Jennifer L. West - US grants

The goal of this proposal is the development of polymeric scaffolds for cardiovascular tissue engineering which will lead to the production of tissue-based small diameter vascular grafts. Hydrogel polymer scaffolds will be formed by rapid photopolymerization of aqueous precursors which allows for the incorporation of cell suspensions within the final product. Cell viability is maintained during this process, and the focus will be on the use of genetically engineered smooth muscle and endothelial cells. The incorporation of a variety of bioactive domains within the structure of the hydrogel matrices will be investigated to promote cell adhesion, growth, and extracellular matrix synthesis. Bioactive domains to be incorporated will include cell adhesion peptides and peptide growth factors. Cells will be transduced with genes that encode NO synthase for NO production (a proven anti-thrombotic agent), an endothelial cell-specific growth factor (VEGF), lysyl oxidase to enhance matrix crosslinking, and protease inhibitors (TIMPs) to reduce matrix degradation. In vitro assessment of cell viability and proliferation, extracellular matrix synthesis, and transgene expression will be performed under conditions of flow and static culture. Polymer preparations and polymer/cell composites will be tested using small animal in vivo vascular injury models for the recruitment of endothelial cells and the maintenance of homeostasis. Coating of Dacron grafts with polymers and polymer/cell composites will be investigated both in vitro and in vivo in canine arteriograft modalities. The ultimate focus of this proposal is to develop polymers which are biodegradable and can be used to support cell growth and deposition of extensive extracellular matrix material for de novo synthesis of vascular tissue. Populations of vascular cells (smooth muscle and endothelial cells) will be introduced as suspensions to the polymer environment prior to crosslinking of the hydrogel. Genetic engineering of cells will be used to optimize their production of matrix materials for the formation of tissue structures with mechanical integrity and to introduce anti- thrombotic properties to the newly formed tissue. The proposal seeks to develop vascular tissue grafts based on the provision of a biodegradable structure which will serve as a temporary scaffold and which will promote the proliferation and extracellular matrix elaboration of normal and genetically enhanced cell populations.

9821049
Halas
A new approach to biosensing utilizing nanoparticles with specifically engineered electromagnetic resonances is proposed. Two specific goals are targeted: (I) the fabrication and demonstration of an all optical in vivo glucose sensor, and (2) The development of a streamlined, all optical bioassay for the detection of plasma proteins in whole blood. Metal Nanoshells, composite nanoparticles consisting of a dielectric core and an ultrathin gold shell, possess a strong plasmon excitation whose resonant frequency is controlled by the particle core diameter and shell thickness. By varying the nanoparticle's core/shell ratio, this resonance may be positioned at any wavelength across much of the visible and near infrared regions of the spectrum. When the nanoshell plasmon is resonant with a Raman excitation laser, enormous surface enhanced Raman scattering (SERS) enhancements have been observed from molecules adsorbed to the individual nanoshells. These enhancements occur without contributions from nanoparticle aggregation, as is typical with solid metal nanoparticle SERS enhancements. This effect provides a highly sensitive, high information content all-optical probe of molecular species in the local vicinity of individual nanoparticles suspended in a solution or other media. In addition, the plasmon resonance may be placed in a spectral "water window" of high infrared transmissivity in biological fluids and tissue, facilitating simple in vitro and in vivo sensing designs. Protein-conjugated nanoshell species, synthesized using the many well-established protocols of immunogold, will be utilized as specific functional agents in the development of new optically-based biosensing applications. Both sensor projects consist of bioconjugate-nanoshell attachment and activity studies, a series of nanoshell SERS-enhanced Raman spectroscopic studies for the biochemical species and reactions of interest, and characterization of the Raman-based monitors versus standard calibration methods. In the case of the glucose sensor development these investigations will be followed by incorporation of the bioconjugate-nanoshell species into hydrogel media and in viva in the final stage. This project provides an exciting, goal oriented interdisciplinary series of studies that combines expertise in nanoparticle synthesis, immunochemistry, Raman and infrared spectroscopy, and quantitative and statistical analysis. The work described in this proposal is consistent with the demonstrated expertise of the two Principal Investigators. This project will stimulate and unite graduate students in the disciplines of electrical engineering, applied physics, bioengineering and biochemistry toward goals of major technical and societal impact.
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9875607
West
Restenosis is a prevalent and life threatening complication of angioplasty and other vascular procedures used to re-open occluded arteries. Approximately 45% of all angioplasty procedures fail due to restenosis. Restenosis is due in large part to the proliferation and migration of smooth muscle cells to form of an occlusive layer of tissue, similar to scar tissue, within the arterial wall. Though the mechanisms of restenosis are as yet poorly understood, it is clear that initial thrombosis following vascular injury plays an important role and that numerous growth factors and cytokines are involved in stimulation of smooth muscle cell proliferation, migration, and matrix production. Nitric oxide (NO), produced by endothelial cells in uninjured arteries, acts to limit smooth muscle cell proliferation, prevent platelet aggregation, increase the rate of endothelial cell proliferation and migration, and attenuate leukocyte adhesion. All of these actions are expected to decrease the incidence and extent of restenosis after vascular injury, such as that caused by angioplasty.

