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Articles 1 - 16 of 16

Full-Text Articles in Biomedical Engineering and Bioengineering

Design And Synthesis Of Multivalent Α-1,2-Trimannose-Linked Bioerodible Microparticles For Applications In Immune Response Studies Of Leishmania Major Infection, Chelsea L. Rintelmann, Tara Grinnage-Pulley, Kathleen Ross, Daniel E. K. Kabotso, Angela Toepp, Anne Cowell, Christine Petersen, Balaji Narasimhan, Nicola Pohl Jan 2019

Design And Synthesis Of Multivalent Α-1,2-Trimannose-Linked Bioerodible Microparticles For Applications In Immune Response Studies Of Leishmania Major Infection, Chelsea L. Rintelmann, Tara Grinnage-Pulley, Kathleen Ross, Daniel E. K. Kabotso, Angela Toepp, Anne Cowell, Christine Petersen, Balaji Narasimhan, Nicola Pohl

Chemical and Biological Engineering Publications

Leishmaniasis, a neglected tropical disease, currently infects approximately 12 million people worldwide with 1 to 2 million new cases each year in predominantly underdeveloped countries. The treatment of the disease is severely underdeveloped due to the ability of the Leishmania pathogen to evade and abate immune responses. In an effort to develop anti-leishmaniasis vaccines and adjuvants, novel carbohydrate-based probes were made to study the mechanisms of immune modulation. In this study, a new bioerodible polyanhydride microparticle was designed and conjugated with a glycodendrimer molecular probe. This molecular probe incorporates a pathogen-like multivalent display of α-1,2-trimannose, for which a more ...


Interleukin-1 Alpha Increases Anti-Tumor Efficacy Of Cetuximab In Head And Neck Squamous Cell Carcinoma, Madelyn Espinosa-Cotton, Samuel N. Rodman Iii, Kathleen A. Ross, Isaac J. Jensen, Kenley Sangodeyi-Miller, Ayana J. Mclaren, Rachel A. Dahl, Katherine N. Gibson-Corley, Adam T. Koch, Yang-Xin Fu, Vladimir P. Badovinac, Douglas Laux, Balaji Narasimhan, Andrean L. Simons Jan 2019

Interleukin-1 Alpha Increases Anti-Tumor Efficacy Of Cetuximab In Head And Neck Squamous Cell Carcinoma, Madelyn Espinosa-Cotton, Samuel N. Rodman Iii, Kathleen A. Ross, Isaac J. Jensen, Kenley Sangodeyi-Miller, Ayana J. Mclaren, Rachel A. Dahl, Katherine N. Gibson-Corley, Adam T. Koch, Yang-Xin Fu, Vladimir P. Badovinac, Douglas Laux, Balaji Narasimhan, Andrean L. Simons

Chemical and Biological Engineering Publications

Background: Despite the high prevalence of epidermal growth factor receptor (EGFR) overexpression in head and neck squamous cell carcinomas (HNSCCs), incorporation of the EGFR inhibitor cetuximab into the clinical management of HNSCC has not led to significant changes in long-term survival outcomes. Therefore, the identification of novel therapeutic approaches to enhance the clinical efficacy of cetuximab could lead to improved long-term survival for HNSCC patients. Our previous work suggests that EGFR inhibition activates the interleukin-1 (IL-1) pathway via tumor release of IL-1 alpha (IL-1α), although the clinical implications of activating this pathway are unclear in the context of cetuximab therapy ...


Anticancer Drugs, Le Zhao, Zengyi Shao, Jacqueline V. Shanks Jan 2017

Anticancer Drugs, Le Zhao, Zengyi Shao, Jacqueline V. Shanks

Chemical and Biological Engineering Publications

Plant‐derived anticancer drugs play a large role in anticancer pharmaceuticals. Through reviewing the four major types of plant anticancer drugs, namely vinca alkaloids, taxane diterpenoids, podophyllotoxin lignans, and camptothecin quinoline alkaloids, this article illustrates the development process, current status, existing challenges, and future perspective of the plant anticancer drug production. Moreover, this review explains how various biotechnologies, from the mature elicitation strategy to the “omics” techniques that are still undergoing development, can be applied to address the challenges in improving the production of the plant‐sourced anticancer drugs.


