Research Highlight


Immunofluorescent image of ST antigen expression (green) overlaid on the nucleus (blue) of IMR90 cells. Source: DFCI

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

Polyomaviruses are a non-enveloped double stranded DNA based virus that exists in nearly the entire population in various forms. Generally, the polyomavirus genome encodes for two transcriptional proteins, small T and large T in the early region, which are formed from alternative splicing of the region, as well as structural capsid proteins. Merkel cell polyomavirus was discovered using pyrosequencing in Merkel cell carcinoma. It was discovered that this viral genome was integrated into the genome of the cancer. Furthermore, mutations and deletions in the viral genome that inhibit viral DNA replication were discovered. It has been known that cancerous cells require an influx of nutrients and biosynthetic activity in order to duplicate all the cellular components in a rapid rate. Thus metabolic rates of cancerous cells are fundamentally higher than those in normal cells. Tumor cells are also shown to exhibit a phenotype known as the Warburg effect, where the energy necessary for replication is mostly produced by a high rate of glycolysis and lactic acid fermentation in the cytoplasm rather than the oxidation of pyruvate. However, excessive use of glycolysis produces excessive amounts of lactate, which in turn reduces the pH of the surrounding environment. Recently, it has been shown that certain cells are able to uptake the lactate and use it to fuel respiration through high prevalence of the MCT1 transporter. It has also been shown that inhibiting the MCT1 transporter in cells that are suspected to intake lactate environment has been shown to exhibit apoptosis rather than glucose fueled respiration. High levels of internal lactate have been characteristically observed in Merkel cell carcinoma lines. It is suspected that one of the T antigens of the virus is able to modulate the metabolic process of a normal Merkel cell in order to induce transformation. This hypothesis will be tested in IMR90 cells that inducibly express the small T antigen in order to observe whether there is a difference in lactate concentration inside and outside the cell. The effect of α-cyano-4-hydroxycinnamate (CHC,) an MCT1 transporter inhibitor, will also be investigated. There is great promise in the medicinal properties of MCT1 transporter inhibition. It is necessary to examine its inhibition in order to explore the possibilities of alternative cancer treatment therapies.

 

 


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:

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

miRNA analysis of up regulated miRNA-645 and miRNA-1290 in mouse orthotropic 4t1 model of metastatic breast cancer

Combined Cisplatin and Olaparib nanoparticles for ovarian cancer therapy

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

Identification of novel therapeutic targets of the Notch1 signaling pathway

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

The Assessment and Comparison of Ferumoxtran as Contrast Imaging Agent in Patients with Pancreatic Cancers.

Small T Antigen Effect on Mitotic Proteins B-Myb and FOXM1

Quantification of SPION accumulation in tumors using positive-contrast MRI

Pharmacokinetic analysis of changes in temozolomide distribution after antiangiogenic treatment of glioblastoma

Longitudinal assessment of tumor heterogeneity during immunotherapy for metastatic melanoma

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

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

Quantitative Multimodal Imaging of Tumor Response to Radiation

Digital diffraction diagnostics for lymphoma and HPV

Identifying genomic and compound dependencies in undifferentiated sarcomas

Targeting WASp using Wiskostatin-gold nanoparticles

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

Assessment of neoadjuvant therapy-induced atherosclerotic changes using ferumoxytol-enhanced MR imaging

Uptake and localization of nanoparticles in prostate and lung cancer cells as a function of time and nanoparticle type


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