David Van Mater

Overview:

I am a pediatric oncologist with a specific interest in hereditary cancer syndromes and sarcoma. I am 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, Ann Arbor

Pediatrics Internship and Residency, Pediatrics

University of Michigan, 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
Awarded By
Sarcoma Alliance for Research Through Collaboration
Role
Principal Investigator
Start Date
End Date

Dissecting the role of injury is sarcoma formation

Administered By
Pediatrics, Hematology-Oncology
Awarded By
Sarcoma Alliance for Research Through Collaboration
Role
Principal Investigator
Start Date
End Date

Phase I study of PD-0332991 for pediatric patiens with retinoblastoma protein (RB)-positive recurrent or refractory central nervous system (CNS) tumors.

Administered By
Pediatrics, Hematology-Oncology
Awarded By
Pfizer, Inc.
Role
Principal Investigator
Start Date
End Date

MAIN STUDY: Developing Evidence-Based Crieteria for Initiating Treatment fo NF1-OPG.

Administered By
Pediatrics, Hematology-Oncology
Awarded By
Children's Tumor Foundation
Role
Principal Investigator
Start Date
End Date

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

Administered By
Pediatrics, Hematology-Oncology
Awarded By
Boston Children's Hospital
Role
Principal Investigator
Start Date
End Date

Publications:

Abstract A64: A role for injury in sarcomagenesis

<jats:title>Abstract</jats:title> <jats:p>We developed a primary mouse model of embryonal rhabdomyosarcoma and discovered that tissue injury dramatically accelerates sarcoma formation at the site of injury. We were intrigued by this finding as many sarcoma patients anecdotally report a history of trauma prior to sarcoma development. We therefore utilized this mouse model system to explore the mechanism of injury-mediated sarcoma formation. Our preliminary findings suggest that the majority of muscle progenitor cells remain quiescent following mutation of genes with high transformation potential. However, tissue injury “flips a switch”, thereby pushing resting muscle progenitor cells into a proliferative phase. In the setting of a normal mouse, proliferation of muscle cells results in resolution of the injury in a matter of weeks. Conversely, when cells in the vicinity of injury harbor transformative gene mutations, the “switch” does not return to an off-state, and a tumor rapidly develops at the injury site.</jats:p> <jats:p>Our novel mouse model of embryonal rhabdomyosarcoma provides temporospatial control over the deletion of p53 and activation of Kras in muscle progenitor cells. Specifically, Pax7-CreERT2 (P7) mice express a tamoxifen-inducible Cre downstream of the endogenous promoter for the satellite cell transcription factor Pax7. P7 mice were crossed to genetically engineered mice containing a lox-STOP-lox cassette upstream of oncogenic K-rasG12D (K) in addition to 2 floxed p53 alleles (P) to generate P7KP mice. P7KP mice were injected with systemic, intraperitoneal (IP) tamoxifen to mediate Cre-dependent recombination in Pax7-expressing cells. When treated in this manner, sarcomas arise throughout the animal with 100% penetrance with a median onset of 45 days. In contrast, tumor onset is dramatically accelerated when P7KP mice are injured with cardiotoxin, a component of cobra venom that causes myonecrosis. P7KP mice treated with IP tamoxifen along with concurrent intramuscular (IM) cardiotoxin develop sarcomas at the site of injury with a median onset of 15 days. Cardiotoxin was next injected into the gastrocnemius muscle at time points either before, concurrent, or after IP tamoxifen to better define the effect of injury on sarcoma formation. Cardiotoxin promoted highly efficient transformation when administered up to 3 days before and up to 21 days after IP tamoxifen administration. Lineage tracing studies showed no appreciable proliferation of recombined Pax7+ cells in the absence of cardiotoxin, suggesting that sarcoma formation requires factors in addition to loss of p53 and activation of K-ras to cause sarcoma.</jats:p> <jats:p>In order to test the hypothesis that proliferating satellite cells are more prone to sarcoma formation, we treated P7KP mice in the gastrocnemius muscle with hepatocyte growth factor (HGF) along with systemic, IP tamoxifen. HGF has been shown to promote proliferation of resting satellite cells. Interestingly, 12/13 mice treated with IM HGF developed sarcomas at the injection site in a median of 37 days versus 3/12 of mice treated with vehicle control. Current experiments are aimed at dissecting the role of the immune system in the cardiotoxin response.</jats:p> <jats:p>Our experiments support the role of tissue injury acting as a classic promoter in the initiator/promoter model of tumorigenesis. Thus perturbation of the microenvironment has a dramatic effect on sarcoma formation. While the majority of cancer therapeutics are directed against mutations within the tumor, our findings reveal alternative candidates to prevent sarcoma initiation and perhaps maintenance. We anticipate that an understanding of signaling events at the earliest stages of sarcoma formation will provide new drug targets to treat existing tumors and potentially prevent the outgrowth of micrometastases.</jats:p> <jats:p>Citation Format: David Van Mater, Leonor Ano, Jordan Blum, David G. Kirsch. A role for injury in sarcomagenesis. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr A64.</jats:p>
Authors
Mater, DV; Ano, L; Blum, J; Kirsch, DG
MLA Citation
Mater, David Van, et al. “Abstract A64: A role for injury in sarcomagenesis.” Cancer Research, vol. 74, no. 20_Supplement, American Association for Cancer Research (AACR), 2014, pp. A64–A64. Crossref, doi:10.1158/1538-7445.pedcan-a64.
URI
https://scholars.duke.edu/individual/pub1430764
Source
crossref
Published In
Cancer Research
Volume
74
Published Date
Start Page
A64
End Page
A64
DOI
10.1158/1538-7445.pedcan-a64

