Daniel S. Wechsler, MD, PhD

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Associate Professor of Pediatrics
Associate Professor of Pharmacology & Cancer Biology
Division Chief, Pediatric Hematology-Oncology
Department / Division:
Pediatrics / Pediatrics-Hematology/Oncology
Address:
DUMC 102382
Durham, NC 27710
Appointment Telephone:
919-684-3401
Office Telephone:
919-684-3401
Fax:
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.
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.  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-Oncology (Informa). 2007;24:503-512.  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.  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 & Cancer. 2005;44:441-448.  Abstract
  • Choi, SW; Wechsler, DS. Burkitt lymphoma in a child with osteogenesis imperfecta. Pediatric Blood & Cancer. 2005;45:863-864.  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.  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 (New York, N.Y.). 2004;6:660-673.  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.  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.  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.  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. The American journal of pathology. 2003;163:1033-1043.  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.  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.  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. The Journal of biological chemistry. 1999;274:28794-28802.  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.  Abstract
  • Wechsler, DS; Shelly, CA; Dang, CV. Genomic organization of human MXI1, a putative tumor suppressor gene. Genomics. 1996;32:466-470.  Abstract
  • Bova, GS; Wechsler, DS; Van Dang, C; Isaacs, WB. TaqI polymorphism of the human MXI1 gene. Human Molecular Genetics. 1994;3:2266.  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.  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.  Abstract