Zachary Reitman

Overview:

Dr. Reitman’s clinical interests include radiotherapy for primary and metastatic tumors of the brain and spine.  He is also interested in basic and translational research studies to develop new treatment approaches for pediatric and adult brain tumors.  He uses genomic analysis, radiation biology studies, and genetically engineered animal models of cancer to carry out this research

Positions:

Assistant Professor of Radiation Oncology

Radiation Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2012

Duke University School of Medicine

M.D. 2014

Duke University School of Medicine

Internship, Internal Medicine

Union Memorial Hospital

Resident, Radiation Oncology

Massachusetts General Hospital

Grants:

Prioritizing PPM1D mutations as a target for new DIPG therapies

Administered By
Radiation Oncology
Awarded By
Michael Mosier Defeat DIPG Foundation
Role
Principal Investigator
Start Date
End Date

Generation of a genetically-modified microorganism for adipic acid production

Administered By
Pathology
Awarded By
North Carolina Biotechnology Center
Role
Principal Investigator
Start Date
End Date

Identifying brainstem glioma subtypes that can be radiosensitized by ATM inhibition

Administered By
Radiation Oncology
Awarded By
Pediatric Brain Tumor Foundation
Role
Principal Investigator
Start Date
End Date

Enhancing the efficacy of radiation therapy for DIPG

Administered By
Radiation Oncology
Awarded By
Michael Mosier Defeat DIPG Foundation
Role
Principal Investigator
Start Date
End Date

Enhancing the efficacy of radiation therapy for brainstem gliomas

Administered By
Radiation Oncology
Awarded By
St. Baldrick's Foundation
Role
PI-Fellow
Start Date
End Date

Publications:

Picornavirus genome replication. Identification of the surface of the poliovirus (PV) 3C dimer that interacts with PV 3Dpol during VPg uridylylation and construction of a structural model for the PV 3C2-3Dpol complex.

Picornaviruses have a peptide termed VPg covalently linked to the 5'-end of the genome. Attachment of VPg to the genome occurs in at least two steps. First, Tyr-3 of VPg, or some precursor thereof, is used as a primer by the viral RNA-dependent RNA polymerase, 3Dpol, to produce VPg-pUpU. Second, VPg-pUpU is used as a primer to produce full-length genomic RNA. Production of VPg-pUpU is templated by a single adenylate residue located in the loop of an RNA stem-loop structure termed oriI by using a slide-back mechanism. Recruitment of 3Dpol to and its stability on oriI have been suggested to require an interaction between the back of the thumb subdomain of 3Dpol and an undefined region of the 3C domain of viral protein 3CD. We have performed surface acidic-to-alanine-scanning mutagenesis of 3C to identify the surface of 3C with which 3Dpol interacts. This analysis identified numerous viable poliovirus mutants with reduced growth kinetics that correlated to reduced kinetics of RNA synthesis that was attributable to a change in VPg-pUpU production. Importantly, these 3C derivatives were all capable of binding to oriI as well as wild-type 3C. Synthetic lethality was observed for these mutants when placed in the context of a poliovirus mutant containing 3Dpol-R455A, a residue on the back of the thumb required for VPg uridylylation. These data were used to guide molecular docking of the structures for a poliovirus 3C dimer and 3Dpol, leading to a structural model for the 3C(2)-3Dpol complex that extrapolates well to all picornaviruses.
Authors
Shen, M; Reitman, ZJ; Zhao, Y; Moustafa, I; Wang, Q; Arnold, JJ; Pathak, HB; Cameron, CE
URI
https://scholars.duke.edu/individual/pub998134
PMID
17993457
Source
pubmed
Published In
The Journal of Biological Chemistry
Volume
283
Published Date
Start Page
875
End Page
888
DOI
10.1074/jbc.M707907200

Promoting a new brain tumor mutation: TERT promoter mutations in CNS tumors.

MLA Citation
Reitman, Zachary J., et al. “Promoting a new brain tumor mutation: TERT promoter mutations in CNS tumors.Acta Neuropathol, vol. 126, no. 6, Dec. 2013, pp. 789–92. Pubmed, doi:10.1007/s00401-013-1207-5.
URI
https://scholars.duke.edu/individual/pub999782
PMID
24217890
Source
pubmed
Published In
Acta Neuropathol
Volume
126
Published Date
Start Page
789
End Page
792
DOI
10.1007/s00401-013-1207-5

Releasing the block: setting differentiation free with mutant IDH inhibitors.

Hotspot mutations in IDH1 and IDH2 cause a differentiation block that can promote tumorigenesis. Two recent papers reported that small molecules targeting mutant IDH1 or mutant IDH2 release this differentiation block and/or impede tumor growth, providing a proof-of-concept that mutant IDHs are therapeutically targetable and that their effects are reversible.
MLA Citation
Pirozzi, Christopher J., et al. “Releasing the block: setting differentiation free with mutant IDH inhibitors.Cancer Cell, vol. 23, no. 5, May 2013, pp. 570–72. Pubmed, doi:10.1016/j.ccr.2013.04.024.
URI
https://scholars.duke.edu/individual/pub948113
PMID
23680144
Source
pubmed
Published In
Cancer Cell
Volume
23
Published Date
Start Page
570
End Page
572
DOI
10.1016/j.ccr.2013.04.024

TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal.

