Giant Obscurins: Novel Tumor and Metastasis Suppressors in Breast Epithelial Cells

Obscurins, encoded by the single OBSCN gene, are giant (720-860 kDa) cytoskeletal proteins with scaffolding and regulatory roles. The OBSCN gene is highly mutated and/or epigenetically modified in multiple types of cancer, including breast cancer. Consistent with this, Kaplan-Meier-Plotter data sets have indicated that low OBSCN levels correlate with significantly reduced survival and relapse-free survival in breast cancer patients. Our research focuses on interrogating the impact of obscurins’ loss from normal breast epithelial cells, the delineation of the molecular alterations that take place downstream of obscurins’ loss, and the development of novel and effective ways to restore obscurin expression and/or functionality.

Aikaterini Kontrogianni-Konstantopoulos research focuses on the elucidation of the roles of cytoskeletal and membrane-associated proteins as structural and signaling mediators. Using the muscle and epithelial cell as model systems, my laboratory has pioneered the molecular and functional characterization of the obscurin subfamily and its binding partner Myosin Binding Protein-C slow in health and disease. In 2007, she joined the Department of Biochemistry and Molecular Biology at the University of Maryland School of Medicine as Assistant Professor in the tenure track. Using the muscle and epithelial cell as model systems, her laboratory has pioneered the molecular and functional characterization of major cytoskeletal and membrane-associated proteins as structural and signaling mediators in health and disease.

From Polymers to DNA: Self-Assembled Nanomaterials that Target Cancer

Self-assembly of polymers or biological molecules is an attractive method for engineering supramolecular biomaterials for biomedical applications. Kokkoli’s research focuses on the design and characterization of novel amphiphilic molecules that have the tendency to self-assemble spontaneously in different structures in water. She will discuss two examples, the design and characterization of a new thermosensitive and biodegradable polymer that can be used for the local delivery of targeted nanoparticles or different therapeutics, and the assembly of ssDNA-amphiphiles into nanotubes used to target glioblastoma multiforme (GBM), in vitro and in vivo in an orthotopic mouse model of GBM, in the absence of any targeting moiety.

Efie Kokkoli, a targeted drug delivery specialist, is a professor in the Chemical and Biomolecular Department at the Whiting School of Engineering. Her research focuses on the areas of DNA nanotechnology, multi-targeted gene and drug delivery, and the design of biopolymers and responsive hydrogels. With the goal of directing nanoparticles capable of carrying cancer drugs to tumor sites while sparing non-cancerous areas, her group concentrates on designing biomaterials ranging from polymeric nanoparticles to DNA nanotubes that respond best under certain conditions, like temperature or pH, and have specificity for cancer cells.