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Susana Gonzalo, Ph.D.

Associate Professor, Department of Biochemistry & Molecular Biology

Saint Louis University School of Medicine

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Our long-term research interest is the understanding of molecular mechanisms that contribute to the genomic instability that drives aging and cancer, with the ultimate goal of targeting these mechanisms therapeutically. The spatial and temporal organization of the genome has emerged as an additional level of regulation of genome function and integrity. Nuclear lamins orchestrate genome organization, forming a scaffold for tethering chromatin and protein complexes regulating many nuclear functions.

Lamins dysfunction impacts nuclear architecture, chromatin structure, as well as DNA transcription, replication and repair. These data, and the association of lamins dysfunction with dozens of degenerative disorders, premature aging, and cancer, provide evidence for these proteins operating as "caretakers of the genome."

Our research focuses on identifying mechanisms whereby lamins regulate genome stability and function, as these mechanisms are key to identifing therapies that ameliorate the progression of laminopathies in patients. In addition, we are interested in the genomic instability that drives breast cancers with the poorest prognosis, such as BRCA-mutated and triple negative (TNBC). Intriguingly, we found similar alterations in cells from these aggressive cancers and in cells from laminopathies, including deficiencies in DNA repair and in the vitamin D/vitamin D receptor (VDR) axis.

We have shown that calcitriol, the most bioactive vitamin D metabolite, ameliorates genomic instability phenotypes in breast cancer cells and in lamins-deficient cells. These important findings suggest that targeting the vitamin D/VDR axis could have beneficial effects in subsets of TNBC patients, as well as in some laminopathy patients.

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Copyright 2009 Washington University School of Medicine Department Radiation Oncology.