Hemagglutinin-Based Polyanhydride Nanovaccines Against H5n1 Influenza Elicit Protective Virus Neutralizing Titers And Cell-Mediated Immunity, Kathleen Alaine Ross, Hyelee Park Loyd, Wuwei Wu, Lucas Mark Huntimer, Shaheen Ahmed, Anthony Sambol, Scott Broderick, Zachary Flickinger, Krishna Rajan, Tatiana Bronich, Surya K. Mallapragada, Michael J. Wannemuehler, Susan Long Carpenter, Balaji Narasimhan Jan 2015

Hemagglutinin-Based Polyanhydride Nanovaccines Against H5n1 Influenza Elicit Protective Virus Neutralizing Titers And Cell-Mediated Immunity, Kathleen Alaine Ross, Hyelee Park Loyd, Wuwei Wu, Lucas Mark Huntimer, Shaheen Ahmed, Anthony Sambol, Scott Broderick, Zachary Flickinger, Krishna Rajan, Tatiana Bronich, Surya K. Mallapragada, Michael J. Wannemuehler, Susan Long Carpenter, Balaji Narasimhan

Chemical and Biological Engineering Publications

H5N1 avian influenza is a significant global concern with the potential to become the next pandemic threat. Recombinant subunit vaccines are an attractive alternative for pandemic vaccines compared to traditional vaccine technologies. In particular, polyanhydride nanoparticles encapsulating subunit proteins have been shown to enhance humoral and cell-mediated immunity and provide protection upon lethal challenge. In this work, a recombinant H5 hemagglutinin trimer (H53) was produced and encapsulated into polyanhydride nanoparticles. The studies performed indicated that the recombinant H53 antigen was a robust immunogen. Immunizing mice with H53 encapsulated into polyanhydride nanoparticles induced high neutralizing antibody titers and enhanced CD4+ T ...


Matrix Metalloproteinase-14 Is A Mechanically Regulated Activator Of Secreted Mmps And Invasion, Amanda Haage, Dong Hyun Nam, Xin Ge, Ian C. Schneider Jul 2014

Matrix Metalloproteinase-14 Is A Mechanically Regulated Activator Of Secreted Mmps And Invasion, Amanda Haage, Dong Hyun Nam, Xin Ge, Ian C. Schneider

Chemical and Biological Engineering Publications

Matrix metalloproteinases (MMPs) are extracellular matrix (ECM) degrading enzymes and have complex and specific regulation networks. This includes activation interactions, where one MMP family member activates another. ECM degradation and MMP activation can be initiated by several different stimuli including changes in ECM mechanical properties or intracellular contractility. These mechanical stimuli are known enhancers of metastatic potential. MMP-14 facilitates local ECM degradation and is well known as a major mediator of cell migration, angiogenesis and invasion. Recently, function blocking antibodies have been developed to specifically block MMP-14, providing a useful tool for research as well as therapeutic applications. Here we ...


A Systems Approach To Designing Next Generation Vaccines: Combining α-Galactose Modified Antigens With Nanoparticle Platforms, Yashdeep Phanse, Brenda Rocio Carrillo-Conde, Amanda Ellen Ramer-Tait, Scott Broderick, Chang Sun Kong, Krishna Rajan, Ramon Flick, Robert B. Mandell, Balaji Narasimhan, Michael J. Wannemuehler Jan 2014

A Systems Approach To Designing Next Generation Vaccines: Combining α-Galactose Modified Antigens With Nanoparticle Platforms, Yashdeep Phanse, Brenda Rocio Carrillo-Conde, Amanda Ellen Ramer-Tait, Scott Broderick, Chang Sun Kong, Krishna Rajan, Ramon Flick, Robert B. Mandell, Balaji Narasimhan, Michael J. Wannemuehler

Chemical and Biological Engineering Publications

Innovative vaccine platforms are needed to develop effective countermeasures against emerging and re-emerging diseases. These platforms should direct antigen internalization by antigen presenting cells and promote immunogenic responses. This work describes an innovative systems approach combining two novel platforms, αGalactose (αGal)-modification of antigens and amphiphilic polyanhydride nanoparticles as vaccine delivery vehicles, to rationally design vaccine formulations. Regimens comprising soluble αGal-modified antigen and nanoparticle-encapsulated unmodified antigen induced a high titer, high avidity antibody response with broader epitope recognition of antigenic peptides than other regimen. Proliferation of antigen-specific CD4 + T cells was also enhanced compared to a traditional ...


