Division Chief, Pediatric Hematology-Oncology

Department / Division:
Pediatrics / Hematology-Oncology

Address:
DUMC 102382
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:
Our laboratory has two major research interests:

1)We are currently investigating the role of MLL-CALM, a novel hybrid protein first identified in the leukemic blasts of an infant with acute myeloid leukemia (AML), in  myeloid leukemogenesis.  Expression of MLL-CALM disrupts endocytosis and intracellular vesicle transport, processes involved in regulation of growth factor signaling.  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.  We have also recently determined that CALM plays a previously unrecognized role in transcriptional regulation, and we are in the process of defining the importance of the CALM transcriptional activation domain in leukemogenesis.  A better understanding of CALM's function in normal and malignant hematopoiesis 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:
Teachey DT, Greiner R, Seif A, Attiyeh E, Bleesing J, Choi J, Manno C, Rappaport E, Schwabe D, Sheen C, Sullivan KE, Zhuang H, Wechsler DS, Grupp SA. Treatment with sirolimus results in complete responses in patients with autoimmune lymphoproliferative syndrome. Br J Haematol. 2009 Apr;145(1):101-6. (2009) Abstract

Hastings C, Wechsler DS, Stine KC, Graham DK, Abshire T. Consensus on a core curriculum in American training programs in pediatric hematology-oncology: a report from the ASPHO Training Committee. Pediatr Hematol Oncol. 2007 Oct-Nov;24(7):503-12. (2007) Abstract

Khare RK, Settimi PD, Mba NI, Wechsler DS, Bratton SL, Williams DM. Aortobronchial fistula in a pediatric patient with massive hemoptysis: treatment by means of an aortic endograft. Ann Thorac Surg. 2005 Aug;80(2):731-3. (2005) Abstract

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

Mody RJ, Brown PI, Wechsler DS. Refractory iron deficiency anemia as the primary clinical manifestation of celiac disease. J Pediatr Hematol Oncol. 2003 Feb;25(2):169-72. (2003) Abstract

Snyder KM, Rubin MA, Shulkin BL, Hutchinson RJ, Wechsler DS. Mediastinal seminoma in a patient with Wiskott-Aldrich syndrome. J Pediatr Hematol Oncol. 2002 Nov;24(8):672-6. (2002) 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, Papoulas O, Dang CV, Kingston RE. Differential binding of c-Myc and Max to nucleosomal DNA. Mol Cell Biol. 1994 Jun;14(6):4097-107. (1994) 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

Bova GS, Wechsler DS, Van Dang C, Isaacs WB. TaqI polymorphism of the human MXI1 gene. Hum Mol Genet. 1994 Dec;3(12):2266. (1994) Abstract