Research Highlight


Murine fallopian tube cells grown in vitro as a spheroid that was originally isolated from the BRCA1 (fl/+) p53 (fl/mut) PTEN (fl/fl) murine cohort. The micrograph reveals red fluorescence from the presence of mCherry, indicating a successful transfection of our mCherry/luc plasmid (Image taken at 40X). Source: Unpublished original research, Morgan Krush, Dinulescu Laboratory.

Optimizing murine cells for in vitro modeling of high-grade serous ovarian cancer

High-grade serous ovarian carcinoma (HGSC) is known to be the most aggressive and lethal subtype of ovarian cancer. Recent research indicates that improved, well-characterized HGSC cell lines are needed in order to perform more effective in vitro pre-clinical studies that accurately represent HGSC. The culturing of high-grade serous murine/human ovarian cancer cells from tumors, fallopian tissues or ascites has been challenging, as the establishment of primary lines most often requires the use of specialized medias and immortalization of cells. These techniques frequently lead to alterations in the cell pathways that may not be representative of the actual tumor. Our study aims to highlight a new method of generating novel HGSC cell lines from fallopian tube secretory cells, which have recently been acknowledged in literature as a significant initiation or origin site for HGSC. We will be isolating fallopian tube cells directly from a genetically engineered murine model generated by the Dinulescu laboratory. Using this model, we plan to generate a normal murine FTSEC cell line using cells that harbor conditional Brca;TP53;PTEN mutational signatures which closely recapitulate those of human HGSC. We will then treat the normal cells with doxycycline in order to induce the Brca;TP53;PTEN mutations, establishing a cancerous subset of cells. Using these cells directly derived from the mouse model and induced using doxycycline, we hypothesize that we will be able to accurately mimic human HGSC in vitro by engrafting the cancerous cells into immunodeficient mice intraperitoneally. We hypothesize that these cells will develop in the immunocompromised mice and model HGSC tumor growth in vivo. We will confirm the development of the transplanted cells using luciferase imaging in living mice and through necropsy of euthanized mice. These cells will serve as a unique tool for future research into understanding “ovarian” cancer etiology, oncogenic pathway aberrations, and allow reliable in vitro trials for novel chemotherapeutics such as nanoparticles, before performing in vivo studies.

 

 


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:

Identification of novel therapeutic targets of the Notch1 signaling pathway

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

Optimization of macrophage-targeted nanoparticles for positron emission tomography imaging in cancer

Use of a Triblock Copolymer Hydrogel for Controlled Release of Cisplatin and BMN-673

Development of a novel nanogel for non-invasive transdermal delivery of cancer vaccines using hyaluronic acid

Protein-encapsulated nanoparticles for oral delivery of anti-mitotic agents in prostate cancer

Nanoencapsulation of tyrosine kinase inhibitors and their effects on pathway inhibition

Targeting CXCR4/SDF-1a using phytochemicals to inhibit progression and metastasis of pancreatic cancer

Erythropoietin improves antitumor immune response through reversal of the hypoxic tumor microenvironment

Biological mechanisms of gold nanoparticle-enhanced radiation therapy of prostate cancer

Targeting WASp using Wiskostatin-gold nanoparticles

T1-weighted imaging of primary pancreatic adenocarcinoma using magnetic ferumoxytol nanoparticles

MCT1 Transporter Inhibition of IMR90 Cells Expressing Inducible Merkel Cell Carcinoma Small T Antigen

Radiation enhancement in cancer cells using gold and gadolinium nanoparticles

Nano-plasmonic exosome (nPLEX) assays for exosome analysis and antibody validation

Online monitoring and image-guided treatment of chemoresistant micrometastases

Capture of circulating tumor DNA through the use of biotinylated poly-lysine affixed to gold nanoparticles

Injectable thermogelling cisplatin-loaded hydrogels for combined chemo-radiation therapy in cervical cancer

Optimizing murine cells for in vitro modeling of high-grade serous ovarian cancer

Quantitative Multimodal Imaging of Tumor Response to Radiation

Co-delivery of protective substrate and chemotherapy drugs via lipid Bilayer Mesoporous Silica Nanoparticles

Software with built-in neuroanatomy atlas provides insight into cancer treatment

Digital diffraction diagnostics for lymphoma and HPV

Mechanistic and modeling studies of lipid nanoemulsions impact on oral lapatinib absorption

Iron-chelating PEG-like nanoprobes as therapeutic and 89Zr/PET imaging agents


Soleil Doggett (Biology, '16) talks to her fellow peers about her research on oxygenating tumors to stimulate the anti-tumor immune response.

 


Trainee e-portfolios

Photo credit: Tom Kates Photography

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