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Arthur  Bank
Arthur Bank, M.D.
Division Chief of Hematology
Professor of Medicine


Address: 701 W. 168 St. Room 16-1604 New York NY 10032
Phone: 212-305-4186
Fax: 212-923-2090
E-mail:

bank@cancercenter.columbia.edu

Education and Training:
B.A.  1956, Columbia University
M.D. 1960, Harvard University
Residency 1960-61, Boston City Hospital
Affiliations:
bullet  Department of Hematology
bullet  Stem Cell Consortium
bullet  Medicine
bullet  Genetics & Development
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Training Activities:
bullet  Training Program in Genetics & Development
bullet  Integrated Program in Cellular, Molecular & Biophysical Studies
bullet  MD/PhD Program
Research Summary:
(800 words, max)
Human globin gene regulation and gene therapy
Current Research:
The regulation of human globin gene expression is complex, and mediated by both cis-acting DNA sequences within and surrounding the globin genes, and by trans- acting factors differentially active in fetal and adult hematopoietic cells. Our goal is to understand how this process works and to manipulate it to provide new approaches to the treatment of inherited anemias such as sickle cell disease and beta thalassemia. Recently, we have defined a unique chromatin remodeling complex (PYR complex) that uses the transcription factor, Ikaros, as its DNA binding subunit. PYR complex is present only in adult hematopoietic cells, and deletion of its DNA-binding site between the human fetal and adult globin genes delays switching in transgenic mice. We are also analyzing the structure and function of PYR complex in different hematopoietic cell lineages.

Retroviral and lentiviral gene transfer provides an approach to the potential cure of patients with disorders of human hemoglobin. Efficient gene transfer and high level expression of human beta or gamma globin genes into human hematopoietic stem cells (HSC) could accomplish this goal. We are already using methods to: (1) isolate human HSC; (2) grow these HSC ex vivo;(3) transduce HSC with new genes; and (4) select and enrich for those HSC into which such genes have been transferred. We are trying to optimize this system by constructing new defective retroviruses and lentiviruses, and establishing conditions that permit human HSC from patients to be suitably engineered to express normal amounts of human beta or gamma globin genes, and then re-administering the engineered cells as therapy.
Publications:
(6 max)
1. Lopez, R.A., Schoetz, S., DeAngelis, K., O'Neill, D., and Bank, A. : (2002) Multiiple hematopoietic defects and delayed globin switching in Ikaros-null mice.  Proc. Natl. Acad.Sci  99: 602-607

2. Abonour R, Williams DA, Einhorn L, Hall KM, Chen J, Coffman J, Traycoff CM, Bank A, Kato I, Ward M, Williams SD, Hromas R, Robertson MJ, Smith FO, Woo D, Mills B, Srour EF, and Cornetta K : (2000) Efficient retrovirus-mediated transfer of the multidrug resistance 1 gene into autologous human long-term repopulating hematopoietic stem cells.  Nature Med  6: 652-658

3. O'Neill D, Schoetz SS, Lopez RA, Castle M, Rabinowitz L, Shor E, Krawchuk D, Goll MG, Renz M, Seelig HP, Han S, Seong RH, Park SD, Agalioti T, Munshi N, Thanos D, Erdjument-Bromage H, Tempst P, and Bank A: (2000) An Ikaros-containing chromatin remodeling complex in adult-type erythroid cells.  Mol Cell Biol  20: 7572-7582

4. O'Neill D, Yang J, Erdjument-Bromage H, Bornschlegel K, Tempst K, and Bank A: (1999) Tissue-specific and developmental stage-specific DNA binding by a mammalian SWI/SNF complex associated with human fetal-to-adult globin gene switching.  Proc Natl Acad Sci USA  96: 349-354

5. Ward M, Pioli P, Ayello J, Urzi G, Richardson C, Hesdorffer C, and Bank A: (1999) Retroviral transfer and expression of the human multiple drug resistance gene in peripheral blood progenitor cells.  2: 873-876

6. Ward M, Richardson C, Pioli P, Smith L, Podda S, Goff S, Hesdorffer C, and Bank A: (1994) Transfer and expression of the human multiple drug (MDR) gene in human CD34+ cells.  Blood  84: 1408-1414

URL for lab page:
 

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