المراحل الدراسية

  • Degree بكالوريوس 2002

    علوم حياتية

    جامعة آل البيت

  • Master ماجستير 2012

    ماجستير في العلوم

    Ruprecht Karls Universität Heidelberg

  • Ph.D دكتوراه 2016

    دكتوراة في العلوم

    Ruprecht Karls Universität Heidelberg

الانشطة الاكاديمية

  • 3/22/2016

    ARC16 مؤتمر مؤسسة قطر للعلوم السنوي

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    المشاركة بمؤتمر | قطر | بمفردي | اللغة الانجليزية

  • 3/27/2015

    Training in Roche “LightCycler 480 Real Time PCR Systems”

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    المشاركة بدورة | ألمانيا | بمفردي | اللغة الانجليزية Roche Company

  • 5/22/2015

    4th Heidelberg Forum for Young Life Scientists

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    | ألمانيا | ضمن فريق | اللغة الانجليزية A molecular Battlefield

  • 3/23/2015

    career day for Clinical Research and Regulatory AffairsC.

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    المشاركة بدورة | ألمانيا | بمفردي | اللغة الانجليزية

  • 9/9/2014

    Supervision : MSc students from the Cancer program at DKFZ: Project design, tutorials, seminars, reports, revision, and evaluation

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    | ألمانيا | بمفردي | اللغة الانجليزية

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    PhD retreat

    كونفرنس علمي مكثف لمدة ٣ أيام لطلاب الدكتوراة في مركز السرطان الألماني يقومون فيه بعرض ومناقشة أبحاث

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    Poster presentation

    عرض لوحة عن مشروع الدكتوراة في مركز السرطان الألماني عن microRNA regulation in pancreatic cancer

    Pancreatic cancer is one of the leading causes of cancer-related mortality worldwide and is highly therapy-resistant, e.g. toward the standard chemotherapy gemcitabine. MicroRNAs are a group of small non-coding RNAs that post transcriptionally regulate gene expression. In this study, I evaluated the effect of DEX on the microRNA profile of pancreatic cancer cell lines. By microRNA array I observed a deregulation of several miRNAs. The most significantly deregulated miRNA, miR-XYZ was predicted to target key members of the TGFß pathway. Forced expression of this miR-XYZ by liposomal transfection of mimics resulted in significant repression of TGFß-X mRNA and protein levels.3’UTR luciferasereporter- and site-directed mutagenesis assays confirmed TGFß-X to be a direct target of miR-XYZ. Functionally, I found that miR-XYZ significantly reduced proliferation, migration and colony formation. My preliminarily in vivo data show that miR-XYZ reduces tumor xenograft tumor growth in vivo . I conclude that miR-XYZ is a tumor suppressor gene that inhibits EMT by regulating oncogenes and/or genes that control EMT.

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Up-regulation of microRNA Let-7c by quercetin inhibits pancreatic cancer progression by activation of Numbl

Clifford C. Nwaeburu, Natalie Bauer, Zhefu Zhao, Alia Abukiwan, Jury Gladkich, Axel Benner2, Ingrid Herr1
0 Oncotarget, , , 2016,

Abstract | ملخص البحث

Pancreatic Ductal Adenocarcinoma (PDA) is a highly malignant tumor with poor prognosis. MicroRNAs (miRs) may offer novel therapeutic approaches to treatment. The polyphenol quercetin, present in many fruits and vegetables, possesses anti- carcinogenic properties. To unravel the effect of quercetin to miR signaling we performed miR profiling in PDA cells before and after quercetin treatment, followed by biostatistical analysis. miR let-7c was among the top up-regulated candidates after quercetin treatment, as measured by qRT-PCR and confirmed in two established and one primary PDA cell lines. By computational analysis we identified the Notch- inhibitor Numbl as let-7c target gene. This was strengthened by luciferase assays, where lipofected let-7c mimics induced a Numbl 3-UTR wild type construct, but not the mutated counterpart. Let-7c induced Numbl mRNA and protein expression but inhibited Notch just like quercetin. It also inhibited colony formation, wound healing, and protein expression of progression markers. In vivo xenotransplantation of PDA cells and subsequent intravenous injection of let-7c resulted in a significant decrease in tumor mass without obvious toxic effects in the fertilized chick egg model. The delivery rate of the miR mimics to the tumor mass was 80%, whereas minor amounts were present in host tissue. By immunohistochemistry we demonstrated that let-7c inhibited Notch and progression markers but up-regulated Numbl. These findings show that quercetin-induced let-7c decreases tumor growth by posttranscriptional activation of Numbl and indirect inhibition of Notch.

miR-101-3p reverses gemcitabine resistance by inhibition of ribonucleotide reductase M1 in pancreatic cancer