The proposed research involves the development of biofunctional polymeric biomaterials that produce NO under physiological conditions and that can be crosslinked via photopolymerization to form hydrogels in situ, allowing one to coat the surface of the damaged artery or a cardiovascular device with a thin layer of NO-producing hydrogel. The proposed materials have potential as a therapy for thrombosis and restenosis and as a novel tool to study the cellular and molecular actions of NO without systemic effects. Two classes of NO-releasing polymers will be synthesized, one based on S-nitrosothiols (which produce NO for hours to days) and another based on NO/nucleophile complexes (which produce NO for weeks to months), with polyethylene glycol (PEG) composing the bulk of the material for biocompatability and acrylate termini to allow rapid photopolymerization into hydrogel materials. The efficacy of these novel materials for the prevention of smooth muscle cell proliferation and the stimulation of endothelial cell proliferation will be assessed using cultured cells. Platelet aggregation will be assessed, and prevention of thrombosis will be evaluated in an ex vivo parallel plate blood flow assembly.

This research project will provide hands-on training for graduate, undergraduate, and high school students. This proposal addresses several additional educational goals. Dr. West will develop a novel biomaterials module for the undergraduate bioengineering laboratory course: this course will be designed to maximize the integration of teaching with research and thus encourage undergraduate students, as well as more faculty members, to participate in the undergraduate research program. All of the researchers involved in the project described above will actively participate in community outreach programs, including visiting local public high schools to present their research and educate the community about advances in bioengineering.

This IGERT award supports the establishment of an interdisciplinary research training program in the emerging field of cellular engineering. The program focuses on metabolic and tissue engineering and provides science and engineering students with rigorous educational and research training in the fields of bioengineering, biochemistry, and cell biology. A co-supervision system is created in which students will have an advisor from the Department of Bioengineering and an advisor from the Department of Biochemistry and Cell Biology for guidance of mechanistic and design aspects of research projects. The fundamental curriculum for IGERT trainees includes coverage of scientific ethics, advanced laboratory skills, basic biosciences (biochemistry and cell biology) and engineering systems analysis. Student participants work in cooperative environments including team design projects and an industrial internship program with companies engaged in cellular engineering. This program is coordinated with a pre- and post internship seminar program to maximize the impact of the students' industrial experiences. The establishment of a visiting scientist position and a focused seminar series having different annual themes provides in depth exposure to new areas. A key component of the program will be continued expansion of our successful undergraduate recruitment program for underrepresented minorities to this specialized area of graduate education. Building upon established strengths in interdisciplinary research and education, this training program creates a center of excellence in cellular engineering that will train researchers who can utilize advances in biological sciences to produce innovative and cost- effective biotechnological products in the 21st century.

