Core 1: Animal Models Core

Core 2: Combinatorial Library Core

Core 3: Small Animal Imaging Core

Core 4: Pharmacokinetics, Biodistribution, and Biocompatibility Core

Shared research functions for the C-CCNE are organized into four “cores.”  These cores provide infrastructure and unique shared resources for CCNE projects, as well as facilitating interactions among projects.

Core 1: Animal Models Core.
Terry Van Dyke, Ph.D., Professor of Genetics, Core PI

This Core is led by Dr. Van Dyke who is nationally known for her work on genetically engineered mouse tumor models, particularly relating to the role of the Rb and p53 tumor suppressor pathways. Dr. Van Dyke shared the initial leadership of the NCI Mouse Models of Human Cancer Consortium and continues as an active PI on one of the MMHC grants featuring brain tumors.

This Core will support the animal model needs of Projects 1-5. A series of well-defined mouse tumor models are currently available at the LCCC, including genetically defined mouse models for breast, colon, pancreatic, melanoma, lung carcinoma, and brain tumors. Additional models for prostate and metastatic disease are available as CCNE projects mature. The Animal Models Core will maintain colonies of these animals and produce them for the investigators as needed. In cases where new transgenic and/or gene-targeted mouse lines may be required, the core will:

Associated technologies, such as cryopreservation and ovary transplants, are also available to support C-CCNE research.

Core 2: Combinatorial Library Research Core.

Rihe Liu, Ph.D., Assistant Professor of Medicinal Chemistry and Genome Sciences 
Bruce Sullenger, Ph.D., Professor of Surgery, Duke University
Brian Kay, Ph.D., Professor and Head, Biological Sciences, University of Illinois at Chicago

The focus of this Core is innovative research, and its output will be vitally important for Projects 1-6. Core 2 will use combinatorial library approaches to generate novel reagents having cell receptor selective binding abilities. Thus this Core will develop the ligands that confer ‘smartness’ (biological recognition) to smart nanoparticles (Projects 1, 2, 4), as well as assisting in generating novel biosensors that will be used in analysis of cellular signaling pathways (Projects 5,6).

This will be a ‘virtual core’ harnessing the capabilities of three dynamic investigators:

Dr. Bruce Sullenger, Professor and Vice-Chair for Research, Dept. of Surgery, Duke University. Dr. Sullenger is a leading investigator in the field of oligonucleotide aptamers.

Dr. Rihe Liu of the UNC School of Pharmacy. Dr. Liu has perfected a powerful technology based on very large libraries of peptide aptamers.

Dr. Brian Kay of the University of Illinois at Chicago, a leading expert on phage libraries.

These investigators are using their several combinatorial library screening approaches develop a series of peptide or oligonucleotide reagents that display high affinity and high selectivity for certain cell surface receptors being addressed in Projects 1,2 and 4 as well as to work with Dr. Hahn to develop sensors to be used in Projects 5 and 6. Thus this Core has undertaken important focused research that will result in the generation of novel ligands for cellular and molecular recognition that will play a vital role in essentially all of the projects.

Core 3: Small Animal Imaging Core. 
Weili Lin, Ph.D., Professor of Radiology
This Core will be directed by Dr. Weili Lin who has expertise in several aspects of imaging and who has published extensively in this area. The imaging core will provide SPECT, CT, OI, and MRI/MR imaging capabilities. A 9.4 Tesla MRI, has been funded and will be installed in renovated space in Year1 in the same building with optical imaging, micro CT and micro PET and animal holding space. Drs. Lin and Zhou are developing prototypes of carbon nanotube micro CT for this facility. These capabilities will provide key support to Projects 1,2 and 4 and will interface with the X-ray imaging approaches of Project 3.  Specific tasks of the Imaging Core will be to:

• determine the biodistribution of the nanoparticles developed in Projects 1, 2 and 4
• image tumors and follow tumor growth or regression in Projects 1, 2, 3, 4

Core 4: Pharmacokinetics, Biodistribution, and Biocompatibility Core (PK Core).
Frank Szoka, Ph.D., Professor, UCSF School of Pharmacy
Dr. Szoka is a pioneer in development of liposomes, nanoparticles and dendrimers as drug carriers. This includes basic research as well as applied research and development leading to technology commercialization. He also has vast experience in the pharmacokinetic/pharmacodyanmic analysis of carrier systems.

The Pharmacokinetics, Biodistribution, and Biocompatibility Core (PK Core) will be used for stringent testing of the in vivo behavior of nanoparticles. It will complement studies done at UNC-CH within Projects 2 and 4 and using the Small Animal Imaging Core. The task of the PK Core will not be routine evaluation of many types of nanoparticles, but rather detailed, unbiased, objective testing of leading nanoparticle candidates for further study. We visualize testing by the PK Core as a major stepping-stone to having our lead candidates evaluated by the NCI/NIST Nanotechnology Characterization Laboratory. In addition, this Core will provide novel pH-sensitive PEG compounds that will be used to ‘passivate’ the surfaces of nanoparticles in Projects 1,2 and 4. It will also provide a novel formulation of nanolipid particles that will be tested in Project 2. Finally this Core will allow testing of nanoparticle distribution via additional routes of administration (to the CNS and the lungs).