2010 — 2014 |
Wang, Yong |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Reversible Cell Capture and Release For Cell Separation @ Pennsylvania State Univ University Park
This NSF award by the Chemical and Biological Separations program supports work by Professor Yong Wang to apply nucleic acid aptamers to create a cell separation method. Cell separation has played an essential role not only in basic biological research, but in clinical diagnosis. Current methods for cell separation are mostly dependent on antibody-mediated cell recognition. However, antibodies or antibody-functionalized systems often exhibit limitations due to their easiness of losing functions and difficulty of reversing antibody-cell interactions. These shortcomings can significantly limit downstream cell analysis and applications. Thus, there is a clear need to discover and engineer alternative biomolecular ligands for cell separation applications. Because nucleic acid aptamers are different from antibodies and have numerous merits such as high affinity and specificity, great tolerance of harsh conditions, and easy synthesis with a standard chemical procedure, we hypothesize that nucleic acid aptamers can be used to develop a new method for cell separation. To test this hypothesis, we will systematically investigate biomolecular interactions between aptamers and cell receptors, understand intermolecular recognition in a multicomponent system, and explore the aptamer-mediated cell capture and release for cell separation.
The success of this research project will not only enable the development of a novel, universal cell separation method, but also enrich the current knowledge of biomolecular recognition and provide resourceful information for nucleic acid research. In addition to these technological impacts, this program will make impacts on human resource and education. First, this project will provide students with an interdisciplinary environment to learn biomolecular engineering, kinetic analysis, material development, and cell separation. The students will be able not only to acquire hands-on research skills, but also to learn analytical, communication, collaboration, and innovation skills. Second, the PI will initiate a new outreach program by collaborating with local high schools and continuously enroll K-12 students and teachers to the lab to learn cutting-edge techniques. Third, the students' research findings will be widely disseminated through publications in peer-refereed journals and presentations at national/international conferences.
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0.961 |
2010 — 2013 |
Wang, Yong |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Controlling Protein Release Via Intermolecular Hybridization @ Pennsylvania State Univ University Park
0967512 Wang
Protein drugs hold great promise for the treatment of various human diseases. However, efficient and safe delivery of protein drugs is a long-standing challenge in the field of drug delivery. Many protein delivery systems still suffer from problems including the rapid release of protein drugs, the inefficiency of controlling the release of multiple proteins, and the involvement of toxic molecules and/or harsh conditions during the preparation of protein delivery systems. This project is proposed to address these issues.
Intellectual merits: The objectives of the proposed research are to thoroughly understand the mechanisms of complementary oligonucleotide-mediated protein-aptamer dissociation, and based on this understanding, to develop a novel protein delivery method using nucleic acid aptamers, complementary oligonucleotides, and alginate hydrogels. Our novel hypotheses are: 1) aptamers can efficiently entrap one or multiple proteins in the alginate matrix because of their high binding affinity and specificity; 2) complementary oligonucleotides can be used as a molecular trigger to modulate protein release via hybridization with the aptamers; and 3) proteins can maintain a high level of bioactivity due to the mild procedure for hydrogel preparation and the protection by the aptamers. To test these hypotheses, preliminary studies have been carried out, showing that complementary oligonucleotides are capable of accelerating protein-aptamer dissociation. Encouraged by the compelling preliminary results, we will perform three tasks involving both experiments and mathematical modeling. The tasks are: 1) to investigate complementary oligonucleotide-mediated protein-aptamer dissociation, 2) to investigate the release of proteins from hydrogels in the presence or absence of complementary oligonucleotides, and 3) to develop a mathematical model to simulate the protein release process. We anticipate the outcomes of this study will be a deeper understanding of molecular recognition and a transformative method for protein delivery.