IGERT is an NSF-wide program intended to meet the challenges of educating Ph.D. scientists and engineers with the multidisciplinary backgrounds and the technical, professional, and personal skills needed for the career demands of the future. The program is intended to catalyze a cultural change in graduate education by establishing new, innovative models for graduate education and training in a fertile environment for collaborative research that transcends traditional disciplinary boundaries. In the fourth year of the program, awards are being made to twenty-two institutions for programs that collectively span all areas of science and engineering supported by NSF. The intellectual foci of this specific award reside in the Directorates for Engineering; Biological Sciences; and Education and Human Resources.

0221544
Drezek
The proposed project leverages recent advances in nanoparticle technologies to develop innovative contrast agents which can be optically interrogated using noninvasive approaches and targeted to specific molecular signatures of disease. The contrast agents proposed - nanoshells and nanoemitters - possess ideal optical and chemical properties for optical imaging. The optical response of these particles can be precisely and systematically varied over a broad band including the visible and infrared spectral regions. The extremely agile. tunabilityof the optical resonance is completely unique to nanoshells: in no other molecular or nanoparticle structure can the resonance of the optical extinction properties be systematically. designed. Moreover, the nanoparticles are highly biocompatible and proteins (such as antibodies) are readily conjugated to their surfaces. To develop the potential of nanoparticles as contrast agents for optical imaging, the investigators will study a novel class of exogenous contrast agents designed and optimized to address the clinically important problem of detection of pre.invasive neoplasias.

DESCRIPTION (provided by applicant): The goal of this research is to elucidate the influences that control smooth muscle cell (SMC) differentiation and prevent SMC de-differentiation in culture in order to optimize construction and performance of tissue engineered vascular grafts. Initially, we will study the behavior of mature SMCs in our culture systems. However, because of the potential difficulty associated with obtaining and maintaining differentiated SMCs from adult patients, we will also investigate the potential of two types of SMC progenitors (embryonically-derived 10"1"1/2cells and adult marrow-derived mesenchymal cells), which represent potential cell sources for allogeneic or autologous graft creation, to generate functional, differentiated SMCs in our system. We hypothesize that through control of both biochemical and biomechanical stimuli, attempting to recapitulate the environments experienced during embryonic vascular development, induction and/or maintenance of SMC differentiation can be maximized and that this will lead to improved structural integrity and performance of tissue engineered vascular grafts. The goal of each of the specific aims is to attempt to recapitulate certain developmental conditions and to determine the effects of these biochemical and biomechanical stimuli on differentiation of SMC progenitors and/or maintenance of SMC phenotype for vascular tissue engineering. In each of the aims, studies will first be conducted in 2D culture to characterize cellular responses to TGF-b on surfaces that provide defined ligands for cell adhesion. Following this, cells will be cultured in 3D bioactive hydrogel scaffolds designed to present the optimal combination and quantity of biological factors, as determined in the 2D studies, and to confirm the translation of results from 2D to 3D. Finally, cells will be cultured in 3D tubular constructs formed from bioactive, hydrogel scaffolds in a pulsatile flow bioreactor to evaluate the role of mechanical conditioning in SMC differentiation as well as the possible synergistic effects of biochemical and biomechanical stimulation. Adult and embryonic flow conditions will be evaluated. This course of studies will be performed for each cell type.

