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

Proteomic profiling of patient-derived glioblastoma xenografts identifies a subset with activated EGFR: implications for drug development.

The development of drugs to inhibit glioblastoma (GBM) growth requires reliable pre-clinical models. To date, proteomic level validation of widely used patient-derived glioblastoma xenografts (PDGX) has not been performed. In the present study, we characterized 20 PDGX models according to subtype classification based on The Cancer Genome Atlas criteria, TP53, PTEN, IDH 1/2, and TERT promoter genetic analysis, EGFR amplification status, and examined their proteomic profiles against those of their parent tumors. The 20 PDGXs belonged to three of four The Cancer Genome Atlas subtypes: eight classical, eight mesenchymal, and four proneural; none neural. Amplification of EGFR gene was observed in 9 of 20 xenografts, and of these, 3 harbored the EGFRvIII mutation. We then performed proteomic profiling of PDGX, analyzing expression/activity of several proteins including EGFR. Levels of EGFR phosphorylated at Y1068 vary considerably between PDGX samples, and this pattern was also seen in primary GBM. Partitioning of 20 PDGX into high (n = 5) and low (n = 15) groups identified a panel of proteins associated with high EGFR activity. Thus, PDGX with high EGFR activity represent an excellent pre-clinical model to develop therapies for a subset of GBM patients whose tumors are characterized by high EGFR activity. Further, the proteins found to be associated with high EGFR activity can be monitored to assess the effectiveness of targeting EGFR. The development of drugs to inhibit glioblastoma (GBM) growth requires reliable pre-clinical models. We validated proteomic profiles using patient-derived glioblastoma xenografts (PDGX), characterizing 20 PDGX models according to subtype classification based on The Cancer Genome Atlas (TCGA) criteria, TP53, PTEN, IDH 1/2, and TERT promoter genetic analysis, EGFR amplification status, and examined their proteomic profiles against those of their parent tumors. Proteins found to be associated with high EGFR activity represent potential biomarkers for GBM monitoring.
Authors
Brown, KE; Chagoya, G; Kwatra, SG; Yen, T; Keir, ST; Cooter, M; Hoadley, KA; Rasheed, A; Lipp, ES; Mclendon, R; Ali-Osman, F; Bigner, DD; Sampson, JH; Kwatra, MM
MLA Citation
Brown, Kristine E., et al. “Proteomic profiling of patient-derived glioblastoma xenografts identifies a subset with activated EGFR: implications for drug development.J Neurochem, vol. 133, no. 5, June 2015, pp. 730–38. Pubmed, doi:10.1111/jnc.13032.
URI
https://scholars.duke.edu/individual/pub1056347
PMID
25598002
Source
pubmed
Published In
J Neurochem
Volume
133
Published Date
Start Page
730
End Page
738
DOI
10.1111/jnc.13032

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

IDENTIFICATION AND FUNCTIONAL CHARACTERIZATION OF THE HUMAN GSTP1 GENE AS A NOVEL TRANSCRIPTIONAL TARGET OF THE P53 TUMOR SUPPRESSOR GENE

Authors
Lo, H-W; Stephenson, L; Cao, X; Pollock, R; Milas, M; Ali-Osman, F
MLA Citation
Lo, Hui-Wen, et al. “IDENTIFICATION AND FUNCTIONAL CHARACTERIZATION OF THE HUMAN GSTP1 GENE AS A NOVEL TRANSCRIPTIONAL TARGET OF THE P53 TUMOR SUPPRESSOR GENE.” Neuro Oncology, vol. 10, no. 5, OXFORD UNIV PRESS INC, 2008, pp. 766–766.
URI
https://scholars.duke.edu/individual/pub928360
Source
wos
Published In
Neuro Oncology
Volume
10
Published Date
Start Page
766
End Page
766