Abstract

ABSTRACT :

G.V.Shivashankar: Mechanobiology Institute, National University of Singapore, Singapore & FIRC Institute of Molecular Oncology (IFOM), Milan, Italy

Abnormalities in nuclear and chromatin organization are hallmarks of many diseases including cancer. In this talk, I will describe our understanding of how the cellular microenvironment regulates nuclear morphology and, with it, the spatial organization of chromosomes and genes, resulting in cell type-specific genomic programs. I will also discuss the mechanical basis for maintaining nuclear homeostasis and how alterations in nuclear mechanotransduction pathways may result in various diseases. Finally, I will describe a digital nuclear mechanopathology platform that uses a multidisciplinary approach combining high resolution optical imaging, quantitative single-cell biology, machine learning and functional genomics. Collectively, our results based on nuclear mechanogenomic biomarkers are attractive not only for clinical applications such as cancer diagnosis, but also open new avenues for understanding the onset of cancer from a basic science perspective and for the development of therapeutic interventions.