This grant supports the acquisition of a scanning electron spectroscopy for chemical analysis (ESCA) instrument for interface characterization of bio- , geo- and nanomaterials at Rice University. ESCA, also known as x-ray photoemission spectroscopy (XPS), is a powerful and versatile method for evaluating the surfaces of complex materials. The characterization of material interfaces is an important activity in much of materials research; for bio-, geo- and nanomaterials it is essential for developing new materials and understanding their properties. It is intrinsically a surface technique sensitive only to the top several angstroms of a sample, but with the appropriate conditions can be used to probe depths up to 20 nanometers. Several projects require depth profiling of atomic concentrations at surfaces while others need information about the nature of chemical bonding at interfaces. Still others are interested in chemical mapping of interfaces at the tens of micron level. Nearly all participants must be able to measure the atomic composition of surfaces, and the ability to analyze multiple samples quickly and consistently is of particular value. ESCA can measure the relative amounts of carbon and nitrogen at a surface and can determine whether the carbon is graphitic or bound to nitrogen. ESCA works by bombarding surfaces with a controlled X-ray source and resolving the kinetic energy of the photoemitted electrons; these energies are then used to identify surface atoms and their chemical state. Both the relative amounts of atomic species at surfaces, as well as their chemical environment can be deduced from XPS data. Though samples are evaluated under vacuum conditions, the technique is flexible- conductive and non-conductive powders and thin films have been analyzed with this method. The specific system has a focused, intense x-ray source, leading to small spot sizes (10 microns and high x-ray flux. This feature speeds data collection and its large sample platforms allow for rapid analysis of multiple samples. The scanning capability also enables a wider range of surface chemical experiments, such as depth profiles of atomic composition near surfaces and chemical mapping at the tens of micron length scale.

The acquisition of a scanning ESCA will be especially significant to student training and development, specialized courses for undergraduates and graduates, and workshops. Over thirty graduate students, and tens of post-docs and undergraduates will be able to use this system to understand how surface chemistry plays a role in their research. The existence of a scanning ESCA will allow us to implement a set of programs that not only teaches students how to use the instrument, but also highlights the importance of interface chemistry in areas such as bio- and nanoengineering.

DESCRIPTION (provided by applicant): The Biotechnology Training Program at Rice University provides high quality interdisciplinary training to prepare pre-doctoral trainees for research careers in academic and industrial biotechnology. It is administered by the interdisciplinary Institute of Biosciences and Bioengineering (IBB), with faculty mentors from biochemistry &cell biology, bioengineering, chemistry, and chemical &biomolecular engineering. The presence of this training program in IBB has been catalytic for interactions among faculty and students and has provided key support for education and research training activities. It has been central to development of a new Department of Bioengineering, with a top-10 ranked graduate program. The requested number of pre-doctoral trainees for the program is 12. The trainees are selected after their first year of graduate studies for a two-year appointment based on academic performance, assessment of their potential as researchers, and their interests in biotechnology. Emphasis is given to recruiting and retaining students from under-represented ethnic groups through outreach activities, targeted recruiting, and mentoring programs. Trainees in this program take a core of interdisciplinary coursework in biotechnology, including 'Foundations of Biotechnology', a course sequence developed specifically for this program. Students also take a course in Responsible Conduct of Research. Trainees participate in a leadership workshop and an industrial internship as well. Special seminars are attended by trainees, including some seminars focused on research in the industrial setting meant to help prepare them for success on their internships. An annual research retreat provides the trainees with the opportunity to interact with each other, faculty, and with executives from local biotechnology companies. The physical facilities that support this program are outstanding, all either recently constructed or renovated, and in 2008 the program will move to a new building, a collaborative center for biotechnology, jointly occupied by Rice, Baylor College of Medicine, and M.D. Anderson.

