Role of Tumor Suppressor Gene Products of Common Fragile Sites in Human Diseases
Common fragile sites (CFSs) are large chromosomal regions identified by conventional cytogenetics as sequences prone to breakage in cells subjected to replication stress. The interest in CFSs stems from their key role in DNA damage, resulting in chromosomal rearrangements. The instability of CFSs was correlated with genome instability in precancerous lesions and during tumor progression. Two opposing views dominate the discussion regarding the role of CFSs. One school of thought suggested that genomic instability during cancer progression causes collateral damage to genes residing within CFSs, such as WWOX and FHIT. These genes are proposed to be unselected ‘‘passenger’’ mutations. The counter argument is that deletions and other genomic alterations in CFSs occur early in cancer development. Cancer cells with deletions in genes that span CFSs are then selectively expanded due to loss of tumor suppressor functions such as protection of genome stability, coordination of cell cycle or apoptosis.
Recent observations from our lab clearly suggest that gene products of CFSs play driver roles in cancer transformation. Furthermore, accumulating evidence links some of these products with metabolic diseases and neuropathy. Investigating the role of these gene products in human diseases is a major interest of our lab work. The ultimate goal of our research is hence to discover the genes and to elucidate the pathways that represent targets for the development of rational, specific and effective therapeutic approaches.
Dr. Lina Jaber/Abu-Tair, Lab Manager and Researcher
Dr. Idit Hazan, Research Associate
Dr. Srinivasarao Repudi, Post-Doc
Housam Husseini, PhD student
Rania Akkawi, PhD student
Daniel Steinberg, MD-PhD student
Hazem Safadi, MSc student
Aya Shwieki, MSc Student
Sara Oster, PhD student
Tirza Bidany, MSc student
Yariv Cohen, MSc
Thesis Title: “Functional Association between WWOX and p73 and their involvement in the tumorigenic process”
Tomer Barmag, MSc
Thesis Title: “Characterizing new partners of the WWOX tumor suppressor protein”
Ortal Iancu, MSc
Thesis Title: “Functional cross-talk between WWOX and c-Fos in osteosarcoma development”
Sheeri Cohen, MSc
Thesis Title: “Regulation of Hippo signaling via WW domain interactions”
Keren Shemesh, MSc
Thesis Title: “Regulation of Hippo signaling via WW domain interactions”
Rand Arafeh, MSc
Thesis Title: “Role of microRNA 27a in osteosarcoma development”
Ella Abktekov, MSc
Thesis Title: “Role of the ubiquitin E3 ligase ITCH in breast carcinogenesis”
Dr. Zaidoun Salah, Post-doc
Currently Associate Professor at Al-Quds University
Dr. Vadim Maximov, Post-doc
Dr. Gili Bester, Lab Manager and Researcher
Sara Del Mare, PhD
Thesis Title: “WWOX as Signal mediator in Osteosarcoma development”
Mohammad Abu-Odeh, PhD
Thesis Title: “Role of WWOX fragile gene in DNA damage response”
Suhaib Abdeen, PhD
Thesis Title: “Role of Tumor Suppressor WWOX in Mammary Gland Development and Tumorigenicity”
Muhannad Abu-Remaileh, PhD
Thesis Title: “Tumor Suppressor WWOX as a Key Modulator of Cellular Metabolism”
Saleh Khawaled, PhD
Thesis Title: “Molecular and Cellular Role of Tumor Suppressor WWOX in Breast Cancer Metastasis”
- Mapping the breakome of cancer cells
- Elucidating the role of gene products of CFSs in driving carcinogenesis
- Dissecting the role of various oncogenes in inducing replication stress
- Studying the role of the WWOX gene in cellular metabolism
- Determining the role of WWOX in epilepsy and ataxia
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Abu-Remaileh M, Aqeilan RI. Tumor suppressor WWOX regulates glucose metabolism via HIF1alpha modulation. Cell Death Differ 2014, 21(11): 1805-1814.
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Hazan I, Hofmann TG, Aqeilan RI. Tumor Suppressor Genes within Common Fragile Sites Are Active Players in the DNA Damage Response. PLoS Genet 2016, 12(12): e1006436.
Abu-Remaileh M, Khalaileh A, Pikarsky E, Aqeilan RI. WWOX controls hepatic HIF1alpha to suppress hepatocyte proliferation and neoplasia. Cell Death Dis 2018, 9(5): 511.
Abu-Remaileh M, Abu-Remaileh M, Akkawi R, Knani I, Udi S, Pacold ME, Tam J, Aqeilan RI. WWOX somatic ablation in skeletal muscles alters glucose metabolism. Mol Metab. 2019 Apr;22:132-140.
Khawaled S, Suh SS, Abdeen SK, Monin J, Distefano R, Nigita G, Croce CM, Aqeilan RI. WWOX Inhibits Metastasis of Triple-Negative Breast Cancer Cells via
Modulation of miRNAs. Cancer Res. 2019 Apr 15;79(8):1784-1798.
Commentary by Sharma, P.: Quest for Tangible Biomarkers for Triple-Negative Breast Cancer. [Cancer Res. 2019]
- Dr. Gary Stein, Director, Vermont Cancer Center, USA
- Dr. Jane Lian, Vermont Cancer Center, USA
- Dr. Victoria Seewaldt, City of Hope, USA
- Dr. Uri Ben-David, Broad Institute, USA
- Dr. Thomas Hofmann, University Medicine Mainz, Germany
- Dr. Peter Carlen, University of Toronto, Canada