200 Years of The Haloform Reaction: Methods and Applications.

Discovered in 1822, the haloform reaction is one of the oldest synthetic organic reactions. The haloform reaction enables the synthesis of carboxylic acids, esters or amides from methyl ketones. The reaction proceeds via exhaustive α-halogenation and then substitution by a nucleophile to liberate a haloform.

Isoelectric point (pI)-based phase separation (pI-BPS) purification of elastin-like polypeptides (ELPs) containing charged, biologically active fusion proteins (ELP-FPs).

Elastin-like polypeptides (ELPs) are peptide-based biomaterials with residue sequence (VPGXG)n where X is any residue except proline. ELPs are a useful modality for delivering biologically active proteins (growth factors, protease inhibitors, anti-inflammatory peptides, etc.) as fusion proteins (ELP-FP).

Investigating the Variation of Benzene and 1,3-Butadiene in the UK during 2000-2020.

The concentrations of benzene and 1,3-butadiene in urban, suburban, and rural sites of the U.K. were investigated across 20 years (2000-2020) to assess the impacts of pollution control strategies.

Origin, toxicity and characteristics of two amyloid oligomer polymorphs.

There is compelling evidence that small oligomeric aggregates, emerging during the assembly of amyloid fibrils and plaques, are important molecular pathogens in many amyloid diseases. While significant progress has been made in revealing the mechanisms underlying fibril growth, understanding how amyloid oligomers fit into the fibril assembly process, and how they contribute to the pathogenesis of amyloid diseases, has remained elusive. Commonly, amyloid oligomers are considered to be metastable, early-stage precursors to fibril formation that are either on- or off-pathway from fibril growth.

Hybrid fusion protein as a dual protease inhibitor for the healing of chronic wounds.

Diseases bring about the need for interventions that pinpoint each specific aspect of the illness. Commonly, remission of a complex disease is accomplished by mixing treatments, medications, and therapeutics together in a fashion where they may negatively interact with each other or never arrive at the diseased site as a systemic heterogeneous mixture. Chronic wounds display intricacy as they are very localized and have their own environment where tissue deconstruction due to high levels of numerous proteases outweighs normal tissue reconstruction.

Protease-Resistant Growth Factor Formulations for the Healing of Chronic Wounds.

Chronic wounds are long-term nonhealing wounds that are refractory to treatment. These wounds can present elevated protease levels, leading to rapid degradation of native and exogenously added growth factors. This work focused on developing a protease-resistant growth factor formulation for treatment of chronic wounds presented with high protease activity.

Plasmono-magnetic material for precise photothermal heating.

Noble metal nanoparticles have been extensively studied as photo-sensitive agents for photothermal cancer therapy. Precise control over the size and shape of the nanoparticles allowed strong optical absorption and efficient heat generation necessary for destroying a tumor to be achieved. However, one of the fundamental challenges of application of the nanoparticles towards photothermal cancer therapy is low specificity in the targeting tumor tissue in comparison with the healthy tissue and the resulting unfavorable biodistribution of the nanoparticles.

Growth factor functionalized biomaterial for drug delivery and tissue regeneration.

Elastin like polypeptides (ELPs) are a class of naturally derived and non-immunogenic biomaterials that are widely used in drug delivery and tissue engineering. ELPs undergo temperature-mediated inverse phase transitioning, which allows them to be purified in a relatively simple manner from bacterial expression hosts. Being able to genetically encode ELPs allows for the incorporation of bioactive peptides thereby functionalizing them.

Recombinant elastin-based nanoparticles for targeted gene therapy.

Among viruses, lentiviral vectors have been popular vectors for gene delivery due to their efficient mode of gene delivery. However, the nonspecific delivery of genes associated with lentiviral vectors may result in undesirable side effects. Here we propose a heterogeneous nanoparticle (NP) delivery system for targeted delivery of lentiviral particles containing a therapeutic gene.

Dynamic visualization of photothermal heating by gold nanocages using thermoresponsive elastin like polypeptides.

Understanding how plasmonic nanoparticles collectively generate heat upon exposure to light and thus increase the local temperature of the surrounding medium is critical for many applications such as plasmon-assisted microfluidics, plasmonic tweezers, and photothermal cancer therapy. Reliable temperature manipulation requires the capability to spatially and dynamically analyze local temperature profiles as a function of nanoparticle concentration and laser intensity. In this work, we present a novel method for visualization of local temperature increase using elastin-like polypeptides (ELP).

Elastin-like-polypeptide based fusion proteins for osteogenic factor delivery in bone healing.

Modern treatments of bone injuries and diseases are becoming increasingly dependent on the usage of growth factors to stimulate bone growth. Bone morphogenetic protein-2 (BMP-2), a potent osteogenic inductive protein, exhibits promising results in treatment models, but recently has had its practical efficacy questioned due to the lack of local retention, ectopic bone formation, and potentially lethal inflammation. Where a new delivery technique of the BMP-2 is necessary, here we demonstrate the viability of an elastin-like peptide (ELP) fusion protein containing BMP-2 for delivery of the BMP-2.

Expression and Purification of Neurotrophin-Elastin-Like Peptide Fusion Proteins for Neural Regeneration.

Background: Neural injuries such as spinal cord injuries, traumatic brain injuries, or nerve transection injuries pose a major health problem. Neurotrophins such as nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF) have been shown to improve the outcome of neural injuries in several pre-clinical models, but their use in clinics is limited by the lack of a robust delivery system that enhances their bioavailability and half-life.

