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:

Dissecting the role of injury is sarcoma formation

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

Dissecting the role of injury is sarcoma formation

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

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

Publications:

Bone marrow transplantation for CVID-like humoral immune deficiency associated with red cell aplasia.

Patients with common variable immunodeficiency (CVID) have a higher incidence of autoimmune disease, which may mark the disease onset; however, anemia secondary to pure red cell aplasia is an uncommon presenting feature. Here, we describe a case of CVID-like humoral immune deficiency in a child who initially presented with red cell aplasia and ultimately developed progressive bone marrow failure. Although bone marrow transplantation (BMT) has been associated with high mortality in CVID, our patient was successfully treated with a matched sibling BMT and engrafted with >98% donor chimerism and the development of normal antibody titers to diphtheria and tetanus toxoids.
Authors
Sayour, EJ; Mousallem, T; Van Mater, D; Wang, E; Martin, P; Buckley, RH; Barfield, RC
MLA Citation
Sayour, Elias J., et al. “Bone marrow transplantation for CVID-like humoral immune deficiency associated with red cell aplasia..” Pediatr Blood Cancer, vol. 63, no. 10, Oct. 2016, pp. 1856–59. Pubmed, doi:10.1002/pbc.26092.
URI
https://scholars.duke.edu/individual/pub1133982
PMID
27273469
Source
pubmed
Published In
Pediatr Blood Cancer
Volume
63
Published Date
Start Page
1856
End Page
1859
DOI
10.1002/pbc.26092

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

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

MicroRNA-182 drives metastasis of primary sarcomas by targeting multiple genes.

Metastasis causes most cancer deaths, but is incompletely understood. MicroRNAs can regulate metastasis, but it is not known whether a single miRNA can regulate metastasis in primary cancer models in vivo. We compared the expression of miRNAs in metastatic and nonmetastatic primary mouse sarcomas and found that microRNA-182 (miR-182) was markedly overexpressed in some tumors that metastasized to the lungs. By utilizing genetically engineered mice with either deletion of or overexpression of miR-182 in primary sarcomas, we discovered that deletion of miR-182 substantially decreased, while overexpression of miR-182 considerably increased, the rate of lung metastasis after amputation of the tumor-bearing limb. Additionally, deletion of miR-182 decreased circulating tumor cells (CTCs), while overexpression of miR-182 increased CTCs, suggesting that miR-182 regulates intravasation of cancer cells into the circulation. We identified 4 miR-182 targets that inhibit either the migration of tumor cells or the degradation of the extracellular matrix. Notably, restoration of any of these targets in isolation did not alter the metastatic potential of sarcoma cells injected orthotopically, but the simultaneous restoration of all 4 targets together substantially decreased the number of metastases. These results demonstrate that a single miRNA can regulate metastasis of primary tumors in vivo by coordinated regulation of multiple genes.
Authors
Sachdeva, M; Mito, JK; Lee, C-L; Zhang, M; Li, Z; Dodd, RD; Cason, D; Luo, L; Ma, Y; Van Mater, D; Gladdy, R; Lev, DC; Cardona, DM; Kirsch, DG
MLA Citation
Sachdeva, Mohit, et al. “MicroRNA-182 drives metastasis of primary sarcomas by targeting multiple genes..” J Clin Invest, vol. 124, no. 10, Oct. 2014, pp. 4305–19. Pubmed, doi:10.1172/JCI77116.
URI
https://scholars.duke.edu/individual/pub1048133
PMID
25180607
Source
pubmed
Published In
J Clin Invest
Volume
124
Published Date
Start Page
4305
End Page
4319
DOI
10.1172/JCI77116

Distinct and overlapping sarcoma subtypes initiated from muscle stem and progenitor cells.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, whereas undifferentiated pleomorphic sarcoma (UPS) is one of the most common soft tissue sarcomas diagnosed in adults. To investigate the myogenic cell(s) of origin of these sarcomas, we used Pax7-CreER and MyoD-CreER mice to transform Pax7(+) and MyoD(+) myogenic progenitors by expressing oncogenic Kras(G12D) and deleting Trp53 in vivo. Pax7-CreER mice developed RMS and UPS, whereas MyoD-CreER mice developed UPS. Using gene set enrichment analysis, RMS and UPS each clustered specifically within their human counterparts. These results suggest that RMS and UPS have distinct and overlapping cells of origin within the muscle lineage. Taking them together, we have established mouse models of soft tissue sarcoma from muscle stem and progenitor cells.
Authors
Blum, JM; Añó, L; Li, Z; Van Mater, D; Bennett, BD; Sachdeva, M; Lagutina, I; Zhang, M; Mito, JK; Dodd, LG; Cardona, DM; Dodd, RD; Williams, N; Ma, Y; Lepper, C; Linardic, CM; Mukherjee, S; Grosveld, GC; Fan, C-M; Kirsch, DG
MLA Citation
Blum, Jordan M., et al. “Distinct and overlapping sarcoma subtypes initiated from muscle stem and progenitor cells..” Cell Rep, vol. 5, no. 4, Nov. 2013, pp. 933–40. Pubmed, doi:10.1016/j.celrep.2013.10.020.
URI
https://scholars.duke.edu/individual/pub1000373
PMID
24239359
Source
pubmed
Published In
Cell Reports
Volume
5
Published Date
Start Page
933
End Page
940
DOI
10.1016/j.celrep.2013.10.020

Research Areas:

Neurofibromatosis
Neurofibromatosis 1
Neurofibromatosis 2
Neurofibromatosis in children
Sarcoma