My long-term goals are to (1) understand how transcription factors determine cell differentiation and (2) apply this knowledge to treat human diseases.
The transcription factor E47 is critical for early B cell differentiation and proliferation/survival but is dispensable for other cell lineages; thus E47 represents a potential target for treatment of acute B cell leukemia, a neoplastic proliferation of early B cells. To suppress E47 activity, I have engineered a novel dominant-negative E47 that is inducible by tamoxifen. This construct has been subcloned in a lentiviral vector that allows efficient expression in hemopoietic precursors resulting in suppression of E47 activity and suppression of leukemic B cell growth. Using this system, I will determine how suppressing E47 decreases B cell growth, both normal and neoplastic, and identify down-stream target genes of E47. To determine the potential side effect of targeting E47, I will determine the effects of suppressing E47 on non-B cell hematopoiesis.
E47 promotes B cell differentiation by activating B cell-specific genes, a remarkable process since inactive genes are packaged in a chromatin structure that is presumably inaccessible to transcription factors. In fact, E47 can activate B cell specific genes in non-B cells, a feat that cannot be duplicated by another transcription factor, E2-2, even though both factors bind the same DNA site and have strong sequence homology.
Hence, despite the similarities, E47 contains protein domains functionally different from E2-2. To identify protein domains of E47 that can activate chromatin embedded genes, I will swap portions of E47 with equivalent domains of E2-2, express these chimeric constructs in non-B cells, and measure activation by detecting change in chromatin structure and presence of B cell specific transcripts.
- Assistant Professor of Pathology and Laboratory Medicine at the Children's Hospital of Philadelphia (2004 – 2007)
- Assistant Professor of Pathology and Laboratory Medicine at University of Pennsylvania School of Medicine (1998 – 2004)
- Associate Professor of Pathology and Laboratory Medicine at the Children's Hospital of Philadelphia (2007 – 2011)
- Ph.D., Biochemistry, University of Pennsylvania (1991)
- M.D., University of Pennsylvania School of Medicine (1991)
- B.S., Biochemistry, Cornell University (1982)
- Shaffer, M. H. Huang, Y. Corbo, E. Wu, G. F. Velez, M. Choi, J. K. Saotome, I. Cannon, J. L. McClatchey, A. I. Sperling, A. I. Maltzman, J. S. Oliver, P. M. Bhandoola, A. Laufer, T. M. Burkhardt, J. K.. Ezrin is highly expressed in early thymocytes, but dispensable for T cell development in mice. PLoS One. Vol 5(8) . 2010 August:e12404.
- Yu, D. dos Santos, C. O. Zhao, G. Jiang, J. Amigo, J. D. Khandros, E. Dore, L. C. Yao, Y. D'Souza, J. Zhang, Z. Ghaffari, S. Choi, J. Friend, S. Tong, W. Orange, J. S. Paw, B. H. Weiss, M. J.. miR-451 protects against erythroid oxidant stress by repressing 14-3-3zeta. Genes Dev. Vol 24(15) . 2010 August:1620-33.
- Miccio A, Wang Y, Hong W, Gregory GD, Wang H, Yu X, Choi JK, Shelat S, Tong W, Poncz M, Blobel GA.. NuRD mediates activating and repressive functions of GATA-1 and FOG-1 during blood development. EMBO J. 2010 Jan.
- Talaat, K. R. Rothman, J. A. Cohen, J. I. Santi, M. Choi, J. K. Guzman, M. Zimmerman, R. Nallasamy, S. Brucker, A. Quezado, M. Pittaluga, S. Patronas, N. J. Klion, A. D. Nichols, K. E.. Lymphocytic vasculitis involving the central nervous system occurs in patients with X-linked lymphoproliferative disease in the absence of Epstein-Barr virus infection. Pediatr Blood Cancer. Vol 53(6) . 2009 December:1120-3.
- Sanchez PV, Perry RL, Sarry JE, Perl AE, Murphy K, Swider CR, Bagg A, Choi JK, Biegel JA, Danet-Desnoyers G, Carroll M. A robust xenotransplantation model for acute myeloid leukemia. Leukemia. Vol 23(11) . 2009 November:2109-17.
- Diana A. Corao, Jaclyn A. Biegel, Cheryl M. Coffin, Frederic G. Barr, Luanne M. Wainwright, Linda M. Ernst, John K. Choi, Paul J. Zhang, Bruce R. Pawel.. ALK Expression in Rhabdomyosarcomas: Correlation with Histologic Subtype and Fusion Status.. Pediatric and Developmental Pathology. Vol 12(4) . 2009 July:275-83.
- Michele Roullet, MD, Shereen MF Gheith MBBCH, MSC, PhD, Joanne Mauger, Jacqueline M. Junkins-Hopkins MD, and John K Choi MD, PhD.. Percentage of Gamma/Delta T Cells in Panniculitis by Paraffin Immunohistochemistry. AJCP. Vol 131. 2009 June:820-826.
- David T. Teachey, Robert Greiner, Alix Seif, Edward Attiyeh, Jack Bleesing, John Choi, Catherine Manno, Eric Rappaport, Dirk Schwabe, Cecilia Sheen, Katherine Sullivan, Homing Zhuang, Daniel Wechsler, and Stephan A. Grupp. Treatment with sirolimus results in complete responses in patients with Autoimmune Lymphoproliferative Syndrome. Brit J Hematol. Vol 145(1) . 2009 April:101-6.
- Lurong Lian, Yanfeng Wang, Matthew Flick, John Choi, Edward W. Scott, Jay Degen, Mark A. Lemmon, and Charles S. Abrams.. Loss of pleckstrin defines a novel pathway for PKC-mediated exocytosis.. Blood. Vol 113(15) . 2009 April:3577-84.
- Stella T. Chou, Joanna B. Opalinska, Yu Yao, Myriam Fernandez, Anna Kalota, John S.J. Brooks, John K. Choi, Alan Gewirtz, Gwenn-ael Danet-Desnoyers, Richard L. Nemiroff, Mitchell J. Weiss.. Trisomy 21 enhances human fetal erythro-megakaryocytic development.. Blood. Vol 112(12) . 2008 Dec:4503-6.