Objectives: We describe two fusion proteins comprising NGF or BDNF fused with elastin-like peptides (ELPs).

Proliferative activity of elastin-like-peptides depends on charge and phase transition.

Elastin-like-peptides (ELPs) are stimulus-responsive protein-based polymers and are attractive biomaterials due to their biocompatibility and unique properties. This study shows that in addition to their physical properties, ELPs have biological activities that are conducive to tissue regeneration. Specifically, we found that ELPs induce fibroblast proliferation via cell surface heparan sulfate proteoglycans (HSPG).

Leveraging growth factor induced macropinocytosis for targeted treatment of lung cancer.

Targeted therapy focused on highly expressed growth factor receptors is increasingly becoming popular for the treatment of lung cancer. Cancer cells exhibit higher levels of macropinocytosis than the normally quiescent non-cancerous cells, which can further be enhanced by growth factors. Here, we show the targeted enhancement of macropinocytosis in lung cancer cells for the delivery of the mitochondriotoxic peptide (KLAKLAK)2 using keratinocyte growth factor (KGF).

MICROFLUIDIC DEVICE FOR EXAMINING DIRECTIONAL SENSING IN DENDRITIC CELL CHEMOTAXIS.

Dendritic cell chemotaxis is an important process involved in the acquisition of adaptive immunity. Despite several studies, our understanding of this process remains limited. One of the reasons for this is the lack of experimental models that give us real-time information on dendritic cell locomotion.

Delivery of growth factors for tissue regeneration and wound healing.

Growth factors are soluble secreted proteins capable of affecting a variety of cellular processes important for tissue regeneration. Consequently, the self-healing capacity of patients can be augmented by artificially enhancing one or more processes important for healing through the application of growth factors. However, their application in clinics remains limited due to lack of robust delivery systems and biomaterial carriers.

Synergistic administration of photothermal therapy and chemotherapy to cancer cells using polypeptide-based degradable plasmonic matrices.

Aim: Resistance of cancer cells to hyperthermic temperatures and spatial limitations of nanoparticle-induced hyperthermia necessitates the identification of effective combination treatments that can enhance the efficacy of this treatment. Here we show that novel polypeptide-based degradable plasmonic matrices can be employed for simultaneous administration of hyperthermia and chemotherapeutic drugs as an effective combination treatment that can overcome cancer cell resistance to hyperthermia.

Method: Novel gold nanorod elastin-like polypeptide matrices were generated and characterized.

Microfluidics for T- lymphocyte cell separation and inflammation monitoring in burn patients.

Severe burns result in T lymphocyte specific immunologic changes. In addition to decreased levels of circulating lymphocytes, changes in cytokine secretion and receptor expression also take place. Our finer understanding of the inflammatory response has led to the development of immune-targeted therapeutics, requiring specialized gene-expression monitoring.

Self-assembling elastin-like peptides growth factor chimeric nanoparticles for the treatment of chronic wounds.

Chronic wounds are associated with poor epidermal and dermal remodeling. Previous work has shown the efficacy of keratinocyte growth factor (KGF) in reepithelialization and elastin in dermal wound healing. Here we demonstrate the fabrication of a fusion protein comprising of elastin-like peptides and KGF.

JNK regulates binding of alpha-catenin to adherens junctions and cell-cell adhesion.

We recently reported that c-Jun N-terminal kinase (JNK) is associated with adherens junctions and phosphorylates β-catenin at serine 33/37 and threonine 41. Here, we report that inhibition of JNK led to formation of adherens junctions, which was accompanied by dissociation of α-catenin from the β-catenin/E-cadherin complex and increased association of α-catenin with the cytoskeleton. Conversely, activation of JNK increased binding of α-catenin to β-catenin, which was blocked by the JNK inhibitor SP600125 or JNK siRNA.

JNK phosphorylates beta-catenin and regulates adherens junctions.

The c-Jun amino-terminal kinase (JNK) is an important player in inflammation, proliferation, and apoptosis. More recently, JNK was found to regulate cell migration by phosphorylating paxillin. Here, we report a novel role of JNK in cell adhesion.

Optically responsive gold nanorod-polypeptide assemblies.

Environmentally responsive nanoassemblies based on polypeptides and nanoparticles can have a number of promising biological/biomedical applications. We report the generation of gold nanorod (GNR)-elastin-like polypeptide (ELP) nanoassemblies whose optical response can be manipulated based on exposure to near-infrared (NIR) light. Cysteine-containing ELPs were self-assembled on GNRs mediated by gold-thiol bonds, leading to the generation of GNR-ELP nanoassemblies.

KGF promotes integrin alpha5 expression through CCAAT/enhancer-binding protein-beta.

Keratinocyte growth factor (KGF) and alpha(5)beta(1)-integrin are not expressed in normal skin but they are both highly upregulated in the migrating epidermis during wound healing. Here we report that KGF increased alpha(5) mRNA and protein levels in epidermoid carcinoma cells and stratified bioengineered epidermis. Interestingly, KGF increased integrin alpha(5) in the basal as well as suprabasal cell epidermal layers.

Epidermal morphogenesis: the transcriptional program of human keratinocytes during stratification.

The epidermis serves to protect the body against environmental assaults and at the same time is able to survive and replenish itself under harsh conditions. The epidermis accomplishes this feat via a well-orchestrated program of stratification and terminal differentiation that provides barrier against infection, radiation, and water loss. Despite significant progress in skin biology, many molecules and pathways that are involved in stratification and barrier formation remain unknown.