Broader impacts: The success of the proposed research will make several broad scientific and economical impacts. First, it will open a new avenue for the development of drug delivery systems. Second, it will enrich the knowledge of molecular recognition and provide valuable information for nucleic acid research. Third, the success of protein delivery will tremendously improve the treatments of various human diseases and save billions of dollars in healthcare costs. The broader impacts of this program will also be evident in our strong commitment to education and human resource development, which will have direct impacts on graduate, undergraduate, and K-12 students. First, this project will provide students with a unique intellectual environment to learn drug delivery, hydrogel synthesis, biomolecular engineering, kinetic analysis, cell characterization, and mathematical modeling. All participating students will have modularized scientific questions to study and will discuss their research findings in regular group meetings. The students will be able to not only acquire hands-on research skills, but also learn analytical, communication, collaboration, and innovation skills. In addition, the PI will incorporate the results acquired from the proposed research into the Drug Delivery course that is offered to both graduate and senior undergraduate students every spring semester. Second, we will initiate a new outreach program by collaborating with local high schools to teach the concepts of biomedical engineering in the Advanced Biology course. The results acquired by the participating students will be presented to high school students during the visits. In addition, we will continuously participate in the established outreach programs at UConn. These outreach efforts will raise high school students' interests in science and engineering and facilitate the development of a viable, sustainable science and engineering workforce. Third, the students' research findings will be widely disseminated through publications in peer-refereed journals and presentations at national/international conferences.
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0.961 |
2011 — 2015 |
Xu, Dianxiang (co-PI) [⬀] Tu, Michael (co-PI) [⬀] Wang, Yong Pauli, Joshua (co-PI) [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Mri: Acquisition of An Online Banking System For Information Assurance Research @ Dakota State University
Proposal #: 11-23220 PI(s): Xu, Dianxiang; Pauli, Joshua; Tu, Michael Institution: Dakota State University Title: MRI/Acq.: Online Banking System for Information Assurance Research Project Proposed: This project from an EPSCoR state, aiming to acquire hardware and software to create a banking testbed to explore issues of computer security of banking systems, enhances the future of security research for the global banking infrastructure. While online banking makes it more convenient to manage financial activities, security threats are becoming even greater because the money is stored on and moved around an untrustworthy Internet environment with increasing use of mobile, wireless devices. The proposed acquisition will enable various activities for promoting information assurance research and education in the banking sector. The proposed online banking system for South Dakota enables the following research projects in security: - Threat modeling and verification, aiming at a rigorous techniques with proof /disproof capability, - Security testing, aiming at cost-effective, automated security testing with threat models, - Forensic readiness, aiming at better investigation of intrusions and frauds, and - Security requirements analysis, aiming at consistent and testable specification. The work establishes a flexible research instrument for a key element of the nation?s financial infrastructure. The research enabled by the online banking system will lead to novel techniques for the defense, in-depth, of online banking applications. Broader Impacts: This instrumentation increases DSU?s capacity to conduct cutting-edge research on online banking security. The online banking system expands critical infrastructure in the new National Center for the Protection of the Financial Infrastructure. It also broadens the participation of students in research by providing a rich variety of research topics for the NSF REU (Research Experience for Undergraduate) Site in Information Assurance and Security, which places emphasis on recruitment of minority students. In terms of training the next generation workforce, far-reaching impacts are envisioned through improvements to the information assurance curriculum. The proposed system will be used to teach cyber security in computer classes at eight high schools through collaboration with the NSF project ?GK-12 Fellows in Cyber Security?. Two of these schools serve mainly Native-Americans. Finally, the instrument enhances PhD production in an EPSCoR state and solidifies DSU?s position in online banking research.
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0.973 |
2012 — 2017 |
Wang, Yong |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Inspire: Programming Materials Via Biomolecular Engineering @ Pennsylvania State Univ University Park
This INSPIRE award to University of Connecticut is partially funded by the Biomaterials program in the Division of Materials Research in the Directorate for Mathematical and Physical Sciences. The other three interdisciplinary programs that are partially funding this award are the Biosensor program and the Biotechnology, Biochemical, and Biomass Engineering program in the Division of Chemical, Bioengineering, Environmental, & Transport Systems, and the Materials for Surface Engineering program in the Division of Civil, Mechanical and Manufacturing Innovation. All these three programs are in the Directorate for Engineering. The objective of this project is to apply nature and biology as design guidelines in the creation of new generation of active materials. Over the years, the field of materials science has evolved from the study of inert materials to the design of active materials. However, current active materials usually need physical stimulation from light, temperature, ultrasound, electricity, and magnetism. These physical stimuli lack a high resolution controlled at the molecular level. Their reliance on complicated instruments and operations also limit the wide applications of active materials. The main thrust of this award will be is in developing programmable surfaces that can be used to change their properties on demand, and to produce materials with diverse but predetermined functions. As proof of the concept and to validate the hypotheses, the investigator will modify selected surfaces with two or more sets of oligonucleotides with specific and predetermined binding properties. Hybrid oligonucleotides with nanomaterial cargo-carrying drug (or enzymes or other functional materials) could be used to program the absorption and desorption and release the contents of nanomaterial cargo in the presence of a set of 'mutated' oligonucleotides on the surface. The mutated hybrid oligonucleotides could be altered based on the hybrid nucleotides with the nanomaterials cargo. The success of the proposed research holds great potential of transforming the way current and future materials are developed for various applications such as human healthcare and materials manufacturing. The scientific broader impact of this award will be in developing multifunctional and adoptive materials for potential applications such as surface processing, drug delivery, biosensing, catalysis among others. The broader impacts of this project will be promoted by diverse educational and outreach activities supported by this award. As part of this project, innovative, interdisciplinary, and in-depth course work will be offered to students at different levels to learn cutting-edge biomolecular engineering technologies. Research findings will be broadly disseminated through high-impact journals, prestigious conferences, and the internet.