Multiple-Input Subject-Specific Modeling Of Plasma Glucose Concentration For Feedforward Control, Kaylee Renee Kotz, Ali Cinar, Yong Mei, Amy Roggendorf, Elizabeth Littlejohn, Laurie Quinn, Derrick K. Rollins Sr. Jan 2014

Multiple-Input Subject-Specific Modeling Of Plasma Glucose Concentration For Feedforward Control, Kaylee Renee Kotz, Ali Cinar, Yong Mei, Amy Roggendorf, Elizabeth Littlejohn, Laurie Quinn, Derrick K. Rollins Sr.

Chemical and Biological Engineering Publications

The ability to accurately develop subject-specific, input causation models, for blood glucose concentration (BGC) for large input sets can have a significant impact on tightening control for insulin dependent diabetes. More specifically, for Type 1 diabetics (T1Ds), it can lead to an effective artificial pancreas (i.e., an automatic control system that delivers exogenous insulin) under extreme changes in critical disturbances. These disturbances include food consumption, activity variations, and physiological stress changes. Thus, this paper presents a free-living, outpatient, multiple-input, modeling method for BGC with strong causation attributes that is stable and guards against overfitting to provide an e ffective ...


Combinatorial Evaluation Of In Vivo Distribution Of Polyanhydride Particle-Based Platforms For Vaccine Delivery, Latrisha K. Petersen, Lucas Mark Huntimer, Katharine Walz, Amanda Ellen Ramer-Tait, Michael J. Wannemuehler, Balaji Narasimhan Jan 2013

Combinatorial Evaluation Of In Vivo Distribution Of Polyanhydride Particle-Based Platforms For Vaccine Delivery, Latrisha K. Petersen, Lucas Mark Huntimer, Katharine Walz, Amanda Ellen Ramer-Tait, Michael J. Wannemuehler, Balaji Narasimhan

Chemical and Biological Engineering Publications

Several challenges are associated with current vaccine strategies, including repeated immunizations, poor patient compliance, and limited approved routes for delivery, which may hinder induction of protective immunity. Thus, there is a need for new vaccine adjuvants capable of multi-route administration and prolonged antigen release at the site of administration by providing a depot within tissue. In this work, we designed a combinatorial platform to investigate the in vivo distribution, depot effect, and localized persistence of polyanhydride nanoparticles as a function of nanoparticle chemistry and administration route. Our observations indicated that the route of administration differentially affected tissue residence times. All ...


Hypoglycemia Early Alarm Systems Based On Multivariable Models, Kamuran Turksoy, Elif S. Bayrak, Lauretta Quinn, Elizabeth Littlejohn, Derrick K. Rollins Sr., Ali Cinar Jan 2013

Hypoglycemia Early Alarm Systems Based On Multivariable Models, Kamuran Turksoy, Elif S. Bayrak, Lauretta Quinn, Elizabeth Littlejohn, Derrick K. Rollins Sr., Ali Cinar

Chemical and Biological Engineering Publications

Hypoglycemia is a major challenge of artificial pancreas systems and a source of concern for potential users and parents of young children with Type 1 diabetes (T1D). Early alarms to warn of the potential of hypoglycemia are essential and should provide enough time to take action to avoid hypoglycemia. Many alarm systems proposed in the literature are based on interpretation of recent trends in glucose values. In the present study, subject-specific recursive linear time series models are introduced as a better alternative to capture glucose variations and predict future blood glucose concentrations. These models are then used in hypoglycemia early ...


Mixed-Surface, Lipid-Tethered Quantum Dots For Targeting Cells And Tissues, Yanjie Zhang, Amanda Haage, Elizabeth M. Whitley, Ian C. Schneider, Aaron R. Clapp Jun 2012

Mixed-Surface, Lipid-Tethered Quantum Dots For Targeting Cells And Tissues, Yanjie Zhang, Amanda Haage, Elizabeth M. Whitley, Ian C. Schneider, Aaron R. Clapp

Chemical and Biological Engineering Publications

Quantum dots (QDs), with their variable luminescent properties, are rapidly transcending traditional labeling techniques in biological imaging and hold vast potential for biosensing applications. An obstacle in any biosensor development is targeted specificity. Here we report a facile procedure for creating QDs targeted to the cell membrane with the goal of cell-surface protease biosensing. This procedure generates water-soluble QDs with variable coverage of lipid functional groups. The resulting hydrophobicity is quantitatively controlled by the molar ratio of lipids per QD. Appropriate tuning of the hydrophobicity ensures solubility in common aqueous cell culture media and while providing affinity to the lipid ...


