David Van Mater

Overview:

I am a pediatric oncologist with a specific interest in hereditary cancer syndromes and sarcoma. I also director of the Duke Comprehensive Neurofibromatosis Clinic where I see children and adults with neurofibromatosis type I and II, in addition to schwannomatosis. 

Positions:

Assistant Professor of Pediatrics

Pediatrics, Hematology-Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

MD./PhD. 2006

University of Michigan at Ann Arbor

Pediatrics Internship and Residency, Pediatrics

University of Michigan at Ann Arbor

Pediatric Hematology/Oncology Fellowship, Pediatrics

Duke University School of Medicine

Grants:

PBTC-042 (Phase 1 of PD-0332991)

Administered By
Pediatrics, Hematology-Oncology
Role
Principal Investigator
Start Date
End Date

NF1-OPG

Administered By
Pediatrics, Hematology-Oncology
Role
Principal Investigator
Start Date
End Date

Visual Field Outcomes in Pediatric Patients with NF1-associated Optic Pathway Gliomas

Administered By
Pediatrics, Hematology-Oncology
Role
Principal Investigator
Start Date
End Date

Expansion of the AYA Oncology Initiative at Duke University

Administered By
Pediatrics, Hematology-Oncology
Role
Principal Investigator
Start Date
End Date

Publications:

Mutational landscape in genetically engineered, carcinogen-induced, and radiation-induced mouse sarcoma.

Cancer development is influenced by hereditary mutations, somatic mutations due to random errors in DNA replication, or external factors. It remains unclear how distinct cell-intrinsic and -extrinsic factors impact oncogenesis within the same tissue type. We investigated murine soft tissue sarcomas generated by oncogenic alterations (KrasG12D activation and p53 deletion), carcinogens (3-methylcholanthrene [MCA] or ionizing radiation), and in a novel model combining both factors (MCA plus p53 deletion). Whole-exome sequencing demonstrated distinct mutational signatures in individual sarcoma cohorts. MCA-induced sarcomas exhibited high mutational burden and predominantly G-to-T transversions, while radiation-induced sarcomas exhibited low mutational burden and a distinct genetic signature characterized by C-to-T transitions. The indel to substitution ratio and amount of gene copy number variations were high for radiation-induced sarcomas. MCA-induced tumors generated on a p53-deficient background showed the highest genomic instability. MCA-induced sarcomas harbored mutations in putative cancer-driver genes that regulate MAPK signaling (Kras and Nf1) and the Hippo pathway (Fat1 and Fat4). In contrast, radiation-induced sarcomas and KrasG12Dp53-/- sarcomas did not harbor recurrent oncogenic mutations, rather they exhibited amplifications of specific oncogenes: Kras and Myc in KrasG12Dp53-/- sarcomas, and Met and Yap1 for radiation-induced sarcomas. These results reveal that different initiating events drive oncogenesis through distinct mechanisms.
Authors
Lee, C-L; Mowery, YM; Daniel, AR; Zhang, D; Sibley, AB; Delaney, JR; Wisdom, AJ; Qin, X; Wang, X; Caraballo, I; Gresham, J; Luo, L; Van Mater, D; Owzar, K; Kirsch, DG
MLA Citation
Lee, Chang-Lung, et al. “Mutational landscape in genetically engineered, carcinogen-induced, and radiation-induced mouse sarcoma..” Jci Insight, vol. 4, no. 13, July 2019. Pubmed, doi:10.1172/jci.insight.128698.
URI
https://scholars.duke.edu/individual/pub1385855
PMID
31112524
Source
pubmed
Published In
Jci Insight
Volume
4
Published Date
DOI
10.1172/jci.insight.128698

ITF-2, a downstream target of the Wnt/TCF pathway, is activated in human cancers with beta-catenin defects and promotes neoplastic transformation.

In many cancers, inactivation of the adenomatous polyposis coli (APC) or Axin tumor suppressor proteins or activating mutations in beta-catenin lead to elevated beta-catenin levels, enhanced binding of beta-catenin to T cell factor (TCF) proteins, and increased expression of TCF-regulated genes. We found that the gene for the basic helix-loop-helix transcription factor ITF-2 (immunoglobulin transcription factor-2) was activated in rat E1A-immortalized RK3E cells following neoplastic transformation by beta-catenin or ligand-induced activation of a beta-catenin-estrogen receptor fusion protein. Human cancers with beta-catenin regulatory defects had elevated ITF-2 expression, and ITF-2 was repressed by restoring wild-type APC function or inhibiting TCF activity. Of note, ITF-2 promoted neoplastic transformation of RK3E cells. We propose that ITF-2 is a TCF-regulated gene, which functions in concert with other TCF target genes to promote growth and/or survival of cancer cells with defects in beta-catenin regulation.
Authors
Kolligs, FT; Nieman, MT; Winer, I; Hu, G; Van Mater, D; Feng, Y; Smith, IM; Wu, R; Zhai, Y; Cho, KR; Fearon, ER
MLA Citation
Kolligs, Frank T., et al. “ITF-2, a downstream target of the Wnt/TCF pathway, is activated in human cancers with beta-catenin defects and promotes neoplastic transformation..” Cancer Cell, vol. 1, no. 2, Mar. 2002, pp. 145–55. Pubmed, doi:10.1016/s1535-6108(02)00035-1.
URI
https://scholars.duke.edu/individual/pub1114004
PMID
12086873
Source
pubmed
Published In
Cancer Cell
Volume
1
Published Date
Start Page
145
End Page
155
DOI
10.1016/s1535-6108(02)00035-1

Favorable response to nivolumab in a young adult patient with metastatic histiocytic sarcoma.

