Research Highlight


For project 1: Metastases of mice with human breast cancer cell 4t1 were imaged using IVIS optical imaging three weeks post cell injection. Luciferase was used as reporter to visualize the tumors. Luciferase is a gene expressed in tumor cells that interacts with a luciferin substrate that is injected into the mice prior to imaging. This interaction produces the light that is picked up by IVIS. Region of Interest (ROI) values designates the borders of the tumors

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

Project 1: In this project, three balb/c female mice were injected with a 4t1 cell line that promotes metastatic breast cancer. Mice were imaged every week starting three weeks post-injection using IVIS optical imaging. After about five weeks, the primary tumors were removed and their RNA was extracted. For the two weeks following primary tumor removal, the metastasis in these three mice were imaged and monitored. Upon sacrifice, metastasis was found in skull muscle, kidneys, periosteum, lungs, cardiac muscle, and lymph nodes. The RNA for these metastases were extracted using Qiagen's Rneasy Extraction Kit. Next, the RNA samples were sent to Exiqon for global microarray analysis to look for miRNA uniformly up regulated in the metastatic lesions relative to the primary tumors. MiR-645 and miR-1290 are expected to be commonly over expressed miRNAS. Project 2: For my second project, my lab focused on treating non-metastatic pancreatic cancer. We focused on the programmed dealth-ligand 1 (PD-L1). PD-L1 is a transmembrane protein that contributes to supressing the immune system by releasing a signal that inhibits the producting of CD-8+ T cells. Some studies have come to suspect that the upregulation of PD-L1 permits cancer to takeover the immune system.

 

 

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:

Codelivery of tumor suppressor mRNA and anti-cancer drug in cancer treatment

PDT and PIT with Chemotherapy for Treatment of 3D Ovarian Cancer Nodules Under Flow and Static Conditions

Enhanced delivery of camptothecin and doxorubicin conjugates with hyaluronic acid for the treatment of Glioblastoma using microbubble-mediated focused ultrasound

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

Evaluation of deep learning approaches in an integrated PET/MRI scanner to generate pelvis attenuation maps and characterize prostate cancer

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

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

Assessing sufficiency of the Tip60/p400 complex in inducing transcription of Merkel Cell Polyomavirus Small T antigen target genes.

Analysis of DREAM and E2F1 Competition for Cell Cycle Promoters during G1.

Metabolite Quantification from Cancer Tissues using Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging

Delivery of Titanium Dioxide Nanoparticles via Biodegradable PLGA Dissolving Microneedles for Sustainable Release

Triple-targeted Photonanomedicine: A Strategy to Treat Heterogeneous Tumors

Detection of low-level mutations in DNA obtained from cancer patients, using PCR and nano-PCR

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

Investigating the use of iron chelator deferoxamine (DFO)-bearing PEG-like nanoprobes as a multifunctional agent for cancer therapy and PET imaging

Digital diffraction diagnostics for lymphoma and HPV

Combined Cisplatin and Olaparib nanoparticles for ovarian cancer therapy

Co-delivery of antibiotics and topoisomerase inhibitors to overcome chemoresistance

Monocyte Subtype Determination by Labeling with Feraheme Nanoparticles

Surface-targeting, ligand-switching nanoparticles for mitochondrial drug delivery in prostate cancer

Identification of novel therapeutic targets of the Notch1 signaling pathway

Targeted Delivery of Talazoparib to Treat Non-Small Cell Lung Cancer

Quantification of SPION accumulation in tumors using positive-contrast MRI

Use of CT Texture Analysis for Characterization and Prognostication of Incidental Adnexal Lesions

RHAMM splicing in multiple myeloma (MM) and its implications for immunotherapy

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.

 

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.  For our June CaNCURE Nanomedicine Day, trainees prepare interactive, digital posters to display on electronic poster boards.  Over 100 faculty, students, and researchers attend this annual event!

Check out the news article about our first CaNCURE Day!

Trainee Publications

Our Trainees have published 22 peer-reviewed since January 2015.  A full list of Trainee publications is found below.