Eye Swelling and Weight Loss in an 18-year-old Adolescent.

Authors
MLA Citation
Cannon, Laura, et al. “Eye Swelling and Weight Loss in an 18-year-old Adolescent.Pediatr Rev, vol. 43, no. 6, June 2022, pp. 350–52. Pubmed, doi:10.1542/pir.2020-004891.
URI
https://scholars.duke.edu/individual/pub1523815
PMID
35641446
Source
pubmed
Published In
Pediatr Rev
Volume
43
Published Date
Start Page
350
End Page
352
DOI
10.1542/pir.2020-004891

A phase I trial of the CDK 4/6 inhibitor palbociclib in pediatric patients with progressive brain tumors: A Pediatric Brain Tumor Consortium study (PBTC-042).

BACKGROUND: Disruption of cell-cycle regulators is a potential therapeutic target for brain tumors in children and adolescents. The aim of this study was to determine the maximum tolerated dose (MTD) and describe toxicities related to palbociclib, a selective cyclin-dependent kinase 4/6 (CDK4/6) inhibitor in pediatric patients with progressive/refractory brain tumors with intact retinoblastoma protein. METHODS: Palbociclib was administered orally starting at 50 mg/m2 daily for the first 21 days of a 28-day course. Dose escalation was according to the Rolling-6 statistical design in less heavily (stratum I) and heavily pretreated (stratum II) patients, and MTD was determined separately for each group. Pharmacokinetic studies were performed during the first course, and pharmacodynamic studies were conducted to evaluate relationships between drug levels and toxicities. RESULTS: A total of 21 patients were enrolled on stratum I and 14 patients on stratum II. The MTD for both strata was 75 mg/m2 . Palbociclib absorption (mean Tmax between 4.9 and 6.6 h) and elimination (mean half-life between 11.3 and 19.5 h) were assessed. The most common toxicity was myelosuppression. Higher palbociclib exposure was associated with grade 3/4 neutropenia and leukopenia. Dose limiting toxicities included grade 4 neutropenia and grade 3 thrombocytopenia and dehydration. No patients had an objective response to palbociclib therapy. CONCLUSIONS: Palbociclib was safely administered to children and adolescents at a dosage of 75 mg/m2 for 21 consecutive days followed by seven days of rest in both strata. Future studies will establish its optimal utilization in pediatric patients with brain tumors.
Authors
Van Mater, D; Gururangan, S; Becher, O; Campagne, O; Leary, S; Phillips, JJ; Huang, J; Lin, T; Poussaint, TY; Goldman, S; Baxter, P; Dhall, G; Robinson, G; DeWire-Schottmiller, M; Hwang, EI; Stewart, CF; Onar-Thomas, A; Dunkel, IJ; Fouladi, M
MLA Citation
Van Mater, David, et al. “A phase I trial of the CDK 4/6 inhibitor palbociclib in pediatric patients with progressive brain tumors: A Pediatric Brain Tumor Consortium study (PBTC-042).Pediatr Blood Cancer, vol. 68, no. 4, Apr. 2021, p. e28879. Pubmed, doi:10.1002/pbc.28879.
URI
https://scholars.duke.edu/individual/pub1471176
PMID
33405376
Source
pubmed
Published In
Pediatr Blood Cancer
Volume
68
Published Date
Start Page
e28879
DOI
10.1002/pbc.28879

Molecular and phenotypic diversity of CBL-mutated juvenile myelomonocytic leukemia.