Analyzing Cellular Internalization Of Nanoparticles And Bacteria By Multi-Spectral Imaging Flow Cytometry., Yashdeep Phanse, Amanda Ellen Ramer-Tait, Sherree L. Friend, Brenda Rocio Carrillo-Conde, Paul A. Lueth, Carrie Jo Oster, Gregory J. Phillips, Balaji Narasimhan, Michael J. Wannemuehler, Bryan H. Bellaire Jun 2012

Analyzing Cellular Internalization Of Nanoparticles And Bacteria By Multi-Spectral Imaging Flow Cytometry., Yashdeep Phanse, Amanda Ellen Ramer-Tait, Sherree L. Friend, Brenda Rocio Carrillo-Conde, Paul A. Lueth, Carrie Jo Oster, Gregory J. Phillips, Balaji Narasimhan, Michael J. Wannemuehler, Bryan H. Bellaire

Chemical and Biological Engineering Publications

Nanoparticulate systems have emerged as valuable tools in vaccine delivery through their ability to efficiently deliver cargo, including proteins, to antigen presenting cells. Internalization of nanoparticles (NP) by antigen presenting cells is a critical step in generating an effective immune response to the encapsulated antigen. To determine how changes in nanoparticle formulation impact function, we sought to develop a high throughput, quantitative experimental protocol that was compatible with detecting internalized nanoparticles as well as bacteria. To date, two independent techniques, microscopy and flow cytometry, have been the methods used to study the phagocytosis of nanoparticles. The high throughput nature of ...


Harvesting Murine Alveolar Macrophages And Evaluating Cellular Activation Induced By Polyanhydride Nanoparticles., Ana Vianey Chavez-Santoscoy, Lucas Mark Huntimer, Amanda Ellen Ramer-Tait, Michael J. Wannemuehler, Balaji Narasimhan Jun 2012

Harvesting Murine Alveolar Macrophages And Evaluating Cellular Activation Induced By Polyanhydride Nanoparticles., Ana Vianey Chavez-Santoscoy, Lucas Mark Huntimer, Amanda Ellen Ramer-Tait, Michael J. Wannemuehler, Balaji Narasimhan

Chemical and Biological Engineering Publications

Biodegradable nanoparticles have emerged as a versatile platform for the design and implementation of new intranasal vaccines against respiratory infectious diseases. Specifically, polyanhydride nanoparticles composed of the aliphatic sebacic acid (SA), the aromatic 1,6-bis(p-carboxyphenoxy)hexane (CPH), or the amphiphilic 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) display unique bulk and surface erosion kinetics and can be exploited to slowly release functional biomolecules (e.g., protein antigens, immunoglobulins, etc.) in vivo. These nanoparticles also possess intrinsic adjuvant activity, making them an excellent choice for a vaccine delivery platform. In order to elucidate the mechanisms governing the activation of innate immunity ...


Amphiphilic Polyanhydride Nanoparticles Stabilize Bacillus Anthracis Protective Antigen, L. K. Petersen, Yashdeep Phanse, Amanda Ellen Ramer-Tait, Michael J. Wannemuehler, Balaji Narasimhan Jan 2012

Amphiphilic Polyanhydride Nanoparticles Stabilize Bacillus Anthracis Protective Antigen, L. K. Petersen, Yashdeep Phanse, Amanda Ellen Ramer-Tait, Michael J. Wannemuehler, Balaji Narasimhan

Chemical and Biological Engineering Publications

Advancements toward an improved vaccine against Bacillus anthracis, the causative agent of anthrax, have focused on formulations composed of the protective antigen (PA) adsorbed to aluminum hydroxide. However, due to the labile nature of PA, antigen stability is a primary concern for vaccine development. Thus, there is a need for a delivery system capable of preserving the immunogenicity of PA through all the steps of vaccine fabrication, storage, and administration. In this work, we demonstrate that biodegradable amphiphilic polyanhydride nanoparticles, which have previously been shown to provide controlled antigen delivery, antigen stability, immune modulation, and protection in a single dose ...


