The Cores
The NanoTumor Center consists of six cores and six projects. Description, function and goals of each core are described below.
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Administrative Core
Leaders: Sadik Esener and Ira Goodman
The Administrative Core provides central programmatic leadership, governance, coordination and associated support services to the NanoTumor Center.
The primary function of the Administration is to manage future planning, and to facilitate communication between investigators, projects, cores, and other consortium participants. In so doing, the Administrative Core develops and implements policies and procedures and guides daily operations.
This Core manages the allocation and distribution of CCNE resources (personnel, funds, equipment, and supplies) and coordinates the functions of the advisory and monitoring groups overseeing the NanoTumor Center's performance.
The Administrative Core personnel include the NanoTumor Center director, deputy directors, senior administrator, program assistant and information technology specialists. Through these key personnel, the Core manages the NanoTumor Center's scientific, administrative and financial activities.
A major effort of the Administrative Core is building an informatics network to link the investigators, projects and sites together and to create repositories for shared data.
Scientific leadership is supported by multiple committees including the internal Steering Committee and the Scientific Assessment Committee and external Coordinating and Governance Committee.
The director makes the final decisions, utilizing advisory and management committee recommendations.
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Pharmacology/Toxicology Core
Leader: Stephen Howell
The work proposed in this Core is an integral part of a large research project in cancer pharmacology directed at the development of new therapeutic principles using nanotechnology.
Nanoscale particles and devices are similar in size to biomolecules and can easily enter most cells. Our ability to manipulate the physical, chemical, and biological properties of these particles affords researchers the ability to engineer and use nanoparticles for drug delivery, as image contrast agents, and for diagnostic purposes.
Scientists in the NanoTumor Center will be generating nanoscale particles and devices, made out of novel materials that are intended for use in humans. The NanoTumor Center will perform preclinical toxicology, pharmacology, and efficacy testing of nanoscale devices using animal models and cultured human cell lines. Pharmacologic and toxicologic assessment of these particles in animal models is an essential step in their preclinical development.
The mission of Pharmacology and Toxicology Resource (PTR) will be to provide GLP pharmacokinetic (PK), pharmacodynamic (PD) and toxicologic (TOX) services to NanoTumor Center investigators utilizing the assay cascade and protocols developed by the Nanotechnology Characterization Laboratory for Cancer Research in conjunction with the FDA.
In vivo studies will be carried out in mice and rats; in vitro studies will utilize human cell lines.
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Imaging/Modeling Core
Leaders: Robert Mattrey and Michael Bouvet
This Core brings together three established teams for mouse imaging and orthotopic and genetically induced tumor models. It will not only provide the animal models but also in vivo non-destructive imaging to detect tumors or devices. Providing animal models is essential for this NanoTumor Center grant as it includes investigators from the physical sciences with limited animal experience.
The Core will be able to perform entire experiments for investigators. The Genetically Induced Murine Tumor Service is staffed with trained personnel that provide all the needed services to study and/or image native breast tumors and leukemia in genetically susceptible mice.
The Dept of Radiology and the Cancer Center at UCSD has established a Small Animal Imaging Resource (SAIR) to support cancer research. The dedicated rodent imaging facility (~650 ft2) located adjacent to the vivarium houses optical, CT, PET and ultrasound imaging, as well as a high-resolution digital autoradiography and fluorescent imaging system for post-mortem analysis. The SAIR also provides rodent MRI on a 7T system located about one mile from the Cancer Center adjacent to another vivarium. Support and expertise include: imaging, animal care, image computation, MR & optical hardware and software, diagnostic agent chemistry, radiochemistry including cyclotron, analytical chemistry, kinetic modeling and parametric imaging, anatomic and histological confirmation.
The imaging team is developing molecular imaging approaches to provide non-invasive biomarker detection, characterization and monitoring of tumors. There are three high priority goals for the imaging team: 1) Optimize image acquisition and blood sampling to enable kinetic modeling to better evaluate agent distribution; 2) Co-register imaging data to post-mortem slices to provide accurate anatomic confirmation and accurate image-guided tissue sampling of regions of interest for further analysis; and 3) Complete automation of imaging data reduction for kinetic modeling including co-registration of the multiple volume acquisitions to accurately define the time-intensity-curve on a volumetric basis and the generation of parametric images to improve throughput and eliminate operator bias.
