פרופ' יוסף שילה

גנטיקה מולשל אדם וביוכמ אמריטוס
ניווט מהיר:
פרופ' יוסף שילה
טלפון פנימי: 03-6409760
פקס: 03-6407471
משרד: רפואה-סאקלר, 1002

Positions

Professor, Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University

David and Inez Myers Chair in Cancer Genetics

ICRF Research Professorship

 

Biography

Education

1971 - 1974    B.Sc. in Biology with distinction Technion - Israel Institute of Technology
1975 - 1977 M.Sc. in Human Genetics with distinction  Hebrew University of Jerusalem
1978 - 1983 Ph.D. in Human Genetics Hebrew University of Jerusalem

 

Research

The ATM-Mediated DNA Damage Response

Our laboratory investigates the cellular DNA damage response. This research stems from our interest in the human genetic disorder ataxia-telangiectasia (A-T), in which a central axis of the DNA damage response is missing.

 

Genetic defects in the DNA damage response lead to genomic instability syndromes, which usually include tissue degeneration, cancer predisposition, and sensitivity to specific DNA damaging agents. A prototype genomic instability syndrome is A-T. The disease is characterized by neuronal degeneration, immunodeficiency, chromosomal instability, sensitivity to ionizing radiation, and cancer predisposition. Our lab has been investigating A-T since its establishment in 1985. In 1995, after 8 years of intensive work, we identified the gene that is defective (mutated) in A-T patients and called it ATM (A-T, Mutated). We went on to study the activity of its product, the ATM protein, which turned out to be an enzyme with an activity alled "protein kinase".

 

Our current research is aimed at a broader understanding of the ATM-mediated DNA damage response. Particular attention is paid to the molecular and physiological basis of A-T, which may eventually lead to new treatment modalities for the disease. We investigate this system with cell biology methods, gene targeting in mice, and systems biology strategies including high-throughput screens, advanced proteomics and bioinformatics. A study is underway aimed at understanding the DNA damage response in the part of the brain called the cerebellum, which is badly damaged in A-T patients. Another project is searching for a drug treatment for A-T patients based on our recent understanding of the disease.

 

Publications

Kirshner, M., Galron, R., Frenkel, D., Mandelbaum, G., Shiloh, Y., Wang, Z.-Q., and Barzilai, A. (2012) Malfunctioning DNA damage response (DDR) leads to the degeneration of nigro-straiatal pathway in mouse brain. J. Mol. Neurosci. 46:554-68.

 

Tzur-Gilat, A., Ziv, Y., Dusart, I., Mittelman, L., Barzilai, A., and Shiloh, Y. (2013) Studying the cerebellar DNA damage response in the tissue culture dish. Mech. Ageing Dev. 134:496-505.

 

Rasmussen LJ, Shiloh Y, Bergersen LH, Sander M, Bohr VA, Tønjum T. (2013) DNA damage response, bioenergetics, and neurological disease: the challenge of maintaining brain health in an aging human population. Mech Ageing Dev. 134:427-33

 

Rashi-Elkeles S, Warnatz HJ, Elkon R, Kupershtein A, Chobod Y, Paz A, Amstislavskiy V, Sultan M, Safer H, Nietfeld W, Lehrach H, Shamir R, Yaspo ML, Shiloh Y. (2014) Parallel profiling of the transcriptome, cistrome, and epigenome in the cellular response to ionizing radiation. Sci Signal. M7(325):rs3.

 

Meir, M., Galanty, Y., Kashani, L., Blank, M., Khosravi, R., Fernández-Ávila, M.J., Cruz-Garcia, A., Star, A., Shochat, L., Thomas, Y., Garrett, L.J., Chamovitz, D.A., Bodine, D.M., Kurz, T., Huertas, P., Ziv, Y., and Shiloh, Y. (2015) The COP9 signalosome is vital for timely repair of DNA double-strand breaks. Nucleic Acids Res. 43: 4517-4530.

 

 

Reviews

Bensimon, A., Aebersold, R., and Shiloh, Y. (2011) Beyond ATM: the proteinkinase landscape of the DNA damage response. FEBS Letters 585:1625-1639.

 

Shiloh, Y., Shema, E., Moyal, L., and Oren, M., (2011) RNF20-RNF40: a ubiquitin-driven link between gene expression and the DNA damage response. FEBS Letters, 585:2795-2802.

 

Shiloh, Y., and Ziv, Y. The ATM protein: the importance of being active (Commentary) J. Cell Biol. 198:273-275.

 

Shiloh, Y., and Ziv, Y. (2013) The ATM protein: regulating the DNA damage response, and more. Nature Rev. Mol. Cell Biol. 14:197-210.

 

Shiloh, Y. (2014) ATM: expanding roles as a chief guardian of genome stability. Exp. Cell Res. 329:154- 161. 

 

Ribezzo, F., Shiloh, Y., and Schumacher, B. (2016) Systemic DNA damage responses in aging= and diseases. Seminars in Cancer Biology 38:26-35.

 

Tal, E. and Shiloh, Y. (2016) Monitoring the ATMmediated DNA damage response in the cerebellum using organotypic cultures. Methods in Molecular Biology (in press).

 

Barzilai, A., Schumacher, B., and Shiloh, Y. (2016) Genome instability: linking ageing and brain degeneration. Mechanisms of Ageing and Development (in press).

 

Shiloh, Y., and Lederman, H. (2016) Ataxiatelangiectasia (A-T): an emerging dimension of Sackler Faculty of Medicine Research 2016 36 Cancer and Molecular Therapies premature ageing. Ageing Research Reviews (in press).

 

 

Patents

  • USA Patent No. 5,756,288, "Ataxia-Telangiectasia Gene"
  • USA Patent No. 5,777,093, "cDNAs Associated with Ataxia-Telangiectasia"
  • USA Patent No. 5,728,807, "Mutated proteins Associated with Ataxia-Telangiectasia" 
  • USA Patents No. 5,858,661 and 2,265,158 B1, "Ataxia-Telangiectasia Gene and its Genomic Organization "

 

 

Grants

  • 2014 – 2021 Israel Cancer Research Fund (ICRF Professorship)
  • 2014 – 2017 Israel Science Foundation (Joint ISFNSFC Program with the National Natural Science Foundation of China)
  • 2015 – 2020 The A-T Children’s Project
  • 2016 – 2017 The A-T Ease Foundation
  • 2016- 2020 US-Israel Binational Science Foundation
  • 2015 – 2017 Dr. Miriam and Sheldon G. Adelson Medical Research Foundation

 

אוניברסיטת תל-אביב, ת.ד. 39040, תל-אביב 6997801
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