Intracellular Molecular Delivery
Delivering molecules into cells can be made more precise with vectors that direct intracellular cargo to particular compartments. Our work has focused on mitochondrial targeting with a versatile peptide based vector that promotes efficient cellular uptake and strong mitochondrial localization.
Mitochondrial Drug Delivery
Using a peptide-based delivery vector that can carry reactive cargo into the mitochondria of live mammalian cells, we have delivered clinically-utilized anticancer drugs that typically act within the nucleus. This approach has elucidated a variety of interesting activities for mitochondrially-localized probes. We’ve also shown that mitochondrial delivery can detoxify antimicrobials within human cells by sequestering the drugs within this organelle.
Journal of the American Chemical Society, 2017, 139, 9455-9458.
Cell Chemical Biology, 2013, 20, 1323-1328.
ACS Chem. Biol., 2013, 8, 1389-1395.
"Maximizing the Therapeutic Window of an Antimicrobial Drug by Imparting Mitochondrial Sequestration in Human Cells "
J. Am. Chem. Soc., 2011, 133, 3260.
"Re-routing Chlorambucil to Mitochondria Enhances Potency and Combats Drug Resistance in Cancer Cells"
Cell Chemical Biology, 2011, 18, 445.
Mitochondrial Probes for the Discovery of New Organelle-Specific Activities
Mitochondrial probes also enable high-throughput screening for new organelle-specific factors. Using siRNA or CRISPR/Cas-based screening to knockdown factors in the nucleus that may function in mitochondria, synergistic effects can be detected in the presence of a mt-targeted probe. This type of analysis has allowed us to identify new factors that are key players in mitochondrial function.
Nature Chemical Biology, 2016, 12, 567-573.