Materials are important in virtually every aspect of our life. However, currently available materials do not have capabilities to flexibly change properties as a small octopus can do during its defense against predators. Therefore, the long-term goal of this project is to explore a revolutionary concept of developing materials that can change their properties in a way mimicking the behavior of living organisms. If successful, the proposed research will open a new avenue for the human being to learn from nature and to create smart materials not existing in nature. This project also involves diverse and well-designed education and outreach activities that will make broad impacts on the education of graduate, undergraduate, and K-12 students. For instance, interdisciplinary 'learn-and-seek' teams will be established for K-12 students to learn state-of-the-art biomolecular nanotechnology and to develop 21st century skills. Research findings will not only be presented to researchers in the academia, but also to the public through the internet and social networks.
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0.961 |
2015 — 2019 |
Wang, Yong |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Molecularly Regulated Release of Angiogenic Factors From Superporous Hydrogels @ Pennsylvania State University-Univ Park
? DESCRIPTION: Vascularization is important for the treatment of various ischemic diseases and the survival of tissue-engineered constructs. Thus, the development of angiogenesis strategies has continuously attracted great attention in various fields. However, the realization o successful angiogenesis is challenging, because vascular formation and maturation involve multiple growth factors at different stages. Moreover, while insufficient angiogenic factors do not induce effective angiogenesis, excess angiogenic factors can lead to the formation of defective and leaky blood vessels. Thus, therapeutic angiogenesis requires not only multiple growth factors, but also mechanisms for modulating the time, dosage, and sequential order of growth factor delivery. While bolus injections are the simplest way to control the time, dosage, and sequential order of growth factor delivery, this mode of delivery requires very high levels of growth factors. It can lead to severe systemic toxicity. By contrast, polymeric delivery systems hold great promise for localized delivery of growth factors with reduced systemic toxicity. However, it is challenging to develop a polymeric system to control the release time, dosage and sequential order of multiple growth factors. The objective of this application is to develop a novel molecularly controlled release mechanism and a hydrogel-based polymeric system that can release multiple angiogenic factors with differential and independent timing and dose control, hence regulating angiogenesis in a dynamic manner. The central hypothesis is that multiple growth factors would be sequestered within the same hydrogel by specific binding to hydrogel-linked nucleic acid aptamers, and released specifically by competitive binding of complementary sequence (CS) triggers. To test this hypothesis, we will work on three specific aims: 1) to synthesize aptamer-functionalized superporous hydrogels (AS-gels) for high-capacity sequestration and retention of multiple growth factors; 2) to design and optimize aptamer and CS sequences and to determine molecularly regulated growth factor release from AS-gels in vitro; and 3) to investigate molecularly regulated growth factor release from AS-gels and angiogenesis in mice. We have performed preliminary studies and acquired compelling data showing that AS-gels can sequester growth factors and release them in the presence of CS triggers. More importantly, AS-gels can be triggered to release growth factors to stimulate angiogenesis in vivo. Therefore, the accomplishment of this project will lead to a novel strategy for on-demand delivery of multiple growth factors. It will benefit the treatment of various ischemic diseases such as repair of internal organs where it is too harmful or impossible to repeatedly inject growth factors directly into the tissue.
