Photo of Edward J. Benz,   MD

Edward J. Benz, MD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-2015
Fax: (617) 632-2161


edward_benz@dfci.harvard.edu

Photo of Edward J. Benz,   MD

Dana-Farber Cancer Institute
Phone: (617) 632-2015
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 and CEO Emeritus, Office of the President, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

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 from Harvard Catalyst Profiles

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  • Schilsky RL, Nass S, Le Beau MM, Benz EJ. Progress in Cancer Research, Prevention, and Care. N Engl J Med 2020; 383:897-900. PubMed
  • Shulman LN, Sheldon LK, Benz EJ. The Future of Cancer Care in the United States-Overcoming Workforce Capacity Limitations. JAMA Oncol 2020. PubMed
  • Huang SC, Liang JY, Vu LV, Yu FH, Ou AC, Ou JP, Zhang HS, Burnett KM, Benz EJ. Epithelial-specific isoforms of protein 4.1R promote adherens junction assembly in maturing epithelia. J Biol Chem 2019. PubMed
  • Benz EJ, Mondoro TH, Gibbons GH. Accelerating the Science of SCD Therapies-Is a Cure Possible? JAMA 2019. PubMed
  • Huang SC, Zhang HS, Yu B, McMahon E, Nguyen DT, Yu FH, Ou AC, Park Ou J, Benz EJ. Protein 4.1R exon 16 3' splice site activation requires coordination among TIA1, Pcbp1, and RBM39 during terminal erythropoiesis. Mol Cell Biol 2017. PubMed
  • Huang SC, Zhou A, Nguyen DT, Zhang HS, Benz EJ. Protein 4.1R Influences Myogenin Protein Stability and Skeletal Muscle Differentiation. J Biol Chem 2016; 291:25591-25607. PubMed
  • Nardi EA, Wolfson JA, Rosen ST, Diasio RB, Gerson SL, Parker BA, Alvarnas JC, Levine HA, Fong Y, Weisenburger DD, Fitzgerald CL, Egan M, Stranford S, Carlson RW, Benz EJ. Value, Access, and Cost of Cancer Care Delivery at Academic Cancer Centers. J Natl Compr Canc Netw 2016; 14:837-47. PubMed
  • Tefferi A, Kantarjian H, Rajkumar SV, Baker LH, Abkowitz JL, Adamson JW, Advani RH, Allison J, Antman KH, Bast RC, Bennett JM, Benz EJ, Berliner N, Bertino J, Bhatia R, Bhatia S, Bhojwani D, Blanke CD, Bloomfield CD, Bosserman L, Broxmeyer HE, Byrd JC, Cabanillas F, Canellos GP, Chabner BA, Chanan-Khan A, Cheson B, Clarkson B, Cohn SL, Colon-Otero G, Cortes J, Coutre S, Cristofanilli M, Curran WJ, Daley GQ, DeAngelo DJ, Deeg HJ, Einhorn LH, Erba HP, Esteva FJ, Estey E, Fidler IJ, Foran J, Forman S, Freireich E, Fuchs C, George JN, Gertz MA, Giralt S, Golomb H, Greenberg P, Gutterman J, Handin RI, Hellman S, Hoff PM, Hoffman R, Hong WK, Horowitz M, Hortobagyi GN, Hudis C, Issa JP, Johnson BE, Kantoff PW, Kaushansky K, Khayat D, Khuri FR, Kipps TJ, Kripke M, Kyle RA, Larson RA, Lawrence TS, Levine R, Link MP, Lippman SM, Lonial S, Lyman GH, Markman M, Mendelsohn J, Meropol NJ, Messinger Y, Mulvey TM, O'Brien S, Perez-Soler R, Pollock R, Prchal J, Press O, Radich J, Rai K, Rosenberg SA, Rowe JM, Rugo H, Runowicz CD, Sandmaier BM, Saven A, Schafer AI, Schiffer C, Sekeres MA, Silver RT, Siu LL, Steensma DP, Stewart FM, Stock W, Stone R, Storb R, Strong LC, Tallman MS, Thompson M, Ueno NT, Van Etten RA, Vose JM, Wiernik PH, Winer EP, Younes A, Zelenetz AD, LeMaistre CA. In Support of a Patient-Driven Initiative and Petition to Lower the High Price of Cancer Drugs. Mayo Clin. Proc. 2015; 90:996-1000. PubMed
  • 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 2008; 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
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