Francis Ali-Osman

Positions:

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

Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Protein Kinase C and GSTP1 interactions in glioma drug resistance

Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

European genetic ancestry associated with risk of childhood ependymoma.

BACKGROUND: Ependymoma is a histologically defined central nervous system tumor most commonly occurring in childhood. Population-level incidence differences by race/ethnicity are observed, with individuals of European ancestry at highest risk. We aimed to determine whether extent of European genetic ancestry is associated with ependymoma risk in US populations. METHODS: In a multi-ethnic study of Californian children (327 cases, 1970 controls), we estimated the proportions of European, African, and Native American ancestry among recently admixed Hispanic and African American subjects and estimated European admixture among non-Hispanic white subjects using genome-wide data. We tested whether genome-wide ancestry differences were associated with ependymoma risk and performed admixture mapping to identify associations with local ancestry. We also evaluated race/ethnicity-stratified ependymoma incidence data from the Central Brain Tumor Registry of the United States (CBTRUS). RESULTS: CBTRUS data revealed that African American and Native American children have 33% and 36%, respectively, reduced incidence of ependymoma compared with non-Hispanic whites. In genetic analyses, a 20% increase in European ancestry was associated with a 1.31-fold higher odds of ependymoma among self-reported Hispanics and African Americans (95% CI: 1.08-1.59, Pmeta = 6.7 × 10-3). Additionally, eastern European ancestral substructure was associated with increased ependymoma risk in non-Hispanic whites (P = 0.030) and in Hispanics (P = 0.043). Admixture mapping revealed a peak at 20p13 associated with increased local European ancestry, and targeted fine-mapping identified a lead variant at rs6039499 near RSPO4 (odds ratio = 1.99; 95% CI: 1.45-2.73; P = 2.2 × 10-5) but which was not validated in an independent set of posterior fossa type A patients. CONCLUSIONS: Interethnic differences in ependymoma risk are recapitulated in the genomic ancestry of ependymoma patients, implicating regions to target in future association studies.
Authors
Zhang, C; Ostrom, QT; Hansen, HM; Gonzalez-Maya, J; Hu, D; Ziv, E; Morimoto, L; de Smith, AJ; Muskens, IS; Kline, CN; Vaksman, Z; Hakonarson, H; Diskin, SJ; Kruchko, C; Barnholtz-Sloan, JS; Ramaswamy, V; Ali-Osman, F; Bondy, ML; Taylor, MD; Metayer, C; Wiemels, JL; Walsh, KM
MLA Citation
Zhang, Chenan, et al. “European genetic ancestry associated with risk of childhood ependymoma.Neuro Oncol, vol. 22, no. 11, Nov. 2020, pp. 1637–46. Pubmed, doi:10.1093/neuonc/noaa130.
URI
https://scholars.duke.edu/individual/pub1432904
PMID
32607579
Source
pubmed
Published In
Neuro Oncol
Volume
22
Published Date
Start Page
1637
End Page
1646
DOI
10.1093/neuonc/noaa130

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

Long-Term Follow-up Results: A Phase 2 Trial of Imatinib Mesylate As Maintenance Therapy for Patients with Newly Diagnosed c-Kit Positive Acute Myeloid Leukemia (AML)

Authors
Advani, AS; Tse, W; Jia, X; Elson, P; Cooper, B; Ali-Osman, F; Park, J; Rao, AV; Rizzieri, DA; Wang, ES; Cotta, CV; Kalaycio, M; Sobecks, RM; Rouphail, B; Maciejewski, JP; Fensterl, J; Bailey, L; Carew, JS; Foster, B; Rush, ML; Adams, D; Griffiths, EA; Sekeres, MA
URI
https://scholars.duke.edu/individual/pub1123350
Source
wos
Published In
Blood
Volume
126
Published Date

UPREGULATION OF VEGF-A GENE EXPRESSION BY THE tGLI1 TRANSCRIPTION FACTOR CONTRIBUTES TO GLIOBLASTOMA ANGIOGENESIS

Authors
MLA Citation
Zhu, Hu, et al. “UPREGULATION OF VEGF-A GENE EXPRESSION BY THE tGLI1 TRANSCRIPTION FACTOR CONTRIBUTES TO GLIOBLASTOMA ANGIOGENESIS.” Neuro Oncology, vol. 13, OXFORD UNIV PRESS INC, 2011, pp. I15–16.
URI
https://scholars.duke.edu/individual/pub928406
Source
wos
Published In
Neuro Oncology
Volume
13
Published Date
Start Page
I15
End Page
I16

Gene expression signatures as a guide to treatment strategies for in-transit metastatic melanoma.

In-transit metastatic melanoma, which typically presents as multifocal lesions, provides a unique setting to evaluate the utility of gene signatures for defining optimal regional therapeutic strategies and assessing the efficacy of treatment. The goal of this study was to determine whether a single multifocal lesion is representative of residual tumor burden in terms of gene expression signatures predictive of response to therapy. Using microarray-based gene expression profiling, we examined 55 in-transit melanoma lesions across 29 patients with multifocal disease. Principal component analysis, unsupervised hierarchical clustering, one-way ANOVA, binary regression analysis, and gene signatures predictive of oncogenic pathway activation were used to compare patterns of gene expression across all multifocal lesions from a patient. Patterns of gene expression were highly similar (P < 0.006; average r = 0.979) across pretreatment lesions from a single patient compared with the significantly different patterns observed across patients (P < 0.05). The findings presented in this study show that individual melanoma tumor nodules in patients with multifocal disease harbor similar patterns of gene expression and a single lesion can be used to predict response to chemotherapy, evaluate the activation status of oncogenic signaling pathways, and characterize other aspects of the biology of an individual patient's disease. These results will facilitate the use of gene expression profiling in melanoma regional therapy clinical trials to not only select optimal regional chemotherapeutic agents but to also allow for a more rational identification of candidates for specific targeted therapies and evaluation of their therapeutic efficacy. Mol Cancer Ther; 9(4); 779-90. (c)2010 AACR.
Authors
Augustine, CK; Jung, S-H; Sohn, I; Yoo, JS; Yoshimoto, Y; Olson, JA; Friedman, HS; Ali-Osman, F; Tyler, DS
MLA Citation
Augustine, Christina K., et al. “Gene expression signatures as a guide to treatment strategies for in-transit metastatic melanoma.Mol Cancer Ther, vol. 9, no. 4, Apr. 2010, pp. 779–90. Pubmed, doi:10.1158/1535-7163.MCT-09-0764.
URI
https://scholars.duke.edu/individual/pub757358
PMID
20371714
Source
pubmed
Published In
Mol Cancer Ther
Volume
9
Published Date
Start Page
779
End Page
790
DOI
10.1158/1535-7163.MCT-09-0764