[unreadable] DESCRIPTION (provided by applicant): For over fifty years, cancer has remained the second leading cause of death in the United States, accounting for over 25% of the deaths in the population. More than one million cases are diagnosed each year, resulting in over 500,000 deaths (American Cancer Society, 2001). Nanotechnology may offer new options for both diagnosis and treatment of cancer. A new nanoparticle-based approach to cancer therapy has been under investigation in our laboratory. Near infrared-absorbing nanoparticles are injected intravenously and allowed to accumulate in the tumor, due to the leaky vasculature and/or targeting, followed by illumination of the animal with near infrared (NIR) light. NIR light is not appreciably absorbed by tissue components, allowing deep penetration without damage to normal tissues. Using a class of NIR-absorbing nanoparticles called gold-silica nanoshells, we have demonstrated complete tumor ablation and long term survival of animals without tumor regrowth. We have recently begun in vitro studies with two other classes of NIR- absorbing nanoparticles - gold-gold sulfide nanoshells and gold nanorods. In vitro, we have been able to achieve much more rapid heating with these two newer types of nanoparticles due to their higher absorption and lower scattering (order of heating, nanorods, gold-gold sulfide nanoshells, gold-silica nanoshells), and thus believe that they have the potential to be more effective at lower doses in cancer therapy than gold- silica nanoshells. However, the sizes of these three classes of nanoparticles varies widely. Gold-silica nanoshells are approximately 100 nm in diameter, gold-gold sulfide nanoshells approximately 50 nm, and gold nanorods 20 nm. Thus, biodistribution of the particles will be quite different and may drastically affect therapeutic efficacy. We propose to evaluate biodistribution, biocompatibility and tumor ablation efficacy of these NIR-absorbing nanoparticles. The optimal particle formulation will be further examined in a model of medulloblastoma. [unreadable] [unreadable]

Cellular engineering is a field with enormous potential to make truly significant contributions to mankind in both medical and non-medical fields over the next decades. The next generation of therapeutics (following recombinant proteins and peptides) will likely utilize cells and tissues. Many new technologies in fields such as environmental engineering and chemical production will also be based on advances in cellular engineering. This exciting, interdisciplinary field, where Rice University offers great depth of research opportunities and expertise, will provide undergraduate students with exciting and impacting research experiences. Under this REU program, ten undergraduate will be selected each summer to work on any of a number of projects under the mentorship of faculty. Students will be recruited nationwide, with particular emphasis on recruiting women and under-represented minorities. The students will participate in cutting-edge research and professional development activities for 10 weeks each summer. More information is available at http://cohesion.rice.edu/CentersAndInst/IBB2/emplibrary/IBB2007SummerInternshipWebsite.pdf, or by contacting Dr. Jennifer West (Principal Investigator) or Kimberly M'Carver (Program Coordinator) at 713-348-6034 or Kimberly@rice.edu.

DESCRIPTION (provided by applicant): The overall goal of this initiative is to investigate the cellular uptake, trafficking, and sub-cellular localization of different classes and subtypes of nanoparticles (NPs) with well-defined physiochemical properties for the creation of a reference table that relates the sub-cellular distribution of NPs to their intrinsic physiochemical properties across a range of cell lines. The subcellular fate of NPs is relevant both in terms of the therapeutic efficacy and biosafety of the NPs. The effective impact of size, shape, charge, and chemical composition of nanomaterials, in the presence of serum opsonins, on both cellular entry and subsequent subcellular localization will be investigated. The expected outcome of this project is to create a reference table that accelerates the transition of nanomaterials from the bench to the clinic by rapidly expanding our knowledge of the effect of a material's intrinsic characteristics on its intracellular destination. The final product, a comprehensive table of NPs and their subcellular locations, will guide the future development of NP drug delivery systems for rapid expansion of biomedical applications, including cancer therapy, cardiovascular imaging, and gene therapy. PUBLIC HEALTH RELEVANCE: What this project seeks to deliver is a multi-dimensional reference table that relates the subcellular distribution and toxicity of NPs to their intrinsic physiochemical properties across a range of diverse cells and cell lines. It is our hope that the data generated from this project will serve as a resource for future research and encourage model development and new insights into nanotechnologies for imaging and drug delivery.

