Research Highlight
MicroRNAs (miRNAs) are a class of non-coding RNAs that were recently discovered and are becoming increasingly studied for their role cells. MiRNAs are used by the cell in conjunction with the RISC complex to post-transcriptionally control the expression of proteins. It has been demonstrated that miRNAs are differentially expressed in different tissues throughout the body and correlated with the pathology of cancer and other diseases. Using the differential expression of miRNA, diagnostic and therapeutic processes can be developed. A previous study analyzed the miRNA expression in BALB/c mice implanted with a 4T1 cell line. Candidate miRNAs were identified based on differential expression in metastatic sites versus the primary tumor. A miRNA was selected, based on the predicted mRNA targets, to be studied in vitro. Mimics of the miRNA will be used to study the effects of restoring expression of the miRNA in 4T1 and MDA-MB-231 cell lines. Understanding the miRNA’s mechanism will allow for the design of a diagnostic or therapeutic device to better treat metastatic cancers. Project 2: Carboxylmethyldextran-coated superparamagnetic iron oxide nanoparticles (SPIONs) can be viewed using magnetic particle imaging, which is an imaging method allowing for high resolution with high contrast. I am developing a protocol to attach fibrin-adherent peptides to the SPIONs. Fibrin is the principle protein constituent of clotted blood. The SPIONs are quickly pulled from circulation, leaving the SPIONs adhered to the blood clot. This method will be studied for future clinical use in identifying and imaging thromboses.
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:
In vivo imaging of targeted drug delivery to HER2 positive cancer cells
Nanomedicine for Safe Healing of Bone Trauma
The Assessment and Comparison of Ferumoxtran as Contrast Imaging Agent in Patients with Pancreatic Cancers.
The Nano-plasmonic Exosome (nPLEX) Assay for Pancreatic Ductal Adenocarcinoma Diagnosis and Prognosis
Iron-chelating PEG-like nanoprobes as therapeutic and 89Zr/PET imaging agents
Integrated diffraction-based diagnostic for point-of-care screening
Use of CT Texture Analysis for Characterization and Prognostication of Incidental Adnexal Lesions
Characterization of Targeted PARP-inhibitor Nanoformulations In Vitro and In Vivo
Investigating the use of iron chelator deferoxamine (DFO)-bearing PEG-like nanoprobes as a multifunctional agent for cancer therapy and PET imaging
PDT and PIT with Chemotherapy for Treatment of 3D Ovarian Cancer Nodules Under Flow and Static Conditions
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
Combined delivery of targeted liposomal chemotherapeutics and photodynamic therapy to treat pancreatic cancer
Development of a Point of Care Assay for Detecting High Risk HPV in Resource Limited Settings
Erythropoietin improves antitumor immune response through reversal of the hypoxic tumor microenvironment
Implementation of novel MR-based attenuation correction in PET/MR pelvic scans
Multiplexed cellular fluorescent imaging in head and neck squamous cell carcinomas (HNSCC) for different markers to predict patient specific response rates to immunotherapy and for mapping of the tumor microenvironment (TME).
Analyzing metastasis through targeted miRNA nanotherapy in aggressive breast cancer
Assessing the reproducibility of MRI-based brain tumor measurements between both observers and MRI vendors
Capture of circulating tumor DNA through the use of biotinylated poly-lysine affixed to gold nanoparticles
Optimizing murine cells for in vitro modeling of high-grade serous ovarian cancer
Using smart biomaterials with immunoadjuvants to treat metastatic breast cancer
Longitudinal assessment of tumor heterogeneity during immunotherapy for metastatic melanoma
Evaluation of deep learning approaches in an integrated PET/MRI scanner to generate pelvis attenuation maps and characterize prostate cancer
The Role of CD8+ and CD4+ in the Tumor Microenvironment (TME) after Controlled Exercise in E0771/M3C Breast Cancer Models
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.
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.
- Patrick Sheedy, Zdravka Medarova. The fundamental role of miR-10b in metastatic cancer. Am J Cancer Res 2018;8(9):1674-1688. Link
- 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
- 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
- Application of the BLADE Sequence in Upper Abdominal MR Imaging. Krebill C. Radiol Technol. 2018 May;89(5):495-497. PMID:29793909 Link
- 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
- 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
- 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
- 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
- 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
- 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
- Yoo B, Ann-Marie, Billig, Medarova Z. “Guidelines for Rational Cancer Therapeutics. Frontiers in Oncology Journal”. Front Oncol. 2017 Dec 12;7:310. PMC5732930
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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