Our lab investigates the role of genome instability in human morbidity and aging. Our interest in this field stems from our long-time investigation of 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. It is most vigorously activated by DSBs, and subsequently mobilizes a vast signaling network - the DNA damage response, by phosphorylating numerous targets in its various branches. ATM also enhances the responses to other DNA lesions or abnormal DNA structures by phosphorylating pertinent players. 

Our lab investigates the various branches of the ATM-mediated DNA damage response. We strive to understand how the loss of ATM impacts the cell’s complex response to genotoxic stresses, and to explain the most cardinal and debilitating symptom observed in A-T patients – the cerebellar degeneration. In parallel we are investigating the influence of genome instability on human morbidity in general and on the pace of aging. The work is done using a variety of cellular and molecular biology techniques, systems biology tools and mouse models.