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:

Acute tissue injury activates satellite cells and promotes sarcoma formation via the HGF/c-MET signaling pathway.

Some patients with soft-tissue sarcoma (STS) report a history of injury at the site of their tumor. Although this phenomenon is widely reported, there are relatively few experimental systems that have directly assessed the role of injury in sarcoma formation. We recently described a mouse model of STS whereby p53 is deleted and oncogenic Kras is activated in muscle satellite cells via a Pax7(CreER) driver following intraperitoneal injection with tamoxifen. Here, we report that after systemic injection of tamoxifen, the vast majority of Pax7-expressing cells remain quiescent despite mutation of p53 and Kras. The fate of these muscle progenitors is dramatically altered by tissue injury, which leads to faster kinetics of sarcoma formation. In adult muscle, quiescent satellite cells will transition into an active state in response to hepatocyte growth factor (HGF). We show that modulating satellite cell quiescence via intramuscular injection of HGF increases the penetrance of sarcoma formation at the site of injection, which is dependent on its cognate receptor c-MET. Unexpectedly, the tumor-promoting effect of tissue injury also requires c-Met. These results reveal a mechanism by which HGF/c-MET signaling promotes tumor formation after tissue injury in a mouse model of primary STS, and they may explain why some patients develop a STS at the site of injury.
Authors
Van Mater, D; Añó, L; Blum, JM; Webster, MT; Huang, W; Williams, N; Ma, Y; Cardona, DM; Fan, C-M; Kirsch, DG
MLA Citation
Van Mater, David, et al. “Acute tissue injury activates satellite cells and promotes sarcoma formation via the HGF/c-MET signaling pathway..” Cancer Res, vol. 75, no. 3, Feb. 2015, pp. 605–14. Pubmed, doi:10.1158/0008-5472.CAN-14-2527.
URI
https://scholars.duke.edu/individual/pub1054203
PMID
25503558
Source
pubmed
Published In
Cancer Res
Volume
75
Published Date
Start Page
605
End Page
614
DOI
10.1158/0008-5472.CAN-14-2527

Transient activation of beta -catenin signaling in cutaneous keratinocytes is sufficient to trigger the active growth phase of the hair cycle in mice.

Wnts have key roles in many developmental processes, including hair follicle growth and differentiation. Stabilization of beta-catenin is essential in the canonical Wnt signaling pathway. We developed transgenic mice expressing a regulated form of beta-catenin in the skin. Chronic activation of beta-catenin in resting (telogen) hair follicles resulted in changes consistent with induction of an exaggerated, aberrant growth phase (anagen). Transient activation of beta-catenin produced a normal anagen. Our data lend strong support to the notion that a Wnt/beta-catenin signal operating on hair follicle precursor cells serves as a crucial proximal signal for the telogen-anagen transition.
Authors
Van Mater, D; Kolligs, FT; Dlugosz, AA; Fearon, ER
MLA Citation
Van Mater, David, et al. “Transient activation of beta -catenin signaling in cutaneous keratinocytes is sufficient to trigger the active growth phase of the hair cycle in mice..” Genes Dev, vol. 17, no. 10, May 2003, pp. 1219–24. Pubmed, doi:10.1101/gad.1076103.
URI
https://scholars.duke.edu/individual/pub1114003
PMID
12756226
Source
pubmed
Published In
Genes & Development
Volume
17
Published Date
Start Page
1219
End Page
1224
DOI
10.1101/gad.1076103

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

Methods to generate genetically engineered mouse models of soft tissue sarcoma.

We discuss the generation of primary soft tissue sarcomas in mice using the Cre-loxP system to activate conditional mutations in oncogenic Kras and the tumor suppressor p53 (LSL-Kras(G12D/+); p53(flox/flox)). Sarcomas can be generated either by adenoviral delivery of Cre recombinase, activation of transgenic Cre recombinase with tamoxifen, or through transplantation of isolated satellite cells with Cre activation in vitro. Various applications of these models are discussed, including anticancer therapies, metastasis, in vivo imaging, and genetic requirements for tumorigenesis.
Authors
Dodd, RD; Añó, L; Blum, JM; Li, Z; Van Mater, D; Kirsch, DG
MLA Citation
Dodd, Rebecca D., et al. “Methods to generate genetically engineered mouse models of soft tissue sarcoma..” Methods Mol Biol, vol. 1267, 2015, pp. 283–95. Pubmed, doi:10.1007/978-1-4939-2297-0_13.
URI
https://scholars.duke.edu/individual/pub1057458
PMID
25636474
Source
pubmed
Published In
Methods Mol Biol
Volume
1267
Published Date
Start Page
283
End Page
295
DOI
10.1007/978-1-4939-2297-0_13

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

Research Areas:

Neurofibromatosis
Neurofibromatosis 1
Neurofibromatosis 2
Neurofibromatosis in children
Sarcoma