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0.961 |
2015 — 2017 |
Song, Sheng-Kwei [⬀] Wang, Yong |
U01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Imaging Optic Nerve Function and Pathology
? DESCRIPTION (provided by applicant): The stated aspirational goal of the NEI, to Regenerate Neurons and Neural Connections in the Eye and Visual System, requires the development of modalities capable of non-invasively imaging neural connections as they are reestablished between the eye and the brain. In proof-of-concept studies we have introduced two promising techniques, diffusion basis spectrum imaging (DBSI) and diffusion functional magnetic resonance imaging (diffusion fMRI) for visualizing the pathology and function of the optic nerve in situ. In the current proposal, we will combine these technologies to deliver a new, diffusion MRI-based method to assess optic nerve anatomy, function and pathology simultaneously in both mice and human subjects. We will validate this approach by monitoring the progression and/or regression of axonal damage in glaucoma and optic neuritis. In keeping with the overall aspirations of the NEI, our long-term goal is to utilize this methodology to assess, non- invasively, the structure and function of regenerating axons in the optic nerve. Three specific aims will be pursued: (1) To quantify the relationships between diffusion MRI signals, axon number and visual function in an optic nerve crush mouse model, correlating DBSI with histological counts of axon number and diffusion fMRI with visual acuity; (2) To perform in vivo experiments and in silico computation (adapting structural information obtained from histology) on the optic nerve crush mouse model to identify a diffusion time optimized for both DBSI and diffusion fMRI and thus distinguish the contribution of restricted isotropic (distant from the axons) and anisotropic (adjacent to the axons) diffusion; and (3) To develop and optimize in vivo human optic nerve diffusion MRI protocol and visual stimulation paradigm that can simultaneously visualize optic nerve anatomy, function and pathology in glaucoma and optic neuritis patients. At completion, we will have established a novel imaging method to simultaneously assess optic nerve anatomy, function, and pathology allowing a detailed pathophysiological investigation of optic neuropathies.
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1 |
2017 — 2021 |
Benzinger, Tammie Lee Smith Wang, Yong |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Quantification of Neuroinflammation Inalzheimer's Disease Using Diffusion Basisspectrum Imaging
Project Summary/Abstract The Charles F. and Joanne Knight Alzheimer's Disease Research Center (Knight ADRC) at Washington University was founded as the Memory and Aging Project in 1979. Since that year, it has received continuous funding from the National Institutes of Health (NIH) and now supports an active cohort of nearly 800 participants who undergo longitudinal clinical and biomarker assessments for preclinical and symptomatic Alzheimer's disease (AD). The Knight ADRC is supported by three major NIH awards, the ADRC center grant (P50AG05681, JC Morris PI), the Healthy Aging and Senile Dementia (HASD; AG03991, JC Morris PI, Imaging Core Leader T Benzinger), and the Adult Children Study (ACS, P01 AG026276, JC Morris PI, Project 4 Leader T Benzinger). With this R01, we request funding for a new initiative which will add a novel biomarker of neuroinflammation in AD, diffusion basis spectrum imaging (DBSI) magnetic resonance imaging (MRI). Members of our research team have previously established the validity of DBSI MRI for neuroinflammation in multiple sclerosis, including both in vivo and ex vivo mouse and human studies. We now extend this research to AD, and will perform in vivo validation using positron emission tomography (PET) and ex vivo validation in human post mortem samples, including immunohistochemistry and autoradiography. Our preliminary data supports the predictive value of neuroinflammation markers in the progress from normal cognition to dementia, and in particularly, the promise of DBSI MRI for this, findings which we will validate in this larger study. We hypothesize that DBSI MRI will correspond to regional neuroinflammation in PET scans and that will correspond to areas of microglial infiltration in the autopsy specimens. We hypothesize that this relationship will be present in the earliest preclinical stages of AD, when cerebrospinal fluid (CSF) has abnormally low levels of A? but does not yet demonstrate abnormal levels of tau. Because DBSI MRI requires only Food and Drug Administration (FDA) approved MRI sequences, it could be rapidly extended to clinical trials or clinical populations.