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Biocomputing Core
Leader: Shankar Subramaniam
The Computational Core has been designed with two major aims in mind: (1) providing a data capture, fusion, and sharing environment with large-scale automation and an integrated software stack, and (2) discovering incipient cancer, and pre- and post-treatment temporal monitoring of its evolution by analyzing captured time series of biological processes using multivariate state estimation techniques and other kernel-based technologies for the first time.
The realization of global data sharing, analysis, and coherence requires software (not hardware) architecture that is essentially an integrated stack interfacing any data capture device with routers, computers, network management software, and databases, all of which are connected to the internet but not yet able to communicate. This Core will show how the architecture is realized and use it with project data to find incipient disease using sophisticated algorithms and a great deal of medical intuition from the team. In time, nanosensor technologies will be created and integrated into the data capture and intervention cycle, yielding even greater temporal resolution and therefore, higher probability of accurate and specific disease identification and treatment.
There are two high impact benefits of successful work: (1) ubiquitous access to global data through the internet physical layer in the coming years, and (2) a new method for collecting and analyzing data to find incipient disease.
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Synthesis/Fabrication Core
Leaders: Evelyn Hu and William Trogler
The Synthesis/Fabrication Core will provide custom chemistry and nanofabrication essential to the success of several research areas. For example, coupling the specificity of monoclonal antibodies to nanodimension features on a sensor chip requires the development of chemical linkers with the requisite specificity. This requires combining the demands of the surface materials chemistry with protein chemistry to prepare linking agents of high purity and selectivity. Expertise in this Core area is essential to a wide range of biomedical applications that require binding of enzymes, antibodies, or cells to micro or nanofabricated materials.
In addition, the Synthesis Core will provide expertise in the construction of cationic core shell dendrimers in the 40 - 200 nm range and hollow silica and titania shells in the sub 100 nm range. These nanoparticles will ultimately incorporate drug-DNA delivery, imaging, and cell-specific recognition capabilities, which are relevant to a broad range of therapeutic and diagnostic medical applications.
Fabrication of nanotechnology devices will be performed at the nanofabrication facility, which includes an 11,000 ft2 clean room. It will provide the critical infrastructure for the fabrication of microfluidic structures, and well controlled, critically shaped, selectively modified micro- and nanostructures. The primary tools will be a complete set of lithographic techniques for compound semiconductor device fabrication, including contact aligners, and an i-line stepper for optical lithography, a JEOL JBX-5DII Electron Beam writer (soon to be augmented by a newer version JEOL e-beam writer). A full range of deposition and etching tools is included, with the capability to etch very deep channels (~100 microns) into silicon and compound semiconductor substrates. For cost-effective production, large areas of different chemically functionalized regions could be fabricated on chips through the use of 'chemical stamps' formed from silicon or silicon dioxide. A Nanonex 2000 Nanoimprinter in the facility will allow rapid imprinting of chemical or mechanical patterns onto surfaces as large as 8 inches in diameter.
The Fabrication Core will provide a broad range of micro and nanofabrication services, including microfludic interfaces that are essential for the fabrication of practical devices. Characterization and assessment of nanoscale devices will also be carried on within the Core or through shared facilities (i.e., SEM, TEM, AFM, SIMS).
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Education Core
Leaders: Sarah Blair and Tina Huth
The overall objective of the Educational Core is to facilitate community outreach and education for applications of nanotechnology and oncology. Community outreach and education will be achieved through: 1) Education in nanotechnology and cancer for students, faculty and staff of participating institutions; 2) Enhanced communication among students, faculty and staff within and between member institutions through group educational opportunities and net based portals; 3) Education and awareness in nanotechnology applications in cancer for community health care providers in oncology.
To achieve the objectives identified above, the following specific aims are included: 1) Identification, collection, organization and communication of courses at member institutions in nanotechnology and oncology; 2) Creation of seminar series to focus on nanotechnology and oncology; 3) Development, implementation, webcast and archive of forums and workshops to facilitate discussions and exchange of ideas; 4) Outreach to community health care providers in oncology through on-site seminars, webcasts, and internet portal; 5) Institute workshops at national meetings with presentations by all the CCNE's.