Lead Story

We generated a strain of the intracellular bacteria, Shigella that preferentially infects Glioblastoma brain tumor cells (https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1229747/full).

These microscopy images are of glioblastoma (GBM) cells incubated with GBM-infecting shigella. F-actin indicates the cell boundary to demonstrate that the bacteria (rendered green) are inside the cell. We envision these bacteria as a drug delivery platform to eradicate any GBM tumor missed during surgery.

We discovered that altering the beat frequency of ependymal cilia enhances the accumulation of chemotherapy in the brain to dramatically improve treatment of glioblastomas (J Control Release. 2023 Oct 19:S0168-3659(23)00674-0.).

Graph on the left depicts the survival of mice bearing orthotopic brain tumors treated with an ependymal cilia inhibitor (lidocaine) and temozolomide, the standard chemotherapy used for treating brain tumors. Administering with both cilia inhibitor and temozolomide results in 100% of animals surviving tumor free. Representative images of brain slices from mice treated with different combinations of cilia inhibitor and temozolomide are shown on the right. Tumor region is labeled with a “T”.

We recently described using neural extra-cellular matrix (ECM) binding Variable Lymphocyte Receptors (VLRs) to target regions of Blood-Brain Barrier (BBB) disruption induced by neuropathologies including glioblastoma (Sci Adv. 2019 May 15;5(5):eaau4245).

We have developed Express Protein Ligation (EPL) protocols to facilitate modification of antibodies specifically at the c-terminus with a variety of chemical handles (Bioconjug Chem. 2018 May 16;29(5):1605-1613).

Schematic of EPL protocol on the left and microscopy images EPL modified antibodies accumulating live mammalian cells on the right

We have developed a fully synthetic, targeted peptide-based immunotherapy for treating Non-small Cell Lung Cancer (Mol Ther. 2015 Jun;23(6):1092-1102).