Member, Center Scientific Council
  • President, DFCI, Governance Committee
  • Director, Dana-Farber/Harvard Cancer Center, Executive Committee

Research Abstract

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 spectrinactin, 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 a component 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.

Publications

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  • Benz EJ. Learning about genomics and disease from the anucleate human red blood cell. J Clin Invest 2010; 120:4204-6. PubMed
  • Levit L, Smith AP, Benz EJ, Ferrell B. Ensuring quality cancer care through the oncology workforce. J Oncol Pract 2010; 6:7-11. PubMed
  • Huang SC, Cho A, Norton S, Liu ES, Park J, Zhou A, Munagala ID, Ou AC, Yang G, Wickrema A, Tang TK, Benz EJ. Coupled transcription-splicing regulation of mutually exclusive splicing events at the 5' exons of protein 4.1R gene. Blood 2009; 114:4233-42. PubMed
  • Bates SE,Benz EJ Jr. Commentary: troublesome words, linguistic precision, and medical oncology. Oncologist 2009; 14:445-7. PubMed
  • Zhou A,Ou AC,Cho A,Benz EJ Jr,Huang SC. Novel splicing factor RBM25 modulates Bcl-x pre-mRNA 5' splice site selection. Mol Cell Biol 2008; 28:5924-36. PubMed
  • Yang G, Huang SC, Wu JY, Benz EJ Jr. Regulated Fox-2 isoform expression mediates protein 4.1R splicing during erythroid differentiation. Blood 2007; 111:392-401. PubMed
  • Benz EJ Jr, Nathan DG, Amaravadi RK, Danial NN. Targeting the cell death-survival equation. Clin Cancer Res 2007; 13:7250-3. PubMed
  • Emmons KM, Burns White K, Benz EJ. Development of an integrated approach to cancer disparities: one cancer center's experience. Cancer Epidemiol Biomarkers Prev 2007; 16:2186-92. PubMed
  • Yang G, Huang SC, Wu JY, Benz EJ. An erythroid differentiation-specific splicing switch in protein 4.1R mediated by the interaction of SF2/ASF with an exonic splicing enhancer. Blood 2004; 105:2146-53. PubMed
  • Huang SC, Liu ES, Chan SH, Munagala ID, Cho HT, Jagadeeswaran R, Benz EJ. Mitotic regulation of protein 4.1R involves phosphorylation by cdc2 kinase. Mol Biol Cell 2004; 16:117-27. PubMed
  • Benz EJ. Genotypes and phenotypes--another lesson from the hemoglobinopathies. N Engl J Med 2004; 351:1490-2. PubMed
  • Huang SC, Jagadeeswaran R, Liu ES, Benz EJ. Protein 4.1R, a microtubule-associated protein involved in microtubule aster assembly in mammalian mitotic extract. J Biol Chem 2004; 279:34595-602. PubMed
  • Delhommeau F, Vasseur-Godbillon C, Leclerc P, Schischmanoff PO, Croisille L, Rince P, Morini. A splicing alteration of 4.1R pre-mRNA generates 2 protein isoforms with distinct assembly to spindle poles in mitotic cells. Blood 2002; 100:2629-36. PubMed
  • Deguillien M, Huang SC, Morini. Multiple cis elements regulate an alternative splicing event at 4.1R pre-mRNA during erythroid differentiation. Blood 2001; 98:3809-16. PubMed
  • Nathan D, Benz EJ. Comprehensive cancer centres and the war on cancer. Nat Rev Cancer 2002; 1:240-5. PubMed
  • Huang S, Lichtenauer UD, Pack S, Wang C, Kim AC, Lutchman M, Koch CA, Torres-Cruz J, Huang SC, Benz EJ, Christiansen H, Dockhorn-Dworniczak B, Poremba C, Vortmeyer AO, Chishti AH, Zhuang Z. Reassignment of the EPB4.1 gene to 1p36 and assessment of its involvement in neuroblastomas. Eur J Clin Invest 2001; 31:907-14. PubMed
  • Kontrogianni-Konstantopoulos A, Huang SC, Benz EJ. A nonerythroid isoform of protein 4.1R interacts with components of the contractile apparatus in skeletal myofibers. Mol Biol Cell 2000; 11:3805-17. PubMed
  • Mattagajasingh SN, Huang SC, Hartenstein JS, Benz EJ. Characterization of the interaction between protein 4.1R and ZO-2. A possible link between the tight junction and the actin cytoskeleton. J Biol Chem 2000; 275:30573-85. PubMed
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