Prof. (Emeritus) Yosef Shiloh
Our lab investigates the human genetic disorder, ataxia-telangiectasia (A-T). A-T is a multisystem genome instability syndrome. It involves cerebellar degeneration that leads to progressive neuromotor dysfunction, immunodeficiency, chromosomal instability, cancer predisposition, and acute sensitivity to agents that induce double-strand breaks (DSBs) in the DNA, such as ionizing radiation (IR) and radiomimetic chemicals. The gene that is mutated in A-T, ATM, was identified in our lab in 1995, and since then the lab has been investigating the functions of its protein product, the ATM protein. ATM is a homeostatic, powerful and versatile protein kinase, which is involved in many cellular circuitries. Our lab investigates the various roles of ATM in cellular circuits. branches of the ATM-mediated DNA damage response. We strive to understand how the loss of ATM impacts the cellular and organismal phenotype. We are particularly interested in the most debilitating symptom observed in A-T patients – the cerebellar degeneration. The work is done using a variety of cellular and molecular biology techniques, systems biology tools and mouse models.
Behavioral Neuroscience
Cellular & Molecular Neuroscience
Neurodevelopment and Neurogenetic Research
- Shiloh, Y. (2020) The cerebellar degeneration in ataxia-telangiectasia: a case for genome instability. DNA Repair, doi: 10.1016/j.dnarep.2020.102950 .https://www.sciencedirect.com/science/article/pii/S1568786420301993?via%3Dihub
- Tal, E., Alfo, M., Zha, S., Barzilai, A., De Zeeuw, C., Ziv, Y., Shiloh, Y. (2018) Inactive Atm abrogates DSB repair in mouse cerebellum more than does Atm loss, without causing a neurological phenotype. DNA Repair, 72:10-17.https://www.sciencedirect.com/science/article/pii/S1568786418301678?via%3Dihub
- Tal, E. and Shiloh, Y. (2017) Monitoring the ATM-mediated DNA damage response in the cerebellum using organotypic cultures. Methods in Molecular Biology, 1599:419-430. https://link.springer.com/protocol/10.1007/978-1-4939-6955-5_30
- Tal, E. and Shiloh, Y. (2017) Monitoring the ATM-mediated DNA damage response in the cerebellum using organotypic cultures. Methods in Molecular Biology, 1599:419-430. https://link.springer.com/protocol/10.1007/978-1-4939-6955-5_30
- Kirshner, M., Galron, R., Frenkel, D., Mandelbaum, G., Shiloh, Y., Wang, Z.-Q., and Barzilai, A. (2011) Malfunctioning DNA damage response (DDR) leads to the degeneration of nigro-straiatal pathway in mouse brain. J. Mol. Neurosci., 46:554-68.https://link.springer.com/article/10.1007/s12031-011-9643-y