Authors
Bose, S; Robles, J; McCall, CM; Lagoo, AS; Wechsler, DS; Schooler, GR; Van Mater, D
MLA Citation
Bose, Shree, et al. “Favorable response to nivolumab in a young adult patient with metastatic histiocytic sarcoma..” Pediatr Blood Cancer, vol. 66, no. 1, Jan. 2019. Pubmed, doi:10.1002/pbc.27491.
URI
https://scholars.duke.edu/individual/pub1353430
PMID
30270506
Source
pubmed
Published In
Pediatr Blood Cancer
Volume
66
Published Date
Start Page
e27491
DOI
10.1002/pbc.27491

Growth hormone regulates phosphorylation and function of CCAAT/enhancer-binding protein beta by modulating Akt and glycogen synthase kinase-3.

Growth hormone (GH) regulates transcription factors associated with c-fos, including C/EBPbeta. Two forms of C/EBPbeta, liver-activating protein (LAP) and liver inhibitory protein (LIP), are dephosphorylated in GH-treated 3T3-F442A fibroblasts. GH-induced dephosphorylation of LAP and LIP is reduced when cells are preincubated with phosphatidylinositol 3'-kinase (PI3K) inhibitors. GH activates Akt and inhibits glycogen synthase kinase-3 (GSK-3). Lithium, a GSK-3 inhibitor, increases GH-dependent dephosphorylation of LAP and LIP. Both are in vitro substrates of GSK-3, suggesting that GSK-3 inactivation contributes to GH-promoted dephosphorylation of C/EBPbeta. Alkaline phosphatase increases binding of LAP homodimers and decreases binding of LIP homodimers to c-fos, suggesting that dephosphorylation of C/EBPbeta modifies their ability to bind DNA. Both alkaline phosphatase- and GH-mediated dephosphorylation comparably increase binding of endogenous LAP in 3T3-F442A cells. In cells overexpressing LAP and GSK-3, LAP binding decreases, suggesting that GSK-3-mediated phosphorylation interferes with LAP binding. Expression of constitutively active GSK-3 reduced GH-stimulated c-fos promoter activity. These studies indicate that PI3K/Akt/GSK-3 mediates signaling between GH receptor and the nucleus, promoting dephosphorylation of C/EBPbeta. Dephosphorylation increases binding of LAP complexes to the c-fos promoter and may contribute to the participation of C/EBPbeta in GH-stimulated c-fos expression.
Authors
Piwien-Pilipuk, G; Van Mater, D; Ross, SE; MacDougald, OA; Schwartz, J
MLA Citation
Piwien-Pilipuk, G., et al. “Growth hormone regulates phosphorylation and function of CCAAT/enhancer-binding protein beta by modulating Akt and glycogen synthase kinase-3..” J Biol Chem, vol. 276, no. 22, June 2001, pp. 19664–71. Pubmed, doi:10.1074/jbc.M010193200.
URI
https://scholars.duke.edu/individual/pub1114005
PMID
11278638
Source
pubmed
Published In
The Journal of Biological Chemistry
Volume
276
Published Date
Start Page
19664
End Page
19671
DOI
10.1074/jbc.M010193200

Management of recurrent Ewing sarcoma: challenges and approaches.

Although many patients with newly diagnosed Ewing sarcoma can become long-term survivors, relapse remains an important clinical problem for which there is no standard approach. Several prognostic factors have been identified, and these may help guide patient counseling and therapy decisions. A variety of chemotherapy regimens have produced responses in patients with recurrent Ewing sarcoma, but no comparative studies have been completed to show superiority of any one particular approach. In addition, the optimum length of therapy for salvage regimens and use of local control measures remains unknown. The likelihood of cure remains low and the gaps in our knowledge are great, and so enrollment on clinical trials should be strongly encouraged for these patients when feasible. Because Ewing sarcoma is relatively rare, some pediatric and adult oncologists may be less familiar with the management of relapsed patients. In this review, we address common questions facing the clinician and patient, and provide an update on new strategies for therapy.
MLA Citation
Van Mater, David, and Lars Wagner. “Management of recurrent Ewing sarcoma: challenges and approaches..” Onco Targets Ther, vol. 12, 2019, pp. 2279–88. Pubmed, doi:10.2147/OTT.S170585.
URI
https://scholars.duke.edu/individual/pub1381184
PMID
30988632
Source
pubmed
Published In
Oncotargets and Therapy
Volume
12
Published Date
Start Page
2279
End Page
2288
DOI
10.2147/OTT.S170585

Research Areas:

Neurofibromatosis
Neurofibromatosis 1
Neurofibromatosis 2
Neurofibromatosis in children
Sarcoma