Francis Ali-Osman

Positions:

Margaret Harris and David Silverman Professor of Neuro-Oncology Research

Neurosurgery, Neuro-Oncology
School of Medicine

Professor Emeritus in Neurosurgery

Neurosurgery, Neuro-Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

D.Sc. 1982

Free University of Berlin (Germany)

Grants:

P53-dependent GSTP1 Gene Regulation and Glioma Drug Resistance

Administered By
Surgery, Surgical Sciences
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Protein Kinase C and GSTP1 interactions in glioma drug resistance

Administered By
Surgery, Surgical Sciences
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

Role of monoamine-oxidase-A-gene variation in the development of glioblastoma in males: a case control study.

BACKGROUND: The Mono-amine oxidase-A (MAO-A) enzyme is involved in the degradation and regulation of catecholamines such as serotonin, dopamine, epinephrine and nor-epinephrine. Preclinical studies suggest that this enzyme may contribute to an environment favorable for growth of malignant glioma. The MAO-A gene is located on the X-chromosome and has at least one functional genetic polymorphism. The aim of the present study was to explore possible effects of MAO-A genotype on development of glioblastoma in males. METHODS: Genotypes for 437 glioma cases and 876 population-based controls from the Swedish Glioma International Case-Control study (GICC) were compared. We analyzed the germline DNA using the Illumina Oncoarray. We selected seven single nucleotide polymorphisms (SNPs) located in the MAO-A gene, and imputed genotypes based on data from the 1000 genomes project. We used 1579 male glioblastoma cases and 1875 controls comprising the whole GICC cohort for subsequent validation of findings. RESULTS: The rs144551722 SNP was a significant predictor of development of glioblastoma in males (p-value = 0.0056) but not in females even after correction for multiple testing. We conducted haplotype analysis to confirm an association between MAO-A gene and risk of glioblastoma (p-value = 0.016). We found similar results in the validation sample. CONCLUSIONS: These results suggest the possibility of a role for the MAO-A enzyme and the MAO-A gene in the development of glioblastoma in males.
Authors
Sjöberg, RL; Wu, WY-Y; Dahlin, AM; Tsavachidis, S; Gliogene Group,; Bondy, ML; Melin, B
MLA Citation
Sjöberg, Rickard L., et al. “Role of monoamine-oxidase-A-gene variation in the development of glioblastoma in males: a case control study..” J Neurooncol, vol. 145, no. 2, Nov. 2019, pp. 287–94. Pubmed, doi:10.1007/s11060-019-03294-w.
URI
https://scholars.duke.edu/individual/pub1422306
PMID
31556016
Source
pubmed
Published In
J Neurooncol
Volume
145
Published Date
Start Page
287
End Page
294
DOI
10.1007/s11060-019-03294-w

History of chickenpox in glioma risk: a report from the glioma international case-control study (GICC).

Varicella zoster virus (VZV) is a neurotropic α-herpesvirus that causes chickenpox and establishes life-long latency in the cranial nerve and dorsal root ganglia of the host. To date, VZV is the only virus consistently reported to have an inverse association with glioma. The Glioma International Case-Control Study (GICC) is a large, multisite consortium with data on 4533 cases and 4171 controls collected across five countries. Here, we utilized the GICC data to confirm the previously reported associations between history of chickenpox and glioma risk in one of the largest studies to date on this topic. Using two-stage random-effects restricted maximum likelihood modeling, we found that a positive history of chickenpox was associated with a 21% lower glioma risk, adjusting for age and sex (95% confidence intervals (CI): 0.65-0.96). Furthermore, the protective effect of chickenpox was stronger for high-grade gliomas. Our study provides additional evidence that the observed protective effect of chickenpox against glioma is unlikely to be coincidental. Future studies, including meta-analyses of the literature and investigations of the potential biological mechanism, are warranted.
Authors
Amirian, ES; Scheurer, ME; Zhou, R; Wrensch, MR; Armstrong, GN; Lachance, D; Olson, SH; Lau, CC; Claus, EB; Barnholtz-Sloan, JS; Il'yasova, D; Schildkraut, J; Ali-Osman, F; Sadetzki, S; Jenkins, RB; Bernstein, JL; Merrell, RT; Davis, FG; Lai, R; Shete, S; Amos, CI; Melin, BS; Bondy, ML
MLA Citation
Amirian, E. Susan, et al. “History of chickenpox in glioma risk: a report from the glioma international case-control study (GICC)..” Cancer Med, vol. 5, no. 6, June 2016, pp. 1352–58. Pubmed, doi:10.1002/cam4.682.
URI
https://scholars.duke.edu/individual/pub1125738
PMID
26972449
Source
pubmed
Published In
Cancer Medicine
Volume
5
Published Date
Start Page
1352
End Page
1358
DOI
10.1002/cam4.682

