Ph.D., Washington University School of Medicine
Research Interests
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. Our broad research interests are to understand how alterations of nuclear architecture, chromatin structure, and genome stability contribute to the processes of aging and cancer. Our studies revealed that the structural nuclear proteins A-type lamins play a key role in the maintenance of telomere structure, length and function, as well as mechanisms of DNA double-strand break repair. Specifically, loss of A-type lamins increases the levels of the protease cathepsin L and its entry into the nucleus, which in turn leads to degradation of proteins with important roles in cell cycle regulation -Rb family members- and DNA repair -53BP1-. Loss of A-type lamins also leads to repression of BRCA1 and RAD51 genes, critical factors in homologous recombination. Interestingly, inhibition of cathepsin L activity with vitamin D or specific inhibitors rescues some of the phenotypes of lamins-deficient cells, providing new therapeutic possibilities. Most recently, we found that these novel pathways are also activated in BRCA1-deficient cells and subsets of breast cancer patients. Our current work aims to characterize in detail how these pathways contribute to the pathophysiology of cancer, aging, and laminopathies with the ultimate goal of using them as potential biomarkers for diagnosis, prognosis, and customization of treatment.
Recent Publications
  • Loss of lamin A function increases chromatin dynamics in the nuclear interior.
    Bronshtein I, Kepten E, et al. Nat Commun. (2015) 6:8044-8052.
  • DNA repair defects and genome instability in Hutchinson-Gilford Progeria Syndrome.
    Gonzalo S, Kreienkamp R. Curr Opin Cell Biol. (2015) 34:75-83.
  • DNA damage and lamins.
    Gonzalo S. Adv Exp Med Biol. (2014) 773:377-399.
  • Lamin A Δexon9 mutation leads to telomere and chromatin defects but not genomic instability.
    Das A, Grotsky DA, et al. Nucleus. (2013) 4(5):410-419.
  • Differences in 53BP1 and BRCA1 regulation between cycling and non-cycling cells.
    Croke M, Neumann MA, et al. Cell Cycle. (2013) 12(23):3629-39.
  • Novel roles of 1α,25(OH)2D3 on DNA repair provide new strategies for breast cancer treatment.
    Gonzalo S. J Steroid Biochem Mol Biol. (2013) 144PA:59-64.
  • The two faces of DNA repair: disease and therapy.
    Vindigni A, Gonzalo S. Mo Med. (2013) 110(4):314-319.
  • BRCA1 loss activates cathepsin L-mediated degradation of 53BP1 in breast cancer cells.
    Grotsky DA, Gonzalez-Suarez I, et al. J Cell Biol. (2013) 200(2):187-202.