  1. Patrick Sheedy, Zdravka Medarova. The fundamental role of miR-10b in metastatic cancer. Am J Cancer Res 2018;8(9):1674-1688. Link
  2. Chen X, Ling X, Zhao L, Xiong F, Hollett G, Kang Y, Barrett A, Wu J. “Biomimetic Shells Endow Sub-50 nm Nanoparticles with Ultrahigh Paclitaxel Payloads for Specific and Robust Chemotherapy.”  ACS Appl Mater Interfaces. 2018 Sep 25. doi: 10.1021/acsami.8b11571. PMID: 30203956  Link
  3. Hedgire S, Krebill C, Wojtkiewicz GR, Oliveira I, Ghoshhajra BB, Hoffmann U, Harisinghani MG. “Ultrasmall superparamagnetic iron oxide nanoparticle uptake as noninvasive marker of aortic wall inflammation on MRI: proof of concept study.”   Br J Radiol. 2018 Sep 12:20180461. doi: 10.1259/bjr.20180461. PMID: 30160173  Link
  4. Application of the BLADE Sequence in Upper Abdominal MR Imaging. Krebill C.  Radiol Technol. 2018 May;89(5):495-497. PMID:29793909 Link
  5. Torrado-Carvajal A, Vera-Olmos J, Izquierdo-Garcia D1, Catalano OA, Morales MA, Margolin J, Soricelli A, Salvatore M, Malpica N, Catana C1. Dixon-VIBE Deep Learning (DIVIDE) Pseudo-CT Synthesis for Pelvis PET/MR Attenuation Correction. J Nucl Med. 2018 Aug 30. pii: jnumed.118.209288. doi: 10.2967/jnumed.118.209288. PMID: 30166357  Link
  6. Xiaoyuan Ji, Jie Wang, Lin Mei, Wei Tao, Austin Barrett, Zhiguo Su, Shaomin Wang. Guanghui Ma, Jinjun Shi, Songping Zhang. Artificial Photosynthesis: Porphyrin/SiO2 /Cp*Rh(bpy)Cl Hybrid Nanoparticles Mimicking Chloroplast with Enhanced Electronic Energy Transfer for Biocatalyzed Artificial Photosynthesis. Advanced Functional Materials. Link
  7. Yang KS, Im H, Hong S, Pergolini I, Del Castillo AF, Wang R, Clardy S, Huang CH, Craig Pille, Ferrone, Yang R, Castro CM, Lee H, Del Castillo CF, Weissleder R. Multiparametric plasma EV profiling facilitates diagnosis of pancreatic malignancy. Sci Transl Med. 2017; 9(391): eaal3226. PMC5846089
  8. Zhu X, Ji X, Kong N, Chen Y, Mahmoudi M, Xu X, Ding L, Tao W, Cai T, Li Y, Gan T, Austin Barrett, Bharwani Z, Chen H, Farokhzad OC. Intracellular Mechanistic Understanding of 2D MoS2 Nanosheets for Anti-Exocytosis-Enhanced Synergistic Cancer Therapy.  ACS Nano. 2018 Mar 27;12(3):2922-2938. PMC6097229
  9. Miller MA1, Kim E, Cuccarese MF, Alec Plotkin, Prytyskach M, Kohler RH, Pittet MJ, Weissleder R. “Near infrared imaging of Mer tyrosine kinase (MERTK) using MERi-SiR reveals tumor associated macrophage uptake in metastatic disease.” Chem Commun. 2017 Dec 19;54(1):42-45. PMC5736449
  10. Ding L, Zhu X, Wang Y, Shi B, Ling X, Chen H, Nan W, Austin Barrett, Guo Z, Tao W, Wu J, Shi X. “Intracellular Fate of Nanoparticles with Polydopamine Surface Engineering and a Novel Strategy for Exocytosis-Inhibiting, Lysosome Impairment-Based Cancer Therapy”. Nano Lett. 2017 Nov 8;17(11):6790-6801.  PMC6071871
  11. Yoo B, Ann-Marie, Billig, Medarova Z. “Guidelines for Rational Cancer Therapeutics. Frontiers in Oncology Journal”. Front Oncol. 2017 Dec 12;7:310. PMC5732930
  12. Gharagouzloo C, Timms L, Qiao J, Fang Z, Joseph Nneji, Pandya A, Kulkarni P, van de Ven AL, Ferris C, Sridhar S. “Neural circuits and brain function: New insights using quantitative vascular mapping of the rat.” Neuroimage, 2017. 16C:24-33  PMC5824692
