Department / Division:
Pediatrics / Hematology-Oncology

Address:
DUMC 2916
Durham, NC 27710

Appointment Telephone:
919-668-4000

Office Telephone:
919-684-3401

Fax Telephone:
919-681-7950

• MD, CM, McGill University Faculty of Medicine (Canada), 1987
• PhD, Physiology, McGill University (Canada), 1987

• Pediatrics, Johns Hopkins Hospital (Maryland), 1987-1990

• Pediatric Hematology-Oncology, Johns Hopkins Hospital (Maryland), 1990-1994

Clinical Interests:
Pediatric leukemias and lymphomas, neuroblastoma, histiocytosis

Research Interests:
My laboratory has two major research interests:

1)We have been investigating how MLL-CALM, a novel hybrid protein first identified in the leukemic blasts of an infant acute myeloid leukemia (AML), contributes to myeloid leukemogenesis.  Expression of MLL-CALM disrupts endocytosis, the process by which cells internalize growth factor signals.  The lab is actively involved in understanding which domains of CALM contribute to perturbation of endocytosis, and whether restored endocytosis results in decreased leukemogenesis. These studies are carried out both in vitro and in vivo, taking advantage of CALM-deficient fit1 mice.  The lab has also determined that CALM plays a previously unrecognized role in transcriptional regulation and is in the process of defining these specific domains.  A better understanding of how disrupted endocytosis gives rise to leukemia also has implications for the pathogenesis of other malignancies.

2)In addition, our lab is continuing to address the function of Mxi1, a Myc antagonist, in the pathogenesis of neuroblastoma, the most common extracranial solid tumor of childhood.  We have recently been focused on a novel role for Mxi0, an alternatively transcribed Mxi1 isoform that appears to lack the transcriptional repression properties of Mxi1.  Expression of MXI0 appears to correlate with that of MYCN, suggesting coordinate regulation.  The identification of MXI0 deepens the complexity of regulation by MYC family members in neuroblastoma, and raises the possibility of novel therapeutic interventions for these difficult to treat tumors.

Representative Publications:
Choi SW, Wechsler DS. Burkitt lymphoma in a child with osteogenesis imperfecta. Pediatr Blood Cancer. 2005 Nov;45(6):863-4. (2005) Abstract

Chao MM, Schwartz JL, Wechsler DS, Thornburg CD, Griffith KA, Williams JA. High-risk surgically resected pediatric melanoma and adjuvant interferon therapy. Pediatr Blood Cancer. 2005 May;44(5):441-8. (2005) Abstract

Armstrong MB, Nafiu OO, Valdez R, Park JM, Williams JA, Wechsler DS. Testicular chloroma in a nonleukemic infant. J Pediatr Hematol Oncol. 2005 Jul;27(7):393-6. (2005) Abstract

Lau JJ, Trobe JD, Ruiz RE, Cho RW, Wechsler DS, Shah GV, Gebarski SS. Metastatic neuroblastoma presenting with binocular blindness from intracranial compression of the optic nerves. J Neuroophthalmol. 2004 Jun;24(2):119-24. (2004) Abstract

Engstrom LD, Youkilis AS, Gorelick JL, Zheng D, Ackley V, Petroff CA, Benson LQ, Coon MR, Zhu X, Hanash SM, Wechsler DS. Mxi1-0, an alternatively transcribed Mxi1 isoform, is overexpressed in glioblastomas. Neoplasia. 2004 Sep-Oct;6(5):660-73. (2004) Abstract

van den Boom J, Wolter M, Kuick R, Misek DE, Youkilis AS, Wechsler DS, Sommer C, Reifenberger G, Hanash SM. Characterization of gene expression profiles associated with glioma progression using oligonucleotide-based microarray analysis and real-time reverse transcription-polymerase chain reaction. Am J Pathol. 2003 Sep;163(3):1033-43. (2003) Abstract

Wechsler DS, Engstrom LD, Alexander BM, Motto DG, Roulston D. A novel chromosomal inversion at 11q23 in infant acute myeloid leukemia fuses MLL to CALM, a gene that encodes a clathrin assembly protein. Genes Chromosomes Cancer. 2003 Jan;36(1):26-36. (2003) Abstract

Taj MM, Tawil RJ, Engstrom LD, Zeng Z, Hwang C, Sanda MG, Wechsler DS. Mxi1, a Myc antagonist, suppresses proliferation of DU145 human prostate cells. Prostate. 2001 May 15;47(3):194-204. (2001) Abstract

Benson LQ, Coon MR, Krueger LM, Han GC, Sarnaik AA, Wechsler DS. Expression of MXI1, a Myc antagonist, is regulated by Sp1 and AP2. J Biol Chem. 1999 Oct 1;274(40):28794-802. (1999) Abstract

Wechsler DS, Shelly CA, Petroff CA, Dang CV. MXI1, a putative tumor suppressor gene, suppresses growth of human glioblastoma cells. Cancer Res. 1997 Nov 1;57(21):4905-12. (1997) Abstract

Wechsler DS, Shelly CA, Dang CV. Genomic organization of human MXI1, a putative tumor suppressor gene. Genomics. 1996 Mar 15;32(3):466-70. (1996) Abstract

Wechsler DS, Hawkins AL, Li X, Jabs EW, Griffin CA, Dang CV. Localization of the human Mxi1 transcription factor gene (MXI1) to chromosome 10q24-q25. Genomics. 1994 Jun;21(3):669-72. (1994) Abstract