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1 |
2018 — 2021 |
Cahill, Alison G. Wang, Yong |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Applying Diffusion Basis Spectrum Imaging to Characterize Human Placenta Immuno-Response During Normal Term and Preterm Pregcies
Summary/Abstract An important cause of preterm labor is immune infiltration into the placenta. Although the placental immune response likely starts long before delivery, no technique currently available permits in vivo, real-time assessment of placental immune responses during pregnancy. As a result, clinicians have limited ability to detect placental inflammation or intervene so as to reduce the immune response and prevent preterm delivery. This R01 application proposes to develop a novel, noninvasive human placental immune imaging (PII) technique, which will be able to safely assess human placental inflammation in real time, responding to RFA-HD-18-003: Moving Beyond Standard Assessments: Applying Novel Tools to Assess Human Placental Structure and Function in Real Time. PII will be based on a diffusion magnetic resonance imaging (MRI) technique called diffusion basis spectrum imaging, which can noninvasively image and quantify brain inflammation in multiple sclerosis in both animal models and human patients. Development of PII must take into account the fact that the human placenta is quite different from animal placentas and is a very dynamically changing organ throughout pregnancy. The anatomic and potential pathological complexity and heterogeneity of the placenta create strong background noise interference not present in the brain, making it more challenging to identify and extract the signals specific to placental inflammation. To address this technical challenge, this proposal will develop PII specifically for human applications by making use of three distinct clinical cohorts: those at low risk of preterm birth (Aim 1), and those at high risk of preterm birth who either respond or fail to respond to treatment to prevent preterm birth (Aims 2 and 3). In addition to performing PII on these women at two (Aims 2 and 3) or three (Aim 1) time points in pregnancy, this proposal includes measurement of immune factors and long non-coding RNAs in maternal blood, and histological characterization of inflammatory cells in placenta samples obtained at delivery. Completion of these aims will 1) yield a fully developed PII system, 2) refine PII through histopathological assessments of placentas and measures of systemic immune responses, 3) define the placental immune responses characteristic of healthy, term pregnancy, 4) identify placental immune responses characteristic of pregnancies at risk of preterm birth, and 5) begin to reveal immune signatures associated with success and failure of progesterone treatment. Because PII will require MRI sequences that are already approved by the Food and Drug Administration, its safety and great accessibility will allow it to be rapidly extended to clinical trials or clinical populations.
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1 |
2021 — 2025 |
Pfaendtner, W. James Wang, Yong Lin, Hongfei [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Efri E3p: a Novel Sequential Catalytic Solvolysis Process For Deconstructing Municipal Waste Plastics @ Washington State University
Municipal plastic solid wastes represent a large, untapped source of energy and chemicals. Upcycling discarded plastics into high-value products could result in economic savings of billions of dollars and minimize negative environmental impact. However, municipal plastic waste streams are a mixture of various incompatible polymers such as polyethylene, polypropylene, polyvinylchloride, polyethylene terephthalate, and polystyrene, as well as polymer additives, dyes, and contaminants. As a result, recovering high-quality plastic materials from mixed solid municipal wastes by physical sorting is a challenge. Thermochemical recycling of waste plastics is not economical since the current processes require intensive energy inputs and costly product upgrading. Therefore, energy-efficient catalytic deconstruction processes are needed to overcome the chemical and physical challenges of recycling mixed plastics. This project will develop an innovative waste plastics chemical upcycling process that selectively converts co-mingled waste plastics to valuable monomers and chemicals. It aims to promote a plastics circular economy and mitigate the negative environmental impact caused by accumulated plastic wastes. Education and outreach activities will be integrated with the research program to facilitate student and workforce development and encourage the participation of students from underrepresented groups in STEM.
The proposed waste plastics deconstruction approach is centered around the sequential catalytic solvolysis (SeCatSol) process. The SeCatSol process is a novel technology being developed at Washington State University for the selective stage-by-stage deconstruction of an individual polymer or classes of polymers in a polymer mixture using robust organocatalysts and heterogeneous catalysts under mild conditions. The SeCatSol process is designed to address the grand challenge in the plastic industry: how to deconstruct co-mingled municipal waste plastics selectively. The SeCatSol process sequentially produces monomers or value-added chemical products in each catalytic conversion unit, providing a feasible “Chemical Sorting” method to upcycle the complex municipal plastic mixtures at a molecular level. A systematic team effort aims at developing highly selective catalysts and efficient solvents for the SeCatSol process. In particular, the advanced in-situ and operando characterization tools, such as NMR, ATR-FTIR, and Raman spectroscopy, will decipher the complexity of deconstructing waste plastics. Furthermore, novel predictive molecular computational methods will accelerate catalyst design and solvent selection. The proposed technology framework fits into a circular economic model that is restorative and regenerative by design. This project represents the transformative work required for the significant advancement of fundamental polymer science and engineering knowledge.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
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