Malignant cells, like all actively growing cells, must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the telomere binding proteins alpha thalassemia/mental retardation syndrome X-linked (ATRX) or death-domain associated protein (DAXX) have been shown to underlie a telomere maintenance mechanism not involving telomerase (alternative lengthening of telomeres), and point mutations in the promoter of the telomerase reverse transcriptase (TERT) gene increase telomerase expression and have been shown to occur in melanomas and a small number of other tumors. To further define the tumor types in which this latter mechanism plays a role, we surveyed 1,230 tumors of 60 different types. We found that tumors could be divided into types with low (<15%) and high (≥15%) frequencies of TERT promoter mutations. The nine TERT-high tumor types almost always originated in tissues with relatively low rates of self renewal, including melanomas, liposarcomas, hepatocellular carcinomas, urothelial carcinomas, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas (including 83% of primary glioblastoma, the most common brain tumor type). TERT and ATRX mutations were mutually exclusive, suggesting that these two genetic mechanisms confer equivalent selective growth advantages. In addition to their implications for understanding the relationship between telomeres and tumorigenesis, TERT mutations provide a biomarker that may be useful for the early detection of urinary tract and liver tumors and aid in the classification and prognostication of brain tumors.
Authors
Killela, PJ; Reitman, ZJ; Jiao, Y; Bettegowda, C; Agrawal, N; Diaz, LA; Friedman, AH; Friedman, H; Gallia, GL; Giovanella, BC; Grollman, AP; He, T-C; He, Y; Hruban, RH; Jallo, GI; Mandahl, N; Meeker, AK; Mertens, F; Netto, GJ; Rasheed, BA; Riggins, GJ; Rosenquist, TA; Schiffman, M; Shih, I-M; Theodorescu, D; Torbenson, MS; Velculescu, VE; Wang, T-L; Wentzensen, N; Wood, LD; Zhang, M; McLendon, RE; Bigner, DD; Kinzler, KW; Vogelstein, B; Papadopoulos, N; Yan, H
MLA Citation
Killela, Patrick J., et al. “TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal.Proc Natl Acad Sci U S A, vol. 110, no. 15, Apr. 2013, pp. 6021–26. Pubmed, doi:10.1073/pnas.1303607110.
URI
https://scholars.duke.edu/individual/pub932635
PMID
23530248
Source
pubmed
Published In
Proc Natl Acad Sci U S A
Volume
110
Published Date
Start Page
6021
End Page
6026
DOI
10.1073/pnas.1303607110

Exomic sequencing of four rare central nervous system tumor types.

A heterogeneous population of uncommon neoplasms of the central nervous system (CNS) cause significant morbidity and mortality. To explore their genetic origins, we sequenced the exomes of 12 pleomorphic xanthoastrocytomas (PXA), 17 non-brainstem pediatric glioblastomas (PGBM), 8 intracranial ependymomas (IEP) and 8 spinal cord ependymomas (SCEP). Analysis of the mutational spectra revealed that the predominant single base pair substitution was a C:G>T:A transition in each of the four tumor types. Our data confirm the critical roles of several known driver genes within CNS neoplasms, including TP53 and ATRX in PGBM, and NF2 in SCEPs. Additionally, we show that activating BRAF mutations play a central role in both low and high grade glial tumors. Furthermore, alterations in genes coding for members of the mammalian target of rapamycin (mTOR) pathway were observed in 33% of PXA. Our study supports the hypothesis that pathologically similar tumors arising in different age groups and from different compartments may represent distinct disease processes with varied genetic composition.
Authors
Bettegowda, C; Agrawal, N; Jiao, Y; Wang, Y; Wood, LD; Rodriguez, FJ; Hruban, RH; Gallia, GL; Binder, ZA; Riggins, CJ; Salmasi, V; Riggins, GJ; Reitman, ZJ; Rasheed, A; Keir, S; Shinjo, S; Marie, S; McLendon, R; Jallo, G; Vogelstein, B; Bigner, D; Yan, H; Kinzler, KW; Papadopoulos, N
MLA Citation
Bettegowda, Chetan, et al. “Exomic sequencing of four rare central nervous system tumor types.Oncotarget, vol. 4, no. 4, Apr. 2013, pp. 572–83. Pubmed, doi:10.18632/oncotarget.964.
URI
https://scholars.duke.edu/individual/pub952544
PMID
23592488
Source
pubmed
Published In
Oncotarget
Volume
4
Published Date
Start Page
572
End Page
583
DOI
10.18632/oncotarget.964

Research Areas:

Cancer
Ganglioglioma
Genomics
Glioma
Molecular Biology
Molecular radiobiology
Radiotherapy
Single Cell Biology