The mutational status of the p53 tumor suppressor gene is a determinant of GSTP1 expression and mediates GSTP1-dependent drug resistance in human glioblastoma

Authors
Antoun, GR; McLendon, R; Friedman, H; Friedman, A; Bigner, D; Ali-Osman, F
MLA Citation
Antoun, Gamil R., et al. “The mutational status of the p53 tumor suppressor gene is a determinant of GSTP1 expression and mediates GSTP1-dependent drug resistance in human glioblastoma.” Cancer Research, vol. 72, 2012. Wos-lite, doi:10.1158/1538-7445.AM2012-1177.
URI
https://scholars.duke.edu/individual/pub1131932
Source
wos-lite
Published In
Cancer Research
Volume
72
Published Date
DOI
10.1158/1538-7445.AM2012-1177

Decoupling of DNA damage response signaling from DNA damages underlies temozolomide resistance in glioblastoma cells.

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor in adults. Current therapy includes surgery, radiation and chemotherapy with temozolomide (TMZ). Major determinants of clinical response to TMZ include methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter and mismatch repair (MMR) status. Though the MGMT promoter is methylated in 45% of cases, for the first nine months of follow-up, TMZ does not change survival outcome. Furthermore, MMR deficiency makes little contribution to clinical resistance, suggesting that there exist unrecognized mechanisms of resistance. We generated paired GBM cell lines whose resistance was attributed to neither MGMT nor MMR. We show that, responding to TMZ, these cells exhibit a decoupling of DNA damage response (DDR) from ongoing DNA damages. They display methylation-resistant synthesis in which ongoing DNA synthesis is not inhibited. They are also defective in the activation of the S and G2 phase checkpoint. DDR proteins ATM, Chk2, MDC1, NBS1 and gammaH2AX also fail to form discrete foci. These results demonstrate that failure of DDR may play an active role in chemoresistance to TMZ. DNA damages by TMZ are repaired by MMR proteins in a futile, reiterative process, which activates DDR signaling network that ultimately leads to the onset of cell death. GBM cells may survive genetic insults in the absence of DDR. We anticipate that our findings will lead to more studies that seek to further define the role of DDR in ultimately determining the fate of a tumor cell in response to TMZ and other DNA methylators.
Authors
Cui, B; Johnson, SP; Bullock, N; Ali-Osman, F; Bigner, DD; Friedman, HS
MLA Citation
Cui, Bo, et al. “Decoupling of DNA damage response signaling from DNA damages underlies temozolomide resistance in glioblastoma cells..” J Biomed Res, vol. 24, no. 6, Nov. 2010, pp. 424–35. Pubmed, doi:10.1016/S1674-8301(10)60057-7.
URI
https://scholars.duke.edu/individual/pub757354
PMID
23554659
Source
pubmed
Published In
Journal of Biomedical Research
Volume
24
Published Date
Start Page
424
End Page
435
DOI
10.1016/S1674-8301(10)60057-7

Correction: Article on genomic and molecular profiling to predict response to temozolomide (Clinical Cancer Research (2009) 15, (502-510))

Authors
Augustine, CK; Yoo, JS; Potti, A; Yoshimoto, Y; Zipfel, PA; Friedman, HS; Nevins, JR; Ali-Osman, F; Tyler, DS
MLA Citation
Augustine, C. K., et al. “Correction: Article on genomic and molecular profiling to predict response to temozolomide (Clinical Cancer Research (2009) 15, (502-510)).” Clinical Cancer Research, vol. 15, no. 9, 1 May 2009. Scopus, doi:10.1158/1078-0432.CCR-15-9-COR.
URI
https://scholars.duke.edu/individual/pub757360
Source
scopus
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
15
Published Date
Start Page
3240
DOI
10.1158/1078-0432.CCR-15-9-COR