  13. Gharagouzloo C, Timms L, Qiao J, Fang Z, Joseph Nneji, Pandya A, Kulkarni P, van de Ven AL, Ferris C, Sridhar S.   “Dataset on a 173 region awake resting state quantitative cerebral blood volume rat brain atlas and regional changes to cerebral blood volume under isoflurane anesthetization and CO2 challenge”. Data in Brief, 2018. 17:393-396.  Link
  14. Qin L, Li A, Qu J, Reinshagen K, Li X, Cheng S, Annie Bryant, Young GS. Normalization of ADC does not improve correlation with overall survival in patients with high-grade glioma (HGG). J Neurooncol. 2018 Apr;137(2):313-319.   PMC6071871
  15. Belz J, Kumar R, Baldwin P, Noelle Castilla Ojo, Leal AS, Royce DB, Di Zhang D, van de Ven AL, Liby K, Sridhar S. “Sustained-release Talazoparib implants for localized treatment of BRCA1-deficient breast cancer”. Theranostics, 7(17): 4340-4349.  PMC5695017
  16. Qin L, Li X, Amanda Stroiney, Qu J, Helgager J, Reardon DA, Young GS. “Advanced MRI assessment to predict benefit of anti-programmed cell death 1 protein immunotherapy response in patients with recurrent glioblastoma.” 2017 Feb;59(2):135-145.  PMC6097616
  17. Jodi Belz, Noelle Castilla Ojo,Srinivas Sridhar, Rajiv Kumar.  Radiosensitizing silica nanoparticles encapsulating docetaxel for treatment of prostate cancer, In Cancer Nanotechnology. Reema Zeineldin (Ed).  Series: Methods in Molecular Biology. Springer Press. Methods Mol Biol. 2017; 1530:403-409. PMC5531609
  18. Christian Berrios, Megha Padi, Mark A. Keibler, Donglim Esther Park, Vadim Molla, Gregory Stephanopoulos, John Quackenbush, James A. DeCaprio. “Merkel cell polyomavirus small T antigen promotes pro-glycolytic metabolic perturbations required for transformation”. 2016 Nov 23;12(11):e1006020.   PMC5120958
  19. Song C, Liu Y, Rachel Fontana, Makrigiorgos A, Mamon H, Kulke MH, G. Mike Makrigiorgos. “Elimination of unaltered DNA in mixed clinical samples via nuclease-assisted minor-allele enrichment”.  2016 Nov 2;44(19):e146. PMC5100565
  20. Andrew L. Hong, Yuen-Yi Tseng, Glenn S. Cowley, Oliver Jonas, Jaime H. Cheah, Bryan D. Kynnap, Mihir B. Doshi, Coyin Oh, Stephanie C. Meyer, Alanna J. Church, Shubhroz Gill, Craig M. Bielski, Paula Keskula, Alma Imamovic, Sara Howell, Gregory V. Kryukov, Paul A. Clemons, Aviad Tsherniak, Francisca Vazquez, Brian D. Crompton, Alykhan F. Shamji, Carlos Rodriguez-Galindo, Katherine A. Janeway, Charles W. M. Roberts, Kimberly Stegmaier, Paul van Hummelen,
Michael J. Cima, Robert S. Langer, Levi A. Garraway, Stuart L. Schreiber, David E. Root,
William C. Hahn, & Jesse S. Boehm. “Integrated genetic and pharmacologic interrogation of rare cancers”. Nat Commun. 2016 Jun 22;7:11987.  PMC4917959
  21. Wang P, Yoo B, Sherman S, Mukherjee P, Ross A, Pantazopoulos P, Petkova V, Farrar C, Medarova Z, Moore A. “Predictive imaging of chemotherapeutic response in a transgenic mouse model of pancreatic cancer.” Int J Cancer. 2016 Aug 1;139(3):712-8. PMCID: PMC4925171
  22. Nazila Kamaly, Gabrielle Fredman, Jhalique J. Fojas, Manikandan Subramanian, Won II Choi, Katherine Zepeda, Cristian Vilos, Mikyung Yu, Suresh Gadde, Jun Wu, Jaclyn Milton, Renata Leitao, Livia Rosa, Moaraj Hasan, Huayi Gao, Vance Nguyen, Jordan Harris, Ira Tabas, and Omid C. Farokhzad. “Interleukin-10 Targeted Nanotherapeutics Developed with a Microfluidic Chip Enhance Resolution of Inflammation in Advanced Atherosclerosis”. ACS Nano. 2016 May 24;10(5):5280-92. PMC5199136