Chemotherapy-Induced Peripheral Neuropathy (CIPN)

Chemotherapy agents used to treat cancer may damage the nervous system. Peripheral neuropathy is a common dose-limiting side effect.

We have studied the mechanism of cisplatin neurotoxicity for a number of years. Cisplatin binds nuclear and mitochondrial DNA (mtDNA) in cancer cells and rat dorsal root ganglion (DRG) neurons inducing DNA damage and apoptosis.

Our studies found mitochondrial DNA binding inhibits mtDNA replication and mtRNA transcription leading to mitochondrial disassembly. Our lab has developed a novel model of cisplatin-induced neurotoxicity in Drosophila melanogaster using survival and behavioral assays.

The drosophila model system provides a powerful tool to study basic cellular mechanisms using genetic approaches. We are using genetic epidemiology, high-density genome sequencing and epigenetic approaches to study CIPN in patients and to test hypotheses in model systems.

Project Personnel

  • Andreas S. Beutler, M.D.
  • Cassandra Johnson
  • Amit A. Kulkarni, MBBS
  • Jewel L. Podratz
  • Nathan P. Staff, M.D., Ph.D.
  • Lauren E. Ta, D.D.S., Ph.D.
  • Eugenia Trushina, Ph.D.