Physicians

Division Chief, Pediatric Hematology-Oncology

Departments / Divisions

• Pediatrics / Pediatrics-Hematology/Oncology
• Pharmacology & Cancer Biology

Address
DUMC 102382
Durham, NC 27710

Appointment Telephone
919-684-3401

Office Telephone
919-684-3401

Fax Telephone
919-681-7950

Training

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

Residency

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

Fellowship

• 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.

Industry Relationships and Collaborations (What's this?)

This faculty member (or a member of their immediate family) has a working relationship (i.e. consulting, research, and/or educational services) with the companies listed below. These relations have been reported to the health system leadership and, when appropriate, management plans are in place to address potential conflicts.

• Hyundai Motor America
• Striving For More

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. British Journal of Haematology. 2009;145:101-106. (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. Pediatric Hematology and Oncology. 2007;24:503-512. (2007) Abstract

Armstrong, MB; Nafiu, OO; Valdez, R; Park, JM; Williams, JA; Wechsler, DS. Testicular chloroma in a nonleukemic infant. Journal of Pediatric Hematology/Oncology. 2005;27:393-396. (2005) Abstract

Chao, MM; Schwartz, JL; Wechsler, DS; Thornburg, CD; Griffith, KA; Williams, JA. High-risk surgically resected pediatric melanoma and adjuvant interferon therapy. Pediatric Blood and Cancer. 2005;44:441-448. (2005) Abstract

Choi, SW; Wechsler, DS. Burkitt lymphoma in a child with osteogenesis imperfecta. Pediatric Blood and Cancer. 2005;45:863-864. (2005) 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. Annals of Thoracic Surgery. 2005;80:731-733. (2005) 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;6:660-673. (2004) 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. Journal of Neuro-Ophthalmology. 2004;24:119-124. (2004) Abstract

Mody, RJ; Brown, PI; Wechsler, DS. Refractory iron deficiency anemia as the primary clinical manifestation of celiac disease. Journal of Pediatric Hematology/Oncology. 2003;25:169-172. (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 and Cancer. 2003;36:26-36. (2003) 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. American Journal of Pathology. 2003;163:1033-1043. (2003) Abstract

Snyder, KM; Rubin, MA; Shulkin, BL; Hutchinson, RJ; Wechsler, DS. Mediastinal seminoma in a patient with Wiskott-Aldrich syndrome. Journal of Pediatric Hematology/Oncology. 2002;24:672-676. (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. The Prostate. 2001;47:194-204. (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. Journal of Biological Chemistry. 1999;274:28794-28802. (1999) Abstract

Wechsler, DS; Shelly, CA; Petroff, CA; Dang, CV. MXI1, a putative tumor suppressor gene, suppresses growth of human glioblastoma cells. Cancer Research. 1997;57:4905-4912. (1997) Abstract

Wechsler, DS; Shelly, CA; Dang, CV. Genomic organization of human MXI1, a putative tumor suppressor gene. Genomics. 1996;32:466-470. (1996) Abstract

Bova, GS; Wechsler, DS; Van Dang, C; Isaacs, WB. TaqI polymorphism of the human MXI1 gene. Human Molecular Genetics. 1994;3:2266. (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;21:669-672. (1994) Abstract

Wechsler, DS; Papoulas, O; Dang, CV; Kingston, RE. Differential binding of c-Myc and Max to nucleosomal DNA. Molecular and Cellular Biology. 1994;14:4097-4107. (1994) Abstract