The human genome is organized into different levels of complexity. Packaging of DNA into different chromatin states and 3D nuclear organization of the genome are emerging as additional levels of regulation of genome function and integrity.
Our broad research interests are to understand how alterations of nuclear architecture contribute to the genomic instability that drives aging and cancer processes. Our studies are revealing essential roles for the structural nuclear protein A-type lamins in DNA repair, DNA replication, and telomere homeostasis, as well as in genome compartmentalization and mobility within the nuclear space. These findings, and the association of lamins dysfunction with degenerative disorders, premature aging, and cancer, provide evidence for lamins operating as “caretakers of the genome.”
We are currently focusing on three areas of research:
Intriguingly, our studies in cancers with poor prognosis, such as BRCA-mutated and triple negative breast cancers (TNBC), show striking similarities with cellular phenotypes of HGPS patients, including deficiencies in DNA repair/replication and in vitamin D receptor (VDR) signaling. Importantly, we discovered that calcitriol, the most bioactive vitamin D metabolite, greatly improves a variety of phenotypes in cells from breast cancer and HGPS patients.
Our long-term goal is to characterize how these pathways contribute to disease in cells in vitro and in animal models in vivo, as well as their potential as targets for treatment of lamins-related diseases.