Design Of A Protective Single-Dose Intranasal Nanoparticle-Based Vaccine Platform For Respiratory Infectious Diseases, Bret Daniel Ulery, Devender Kumar, Amanda Ellen Ramer-Tait, Dennis W. Metzger, Michael J. Wannemuehler, Balaji Narasimhan Jan 2011

Design Of A Protective Single-Dose Intranasal Nanoparticle-Based Vaccine Platform For Respiratory Infectious Diseases, Bret Daniel Ulery, Devender Kumar, Amanda Ellen Ramer-Tait, Dennis W. Metzger, Michael J. Wannemuehler, Balaji Narasimhan

Chemical and Biological Engineering Publications

Despite the successes provided by vaccination, many challenges still exist with respect to controlling new and re-emerging infectious diseases. Innovative vaccine platforms composed of adaptable adjuvants able to appropriately modulate immune responses, induce long-lived immunity in a single dose, and deliver immunogens in a safe and stable manner via multiple routes of administration are needed. This work describes the development of a novel biodegradable polyanhydride nanoparticle-based vaccine platform administered as a single intranasal dose that induced long-lived protective immunity against respiratory disease caused by Yesinia pestis, the causative agent of pneumonic plague. Relative to the responses induced by the recombinant ...


Rational Design Of Pathogen-Mimicking Amphiphilic Materials As Nanoadjuvants, Bret Daniel Ulery, Latrisha K. Petersen, Yashdeep Phanse, Chang Sun Kong, Scott Broderick, Devender Kumar, Amanda Ellen Ramer-Tait, Brenda Rocio Carrillo-Conde, Krishna Rajan, Michael J. Wannemuehler, Bryan H. Bellaire, Dennis W. Metzger, Balaji Narasimhan Jan 2011

Rational Design Of Pathogen-Mimicking Amphiphilic Materials As Nanoadjuvants, Bret Daniel Ulery, Latrisha K. Petersen, Yashdeep Phanse, Chang Sun Kong, Scott Broderick, Devender Kumar, Amanda Ellen Ramer-Tait, Brenda Rocio Carrillo-Conde, Krishna Rajan, Michael J. Wannemuehler, Bryan H. Bellaire, Dennis W. Metzger, Balaji Narasimhan

Chemical and Biological Engineering Publications

An opportunity exists today for cross-cutting research utilizing advances in materials science, immunology, microbial pathogenesis, and computational analysis to effectively design the next generation of adjuvants and vaccines. This study integrates these advances into a bottom-up approach for the molecular design of nanoadjuvants capable of mimicking the immune response induced by a natural infection but without the toxic side effects. Biodegradable amphiphilic polyanhydrides possess the unique ability to mimic pathogens and pathogen associated molecular patterns with respect to persisting within and activating immune cells, respectively. The molecular properties responsible for the pathogen-mimicking abilities of these materials have been identified. The ...


Mannose-Functionalized "Pathogen-Like" Polyanhydride Nanoparticles Target C-Type Lectin Receptors On Dendritic Cells, Brenda Rocio Carrillo-Conde, Eun-Ho Song, Ana Vianey Chavez-Santoscoy, Yashdeep Phanse, Amanda Ellen Ramer-Tait, Nicola L.B. Pohl, Michael J. Wannemuehler, Bryan H. Bellaire, Balaji Narasimhan Jan 2011

Mannose-Functionalized "Pathogen-Like" Polyanhydride Nanoparticles Target C-Type Lectin Receptors On Dendritic Cells, Brenda Rocio Carrillo-Conde, Eun-Ho Song, Ana Vianey Chavez-Santoscoy, Yashdeep Phanse, Amanda Ellen Ramer-Tait, Nicola L.B. Pohl, Michael J. Wannemuehler, Bryan H. Bellaire, Balaji Narasimhan

Chemical and Biological Engineering Publications

Targeting pathogen recognition receptors on dendritic cells (DCs) offers the advantage of triggering specific signaling pathways to induce a tailored and robust immune response. In this work, we describe a novel approach to targeted antigen delivery by decorating the surface of polyanhydride nanoparticles with specific carbohydrates to provide "pathogen-like" properties that ensure nanoparticles engage C-type lectin receptors on DCs. The surface of polyanhydride nanoparticles was functionalized by covalent linkage of dimannose and lactose residues using an amine-carboxylic acid coupling reaction. Coculture of functionalized nanoparticles with bone marrow-derived DCs significantly increased cell surface expression of MHC II, the T cell costimulatory ...