Surgery remains the mainstay of treatment options for patients with glioblastoma. However, these tumors diffusely infiltrate the normal brain and are resistant to adjuvant therapies such as radiation and chemotherapy. In collaboration with Shawn Hingtgen and Kristie Ainslie in the UNC Eshelman School of Pharmacy, we design novel mouse models of post-surgical glioblastoma to aid in the development of therapies targeted to post-surgical disease, including drug-eluting depots and cellular therapies that seek out and home to invasive cancer cells.

Project summary

The Miller Lab is focused on development of novel genetically-engineered mouse (GEM) models of post-surgical glioblastoma that diffusely invade the normal brains of mice with an intact immune system.

The Hingtgen Lab is focused on development of novel cellular delivery vehicles, particularly induced neural stem cells, that can seek out and home to invasive cancer cells.

The Ainslie Lab is focused on development of novel polymeric drug delivery vehicles, particularly those using acetalated dextran scaffolds.


References

  1. Okolie O, Irvin DM, Bago JR, Sheets K, Satterlee A, Carey-Ewend AG, Lettry V, Dimitru R, Elton S, Ewend MG, Miller CR, Hingtgen SD.  Intra-cavity stem cell therapy inhibits tumor progression in a novel murine model of medulloblastoma surgical resection.  PLoS One.  13(7):e0198596 Jul 2018.  PMID: 29990322 PMCID: PMC6038981
  2. Graham-Gurysh EG, Moore KM, Satterlee AB, Sheets KT, Lin FC, Bachelder EM, Miller CR, Hingtgen S, Ainslie KM. Sustained delivery of doxorubicin via acetalated dextran scaffold prevents glioblastoma recurrence after surgical resection.  Molecular Pharmaceutics.  15(3):1309-1318 Mar  PMID: 29342360  PMCID:  PMC5999333
  3. Bago JR, Okolie O, Dumitru R, Ewend MG, Parker JS, Vander Werff R, Underhill TM, Schmid RS, Miller CR, Hingtgen SD.  Tumor-homing cytotoxic human induced neural stem cells for cancer therapy.  Science Translational Medicine.  9(375):eaah6510 Feb 2017.  PMID: 28148846
  4. Okolie O, Bago JR, Schmid RS, Irvin DM, Bash RE, Miller CR*, Hingtgen SD*.  Reactive astrocytes potentiate tumor aggressiveness in murine glioma resection and recurrence model.  Neuro-oncology.  DOI: 10.1093/neuonc/now117 Jun 2016.  PMID: 27298311  *Co-senior authors
  5. Bago JR, Alfonso-Pecchio A, Okolie O, Dumitru R, Rinkenbaugh A, Baldwin AS, Miller CR, Magness ST, Hingtgen SD.  Therapeutically engineered induced neural stem cells are tumor-homing and inhibit progression of glioblastoma.  Nature Communications.  7:10593 Feb 2016.  PMID: 26830441 PMCID: PMC4740908