Pei Fan, Li Liu, Yefeng Yin, Zhefu Zhao, Yiyao Zhang, Prince S. Amponsah, Xi Jury Gladkich, Xiao, Nathalie Bauer, Alia Abukiwan, Clifford C. Nwaeburu, Chao Gao, Peter Schemmer, Wolfgang Gross, Ingrid Herr
0 Cancer letter , 373, , 2016, 130-137

Abstract | ملخص البحث

Pancreatic ductal adenocarcinoma (PDA) is among the most lethal malignancies and resistance to chemotherapy prevents the therapeutic outcome. MicroRNAs provide a novel therapeutic strategy. Here, the established and primary human PDA cell lines PANC-1, AsPC-1, MIA-PaCa2, AsanPaCa, BxPC-3 and three gemcitabine-resistant subclones were examined. A gene expression profiling revealed that the ribonucleotide reductase M1 (RRM1) was upregulated in gemcitabine-resistant cells, which was confirmed by qRT-PCR, Western blot analysis and immunostaining. Inhibition of RRM1 by lipotransfection of siRNA reduced its expression and reversed gemcitabine resistance. The expression of RRM1 correlated to gemcitabine resistance in vitro and was higher in malignant patient pancreas tissue compared to non-malignant pancreas tissue. By microRNA expression profiling, we identified microRNA-101-3p as top-downregulated candidate. Lipotransfection of microRNA-101-3p mimics inhibited the expression of RRM1, reduced the luciferase activity of its 3'UTR and sensitized for gemcitabine-induced cytotoxicity. These results underline the relevance of microRNA-101-3p-driven regulation of RRM1 in drug resistance and suggest the co-delivery of microRNA-101-3p and gemcitabine for more effective therapy outcome.

miR-137 inhibits proliferation of melanoma cells by targeting PAK2.

Shuai Hao, Chonglin Luo, Alia Abukiwan, Guangxia Wang, Jinjun He, Lingyun Huang, Claudia E. M. Weber, Na Lv, Xueyuan Xiao, Stefan B. Eichmüller, Dacheng He
0 Experimental Dermatology , 24, 12, 2015, 947-52.

Abstract | ملخص البحث

MicroRNAs (miRNA) are key players in a variety of cancers including malignant melanoma. miR-137 has been reported to be a tumor suppressor in melanoma and several targets have been identified for this miRNA. We previously developed a novel proteomics technology, (35) S in vivo/vitro labelling analysis for dynamic proteomics (SiLAD). Because of its high sensitivity in analysing protein expression rates, SiLAD has the potential to unravel miRNA effects on mRNAs coding for proteins with long half-lives or high abundance. Using SiLAD, we discovered that miR-137 significantly downregulated the expression rate of p21-activated kinase 2 (PAK2) in melanoma cells. Bioinformatics analysis predicted PAK2 as a direct target of miR-137, which was confirmed by luciferase reporter assay and Western blot analysis. We found that overexpression of miR-137 inhibited the proliferation of melanoma cells, which could be phenocopied by knockdown of PAK2 using siRNAs. Furthermore, overexpression of PAK2 restored miR-137-mediated suppression of cell proliferation. These findings indicate that miR-137 could inhibit proliferation through targeting PAK2 in melanoma cells.

miR-137 inhibits the invasion of melanoma cells through downregulation of multiple oncogenic target genes.

Luo C1, Tetteh PW, Merz PR, Dickes E, Abukiwan A, Hotz-Wagenblatt A, Holland-Cunz S, Sinnberg T, Schittek B, Schadendorf D, Diederichs S, Eichmüller SB.
0 Journal of Investigative Dermatology , Volume 133, Issue 3, 2012, Pages 768

Abstract | ملخص البحث

MicroRNAs are small noncoding RNAs that regulate gene expression and have important roles in various types of cancer. Previously, miR-137 was reported to act as a tumor suppressor in different cancers, including malignant melanoma. In this study, we show that low miR-137 expression is correlated with poor survival in stage IV melanoma patients. We identified and validated two genes (c-Met and YB1) as direct targets of miR-137 and confirmed two previously known targets, namely enhancer of zeste homolog 2 (EZH2) and microphthalmia-associated transcription factor (MITF). Functional studies showed that miR-137 suppressed melanoma cell invasion through the downregulation of multiple target genes. The decreased invasion caused by miR-137 overexpression could be phenocopied by small interfering RNA knockdown of EZH2, c-Met, or Y box–binding protein 1 (YB1). Furthermore, miR-137 inhibited melanoma cell migration and proliferation. Finally, miR-137 induced apoptosis in melanoma cell lines and decreased BCL2 levels. In summary, our study confirms that miR-137 acts as a tumor suppressor in malignant melanoma and reveals that miR-137 regulates multiple targets including c-Met, YB1, EZH2, and MITF.

التدريس الحالي

  • الى الان 2015

    Animal Replacement / Reduction: Personalized models for pancreatic cancer on chick eggs instead of mice

    تدريب وتعليم مادة العملي في زراعة الأورام على أجنة الدجاج

الخبرة التدريسية