Mutations in the gene CBL were first identified in adults with various myeloid malignancies. Some patients with juvenile myelomonocytic leukemia (JMML) were also noted to harbor mutations in CBL, but were found to have generally less aggressive disease courses compared to other forms of Ras pathway-mutant JMML. Importantly, and in contrast to most reports in adults, the majority of CBL mutations in JMML patients are germline with acquired uniparental disomy occurring in affected marrow cells. Here, we systematically studied a large cohort of 33 JMML patients with CBL mutations and found this disease to be highly diverse in presentation and overall outcome. Moreover, we discovered somatically-acquired CBL mutations in 15% of pediatric patients who presented with more aggressive disease. Neither clinical features nor methylation profiling were able to distinguish somatic CBL patients from germline CBL patients, highlighting the need for germline testing. Overall, we demonstrate that disease courses are quite heterogeneous even among germline CBL patients. Prospective clinical trials are warranted to find ideal treatment strategies for this diverse cohort of patients.
Authors
Hecht, A; Meyer, JA; Behnert, A; Wong, E; Chehab, F; Olshen, A; Hechmer, A; Aftandilian, C; Bhat, R; Choi, SW; Chonat, S; Farrar, JE; Fluchel, M; Frangoul, H; Han, JH; Kolb, EA; Kuo, DJ; MacMillan, ML; Maese, L; Maloney, KW; Narendran, A; Oshrine, B; Schultz, KR; Sulis, ML; Van Mater, D; Tasian, SK; Hofmann, W-K; Loh, ML; Stieglitz, E
MLA Citation
Hecht, Anna, et al. “Molecular and phenotypic diversity of CBL-mutated juvenile myelomonocytic leukemia.Haematologica, vol. 107, no. 1, Jan. 2022, pp. 178–86. Pubmed, doi:10.3324/haematol.2020.270595.
URI
https://scholars.duke.edu/individual/pub1472590
PMID
33375775
Source
pubmed
Published In
Haematologica
Volume
107
Published Date
Start Page
178
End Page
186
DOI
10.3324/haematol.2020.270595

Receptor tyrosine kinase inhibitors for the treatment of osteosarcoma and Ewing sarcoma.

Adjuvant chemotherapy for osteosarcoma and Ewing sarcoma consists of conventional cytotoxic regimens that have changed little over the past decades. There is an urgent need for agents that are more effective and have less long-term toxicity. Receptor tyrosine kinases regulate cell growth and proliferation of these tumors, and small-molecule inhibitors for many of these kinases are now available. In this article, we review published phase II trials for patients with recurrent disease and highlight the pathways targeted by available agents, as well as the toxicity and efficacy results seen to date. We also discuss the difficulties in identifying biomarkers to facilitate rational patient selection, as well as published and proposed strategies for how these inhibitors can be combined with conventional chemotherapy or other targeted agents. It is hoped future trials can capitalize on this growing experience to optimize the use of this exciting class of agents.
Authors
MLA Citation
Just, Marissa A., et al. “Receptor tyrosine kinase inhibitors for the treatment of osteosarcoma and Ewing sarcoma.Pediatr Blood Cancer, vol. 68, no. 8, Aug. 2021, p. e29084. Pubmed, doi:10.1002/pbc.29084.
URI
https://scholars.duke.edu/individual/pub1482407
PMID
33894051
Source
pubmed
Published In
Pediatr Blood Cancer
Volume
68
Published Date
Start Page
e29084
DOI
10.1002/pbc.29084

Research Areas:

Neurofibromatosis
Neurofibromatosis 1
Neurofibromatosis 2
Neurofibromatosis in children
Oncology
Sarcoma
Tumors in children