Research Highlight
Imaging the nuclear and cytosolic fluorescence of green (GFP) and red (RFP) fluorescent protein-bound kinases in murine ovarian cancer cells can yield quantitative data on pathway activity. The hoechst image allows identification of the cells' nuclei, while GFP and RFP label the mitogen-activated protein kinases ERK and JNK. The presence of nuclear localization sequences on the fluorophore-bound proteins allows for measurement of kinase activity by comparing nuclear and cytosolic fluorescence. In this way, pathway function can be compared under varying experimental conditions, like the addition of a kinase inhibitor. This data can be used to investigate the effectiveness of nanoparticle formulations in vitro.
Tyrosine kinase inhibitors such as sunitinib, foretinib, and crizotinib comprise a significant class of cancer-fighting compounds. These molecules function by binding to receptor tyrosine kinases (RTKs) such as MET, VEGFR, and MERTK. This disables phosphorylation in pathways that can lead to oncogenic or inflammatory responses in cancer cells, such as the MAPK pathways ERK and JNK. Despite promising indications, kinase inhibitors have shown results that are highly variable from patient to patient. These discrepancies may be partly due to problems in drug delivery, arising from these molecules’ categorical hydrophobicity. One potential solution is the encapsulation of kinase inhibitors in amphiphilic nanoparticles. Development of a nanoparticle-packaging platform for these molecules would provide the scientific community with an adaptable mechanism for improving drug delivery. Furthermore, nanoparticles can be customized to include tumor or immune targeting moieties, which may enable their use to target specific pathways in immune-tumor interactions. My work will involve identification of successful nano-encapsulation strategies for different kinase inhibitors. Subsequently, nanoparticle performance will be monitored in vitro and vivo. Eventually, the targeting of nanoparticles to interfere with tumor-immune crosstalk will explore the feasibility of employing nanoparticles in immuno-oncology.
Trainee Research
CaNCURE provides trainees with a 6-month hands-on research experience and one-on-one mentoring by leading researchers in cancer nanomedicine. Projects performed by current and past participants include:
miRNA analysis in mouse model of metastatic breast cancer. (Proj 2) The inhibition of PD-L1 on a Pan02 cell line w/ siRNA-nanodrug & gemcitabine treatment
Identification of novel therapeutic targets of the Notch1 signaling pathway
Targeting WASp using Wiskostatin-gold nanoparticles
Combined delivery of targeted liposomal chemotherapeutics and photodynamic therapy to treat pancreatic cancer
Erythropoietin improves antitumor immune response through reversal of the hypoxic tumor microenvironment
Combined Cisplatin and Olaparib nanoparticles for ovarian cancer therapy
Use of a Triblock Copolymer Hydrogel for Controlled Release of Cisplatin and BMN-673
Development of PSMA-targeting nanoparticles for positron emitting tomography imaging in prostate cancer using animal models
Co-delivery of antibiotics and topoisomerase inhibitors to overcome chemoresistance
Analysis of DREAM and E2F1 Competition for Cell Cycle Promoters during G1.
Quantitative Multimodal Imaging of Tumor Response to Radiation
In vivo imaging of targeted drug delivery to HER2 positive cancer cells
Co-delivery of protective substrate and chemotherapy drugs via lipid Bilayer Mesoporous Silica Nanoparticles
Nano-plasmonic exosome (nPLEX) assays for exosome analysis and antibody validation
Inhibiting DNA repair after nanoparticle-amplified radiation therapy
Delivery of Titanium Dioxide Nanoparticles via Biodegradable PLGA Dissolving Microneedles for Sustainable Release
Small T Antigen Effect on Mitotic Proteins B-Myb and FOXM1
Identifying genomic and compound dependencies in undifferentiated sarcomas
Software with built-in neuroanatomy atlas provides insight into cancer treatment
The Assessment and Comparison of Ferumoxtran as Contrast Imaging Agent in Patients with Pancreatic Cancers.
Uptake and localization of nanoparticles in prostate and lung cancer cells as a function of time and nanoparticle type
Digital diffraction diagnostics for lymphoma and HPV
Assessing the reproducibility of MRI-based brain tumor measurements between both observers and MRI vendors
MCT1 Transporter Inhibition of IMR90 Cells Expressing Inducible Merkel Cell Carcinoma Small T Antigen
Development of a novel nanogel for non-invasive transdermal delivery of cancer vaccines using hyaluronic acid
Trainee e-portfolios
While on co-op, trainees document their research in an e-portfolio. This gives trainees the opportunity to provide regular updates on their research progress, reflect on training they are receiving, and explain how their research fits within the field of cancer nanomedicine. These research e-portfolios can be accessed through individual trainee profiles. The complete collection may be found here.
Check out this month’s featured e-portfolios by Rachel Fontana and Jordan Harris!
Presentation at CaNCURE Nanomedicine Day
At the completion of their co-op, trainees are provided with the opportunity to present their research to a wider audience. In our 1st annual CaNCURE Nanomedicine Day, trainees prepared interactive, digital posters to display on electronic poster boards. Over 100 faculty, students, and researchers attended our first event!
Check out the news article and congrats to all the poster winners!
Jordan Harris: Most Innovative Cancer Research Award
Jeremy Thong: Best Undergraduate Research Poster Award
Craig Pille: Most Promising Translational Research Award
Bryan Kynnap: Most Promising Basic Science Award
Jordan Harris: Top Chemical Engineering Poster Award
