Susana Gonzalo, PhD

Bio

susana-gonzaloI received my B.S. in Biology/Biochemistry from Universidad Complutense de Madrid, and my Ph.D. from Washington University School of Medicine (WUSM), studying the role of palmitoylation of neuronal proteins in their localization and function. I did postdoctoral research in the laboratory of Doug Dean at WUSM, studying the retinoblastoma family of tumor suppressors. A NSF International Postdoctoral Fellowship allowed me to join Maria Blasco’s team at the CNIO (leader in the telomere field) to define the role of retinoblastoma proteins in telomere biology and chromatin structure.  Our findings opened a new research area known as “telomere epigenetics”. In 2006, I joined WUSM as faculty of the Radiation Oncology Department, where I developed a research program focused on understanding how alterations in nuclear architecture impact genome stability. In 2012, I began my journey at the Biochemistry and Molecular Biology Department at SLU. These years as group leader, with the help of a great team of students, postdocs, assistants, and collaborators, have allowed me to establish a footprint in my field. In particular, our studies have led the way to unveil critical roles for structural nuclear proteins -lamins- as “genome caretakers”, and to identify molecular mechanisms underlying the pathophysiology of laminopathies, which we are targeting with therapeutic purposes.

Research

Our research is focused in three main areas: (1) Uncovering essential roles for lamins maintaining DNA repair, DNA replication, and telomere structure, length, and function; (2) Identifying new mechanisms underlying Hutchinson Gilford Progeria Syndrome (HGPS) pathology, a devastating premature aging disease; and (3) Defining the relationship between lamins loss and oncogenic mechanisms, focusing on cancers with the poorest prognosis such as BRCA-mutated and triple negative breast cancers. Among our discoveries, I highlight as most significant, the high similarities that we find in molecular mechanisms of disease in HGPS and aggressive breast cancers, including deficiencies in DNA repair/replication and vitamin D signaling. Importantly, we find that the hormonal form of vitamin D greatly improves disease phenotypes in cells from breast cancer and HGPS patients. These findings, explained in detail in a video (https://www.youtube.com/watch?v=TjQepjq23EQ) in our webpage, place vitamin D biology in the vanguard of aging and cancer.

Lab website: https://biochem.slu.edu/faculty/gonzalo/

Recent publications

Coll-Bonfill N, Cancado de Faria R, Bhoopatiraju S and Gonzalo SCalcitriol Prevents RAD51 Loss and cGAS-STING-IFN Response Triggered by Progerin. (2020) Proteomics. 20, e1800406.

Maynard S, Keijzers G, Akbari M, Ezra MB, Hall A, Morevati M, Scheibye-Knudsen M, Gonzalo S, Bartek J and Bohr VA. Lamin A/C promotes DNA base excision repair. (2019) Nucleic Acids Res. 47, 11709-11728.

Kreienkamp R, Billon C, Bedia-Diaz G, Albert CJ, Toth Z, Butler AA, McBride-Gagyi S, Ford DA, Baldan A, Burris TP and Gonzalo SDoubled lifespan and patient-like pathologies in progeria mice fed high-fat diet. (2019) Aging Cell. 18, e12852.

Kreienkamp R, Graziano S, Coll-Bonfill N, Bedia-Diaz G, Cybulla E, Vindigni A, Dorsett D, Kubben N, Batista LFZ and Gonzalo SA Cell-Intrinsic Interferon-like Response Links Replication Stress to Cellular Aging Caused by Progerin. (2018) Cell Rep. 22, 2006-2015.

Graziano S, Johnston R, Deng O, Zhang J and Gonzalo SVitamin D/vitamin D receptor axis regulates DNA repair during oncogene-induced senescence. (2016) Oncogene. 35, 5362-5376.

Kreienkamp R, Croke M, Neumann MA, Bedia-Diaz G, Graziano S, Dusso A, Dorsett D, Carlberg C and Gonzalo SVitamin D receptor signaling improves Hutchinson-Gilford progeria syndrome cellular phenotypes. (2016) Oncotarget. 7, 30018-31.

Bronshtein I, Kepten E, Kanter I, Berezin S, Lindner M, Redwood AB, Mai S, Gonzalo S, Foisner R, Shav-Tal Y and Garini Y. Loss of lamin A function increases chromatin dynamics in the nuclear interior. (2015) Nat Commun. 6, 8044.

Grotsky DA, Gonzalez-Suarez I, Novell A, Neumann MA, Yaddanapudi SC, Croke M, Martinez-Alonso M, Redwood AB, Ortega-Martinez S, Feng Z, Lerma E, Ramon y Cajal T, Zhang J, Matias-Guiu X, Dusso A and Gonzalo SBRCA1 loss activates cathepsin L-mediated degradation of 53BP1 in breast cancer cells. (2013) J Cell Biol. 200, 187-202.

Gonzalez-Suarez I, Redwood AB, Grotsky DA, Neumann MA, Cheng EH, Stewart CL, Dusso A and Gonzalo SA new pathway that regulates 53BP1 stability implicates cathepsin L and vitamin D in DNA repair. (2011) EMBO J. 30, 3383-96.

Gonzalez-Suarez I, Redwood AB, Perkins SM, Vermolen B, Lichtensztejin D, Grotsky DA, Morgado-Palacin L, Gapud EJ, Sleckman BP, Sullivan T, Sage J, Stewart CL, Mai S and Gonzalo SNovel roles for A-type lamins in telomere biology and the DNA damage response pathway. (2009) EMBO J. 28, 2414-27.