DESCRIPTION (provided by applicant): This training program provides a new type of experienced interdisciplinary scientist in the field of nanobiology, combining the tools, ideas and materials of nanoscience with biology to enable new approaches to research problems and develop novel diagnostic and therapeutic strategies. This new training program builds upon a very successful, interdisciplinary training initiative, supported for a limited duration of five years by the NIH Roadmap Initiative. Trainees from this program are uniquely prepared to explore the interplay between current nanoscience applications in high technology and biotechnology and biomedical applications for clinical and research medicine. Just as early molecular biology heralded a new era in both biological sciences and technology, nanobiology is poised to exploit the adventitious interface between nanoscience and biology. The Nanobiology Interdisciplinary Graduate Training Program (NIGTP) takes advantage of the strong history of multi-institutional, multi-disciplinary training efforts in the Keck Center of the Gulf Coast Consortia. This allows seamless organization of trans-institutional training programs. Bringing together six institutions - Baylor College of Medicine, Rice University, University of Houston, the University of Texas Health Science Center at Houston, University of Texas M. D. Anderson Cancer Center, and the University of Texas Medical Branch at Galveston - the NIGTP faculty bring significant expertise in nanobiology. Fifty faculty are included in this program, with over $63M awarded in research funding related to nanobiology and outstanding graduate research opportunities. Trainees will participate in a highly interdisciplinary curriculum to provide deep knowledge and also the connections between the disciplines. Trainees will also be required to have mentors in two different disciplines, with a mini-sabbatical period in the co-mentor's laboratory as an essential part of the multi-disciplinary training experience. Trainees will also participate in weekly seminars and journal club and will present their research at an annual retreat. RELEVANCE: The interface between nanotechnology, biology, and medicine is a new frontier for scientific exploration and for the creation of new and improved diagnostic and therapeutic tools to detect, treat, cure, and prevent human diseases. This grant would support an established interdisciplinary graduate training program in nanotechnology for biology and medicine.

An award has been made to Rice University that will provide cutting-edge research training and professional development activities for 10 weeks for 10 students, for the summers of 2010-2012. This award is supported by the Directorates for Biological Sciences (BIO) and Engineering (ENG). The specific focus of the NSF REU program is cellular engineering, a field with enormous potential to make truly significant contributions to mankind in both medical and non-medical fields over the next decades. The goal of the program is to expose students to cutting-edge technologies and approaches in metabolic and tissue engineering. The summer NSF REU features: research training in cellular engineering; weekly research seminars; training in ethics and the responsible conduct of research; leadership and mentorship retreats; safety training; special seminars and career development workshops; stipend and travel support; on-campus housing; participation in the "Advances in Tissue Engineering" short course; and a capstone research poster symposium. Students should expect an enriching and rigorous summer where they may nurture their professional and scientific development. Students will be recruited nationwide, with particular emphasis on recruiting women and under-represented minorities. Students will be selected based on the faculty steering committee's evaluation of each applicant's transcript, personal statement regarding interest and motivation for research, and letters of recommendation. Each year, a "Class Notes" newsletter of the NSF REU alumni will be published that features news on alumni's current academic or professional status and accomplishments. Assessment of this program is done via pre- and post-questionnaires as well by using the REU common assessment tool. More information on this NSF REU in cellular engineering is available at http://nsfreu.rice.edu, or by contacting Dr. Jennifer West (Principal Investigator) at 713-348-5955 or jwest@rice.edu.

