Research
 
A key feature of any living organism is to preserve its genome integrity. To this end, cells use specialized proteins that survey the genome to detect and repair any lesion in the DNA. These vital processes however, must be kept in check at naturally occurring DNA breaks; the ends of linear chromosomes. For this reason, all eukaryotic cells have telomeres, essential nucleoprotein structures that cap chromosome ends. Perturbation of telomere function occurs frequently in human pathologies such as cancer and aging. In these pathologies telomere DNA is progressively lost and a DNA damage response is initiated at chromosome ends. Our lab focuses on two fundamental aspects of telomere biology: the mechanism by which functional telomeres prevent DNA damage activation and the in vivo consequences of telomere dysfunction.

We take advantage of mouse genetics to probe the role of specific telomere-associated proteins in the suppression of a DNA damage response. Current work is focused towards the understanding of the mechanisms employed by these proteins to suppress the DNA damage response. Additional work in the lab is aimed towards the discovery of novel DNA damage factors involved in the DNA damage response initiated at dysfunctional telomeres. High throughput screenings and a candidate approach are being developed in the lab to take advantage of dysfunctional telomeres as unique tools to study the DNA damage response pathways in mammalian cells.
A complementary study in our lab is focused on the in vivo consequences of telomere dysfunction. Telomere length homeostasis plays a critical role for cellular and organism survival. However, in humans this process is inefficient and progressive telomere shortening is observed in tissues with high cellular turnover. In the lab we probe the role of telomere shortening in aging and tumor onset using mouse models that recapitulate telomere dysfunction in stem cells and other cellular compartments.



News and Press Releases:


http://www.scripps.edu/news/press/2016/20160526lazzerini.htmlhttp://www.scripps.edu/news/press/2016/20160526lazzerini.htmlhttps://www.scripps.edu/newsandviews/e_20130211/denchi.html