Life & Health Sciences

Prof. Livio Casarini

Dr Abhishek Baghela

Prof. Alfredo Ulloa-Aguirre

Prof. Stephen Foster

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Development of novel chemoselective ligation techniques for protein chemical synthesis


ABSTRACT

A novel strategy has been devised that allows a ligation of of thioacids and imidazolyl urea activated amines under aqueous conditions. This approach enables the traceless removal of imidazole and CO2 to directly generate the desired amide bond without affecting the side chain reactive side chain functional groups on the peptide chain. Meanwhile, the novel synthesis of peptide thioacid is also reported.  

 

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Targeting periostin reduces inflammation and respiratory barrier injury in lung diseases.


ABSTRACT

Periostin (POSTN) is a matricellular protein that plays a key role in development and repair within the biological matrix of the lung. POSTN is highly expressed in several cell types in lung such as epithelial or endothelial cells, fibroblasts, smooth muscle and mast cells, contributing to mucus secretion, alveolar epithelial repair, and lung fibrosis. However, the underlying mechanism how POSTN contributes to the development of lung inflammation remains unclear. In the current study, we attempted to determine whether treatment with a monoclonal anti-POSTN antibody induces a significant inhibition of asthmatic reactions in a mouse asthma model. Mice sensitized and challenged with papain evidenced an increased periostin expression in lung and typical asthmatic reactions, as follows: an increase in the number of eosinophils in bronchoalveolar lavage fluid; a marked influx of inflammatory cells into the lung around blood vessels and airways, and Th2 cytokines including IL-4 and IL-5 and chemokines in the bronchoalveolar lavage (BAL) fluid; emphysema; the detection of thymic stromal lymphopoietin (TSLP) produced by epithelial cells. However, the administration of anti-POSTN prior to the final airway papain challenge resulted in a significant inhibition of all asthmatic reactions. We also demonstrated that anti-POSTN antibody treatment resulted in significant reductions on collagen expression and a reduction in the increased eosinophil. The treatment of animals with anti-POSTN resulted in a significant reduction in the concentrations of the chemokines (CCL-11 and CCL-17) in the airways, without any concomitant increase in the concentration of Th1 cytokines. This study identifies a novel therapeutic strategy for airway hyperresponsiveness, which uses antibodies reactive against POSTN via the inhibition of the Th2 response. It also provides theoretical evidence for the control of allergic asthma and fibrosis by targeting POSTN.


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Responsive Nanozeolites: Smart Porosity and Surface Tailoring for Multimodal Imaging and Therapy of Cancer


ABSTRACT

Effective cancer treatment requires its early diagnosis in combination with safe drug delivery mechanisms. Up to date many therapeutics have failed due to their limited ability to reach the diseased site selectively without damaging healthy cells. Furthermore, none of the existing imaging techniques is absolutely reliable due to the differences in resolution and sensitivity. Therefore, synergistic combination of imaging modalities in one, typically nanodimensional, probe is the key-strategy  to benefit from, for example the sensitive and quantifiable PET signal and the high resolution of MRI. Nanozeolites are among the most promising candidates for realization of this concept due to their unique crystalline structure capable of stable hosting of metal-ions with diagnostic and therapeutic properties. Even though, these materials have found many applications in various technologies, their medicinal potential still requires thorough investigations. This project aimed at the design, preparation and testing of novel nanozeolitic probes that can be applied as personalized drugs for diagnostic and therapeutic purposes


Prof. Rita Singh

Dr Peggy L. Carver

Prof. Vincent Pecoraro