DESCRIPTION (provided by applicant): Heart valve diseases require hospitalization of more than 90,000 Americans each year, but there are very few options for treating heart valve dysfunction, and even less is known about the mechanisms the underlie valve disease. The essential function of heart valves is made possible by the unique microstructural arrangement of fibrous extracellular matrix proteins within the valve leaflet tissue, but these valvular structure- function relationships have not been translated into the next generation of valve tissue engineering investigations and for in vitro analyses of valvular cell biology and disease. The primary microstructural attributes of aortic valves are their anisotropic nature and their interconnected, layered structure, which provide valvular interstitial cells (VICs) with heterogeneous pericellular environments. These characteristics are not provided by the polymer mesh scaffolds being investigated for tissue engineered heart valves (TEHVs), and there is little consensus about optimal strategies to produce a cellular leaflet scaffolds. Many groups including ours have investigated natural and synthetic gel-based scaffolds for studies of VIC biology and pathology, but these have generally seeded VICs within or atop homogeneous structures. Electrospinning can produce layered structures and anisotropy, but this approach is highly sensitive to operating parameters. We propose to integrate these heterogeneous structure and material characteristics of heart valves into hydrogel biomaterials. Hydrogel biomaterials (particularly poly ethylene glycol diacrylate, PEGDA) are appealing for use as TEHV scaffolds because they have tunable structure and mechanics, can be readily bio- functionalized, and can easily encapsulate cells. Research concerning these materials; however, has generally been focused on their biological activities, as opposed to the development of advanced material behavior. The goal of the proposed work is to apply novel patterning and layering methodologies to generate advanced 3D hydrogels that mimic the complex microstructure and material behavior of aortic valve tissues. We are ideally positioned to generate these materials, having expertise in the characterization of heart valve microstructure, material behavior, and mechanobiology as well as the use of patterning to govern biological ligand presentation and more recently to generate novel structures and regions of differential material behavior within PEGDA hydrogels. These advanced structures will have tremendous impact on the next generation of TEHV scaffolds and could also be used as more faithful biomimetic platforms for 3D investigations of valvular cell biology and disease mechanisms. The following aims will be performed to accomplish this goal: 1. Compare electrospinning, laser printing photolithography, and 2-photon absorption confocal patterning approaches to generate anisotropic hydrogels demonstrating a valve-like biological-shape stress-strain curve. 2. Optimize semi-interpenetrating approaches to develop composite laminate hydrogel scaffolds. 3. Pattern interconnecting structures into the layers of the composite laminate hydrogels.

The University of Texas Health Science Center at Houston (UTHSC-H), The University of Texas M.D. Anderson Cancer Center, Rice University and Albert Einstein College of Medicine have joined forces to form the Texas Center for Cancer Nanomedicine (TCCN). The TCCN brings together a multi-disciplinary, internationally recognized team of investigators to develop and translate nanotechnology-enabled innovation for improving the traditionally dismal outcome of ovarian and pancreatic cancers. The main research focus areas of the TCCN are: Multifunctional Nano-Therapeutics and Post-Therapy Monitoring Tools (Area 2 of the CCNE RFA), and Devices and Techniques for Cancer Prevention and Control (Area 3). By natural synergies of the underlying nano-platforms, the TCCN's investigations in focus areas 2 and 3 automatically provide a cadre of approaches for Area 1: Early Diagnosis Using In-Vitro Assays and Devices and In-Vivo Imaging Techniques. The TCCN has four projects and three cores. Projects 1 and 2 directly address ovarian cancer, and Projects 3 and 4 directly address pancreatic cancer. In each oncology focus area, one project involves multifunctional nanoplatforms for the delivery of bioactive agents to the tumors (Project 1- ovarian and Project 3- pancreatic), and the other, targeting approaches to the cancer-associated vascular endothelia (Project 2- ovarian and Project 4- pancreatic), for imaging and therapy. Both adenocarcinoma (Project 3) and endocrine pancreatic malignancies (Project 4) are considered in the TCCN. All Projects integrate fundamental investigations in cancer biology, nanotechnology platform development, and pharmaceutical sciences, albeit to different degrees. The cores are the Biomathematics Core, Targeting Core and Nanoengineering Core. All projects and Cores integrate with each other through the sharing of research results and nanotechnology platforms. This integration allows the TCCN to achieve clinical translation of its research breakthroughs, and aggressively manage the risks that are naturally associated with any highly innovative program at a rapid pace. To fuel translation to the clinic, several TCCN investigators have successfully developed spin-off companies based upon their research. Collectively, with a combination of synergistic projects supported by cores that provide services to each project and a track record of successful bench-to-bedside translation, the TCCN is uniquely positioned to bring forth highly effective nanotechnology platforms for prevention, therapy and monitoring of ovarian and pancreatic cancers.