Patients afflicted with ulcerative colitis (UC) are at increased risk of colorectal cancer. While its causes are not fully understood, UC is associated with defects in colonic epithelial barriers that sustain inflammation of the colon mucosa caused by recruitment of lymphocytes and neutrophils into the lamina propria. Based on genetic evidence that attenuation of the bridging integrator 1 (Bin1) gene can limit UC pathogenicity in animals, we have explored Bin1 targeting as a therapeutic option. Early feasibility studies in the dextran sodium sulfate mouse model of experimental colitis showed that administration of a cell-penetrating Bin1 monoclonal antibody (Bin1 mAb 99D) could prevent lesion formation in the colon mucosa in part by preventing rupture of lymphoid follicles. In vivo administration of Bin1 mAb altered tight junction protein expression and cecal barrier function. Strikingly, electrophysiology studies in organ cultures showed that Bin1 mAb could elevate resistance and lower 14 Cmannitol leakage across the cecal mucosa, consistent with a direct strengthening of colonic barrier function. Transcriptomic analyses of colitis tissues highlighted altered expression of genes involved in circadian rhythm, lipid metabolism, and inflammation, with a correction of the alterations by Bin1 mAb treatment to patterns characteristic of normal tissues. Overall, our results suggest that Bin1 mAb protects against UC by directly improving colonic epithelial barrier function to limit gene expression and cytokine programs associated with colonic inflammation. K E Y W O R D S circadian rhythm, inflammatory bowel disease (IBD), immunotherapy, inflammation, tight junctions, ulcerative colitis (UC), Bin1 monoclonal antibody J Cell Biochem. 2019;120:4225-4237. wileyonlinelibrary.com/journal/jcb | 4225

This review discusses how the measurement of proteins in blood and its components via quantitative proteomics analyses can inform health status. Various external and internal factors such as environmental conditions, genetic background, nutrition, diet, and lifestyle, chronic pathological conditions, disease state, or therapeutic intervention will be investigated and their effects on the protein profile will be shown. The resulting changes to ones’ health and how this protein expression information can be used in early screening/diagnostic applications, drug discovery, precision treatment, patient management, and monitoring overall health status will also be presented.

Dried blood samples (DBSs) have many advantages; yet, impediments have limited the clinical utilization of DBSs. We developed a novel volumetric sampling device that collects a precise volume of blood, which overcomes the heterogeneity and hematocrit issues commonly encountered in a traditional DBS card collection as well as allowing for more efficient extraction and processing procedures and thus, more efficient quantitation, by using the entire sample. We also provided a thorough procedure validation using this volumetric DBS collection device with an established quantitative proteomics analysis method, and then analyzed 1000 proteins using this approach in DBSs concomitantly with serum for future consideration of utility in clinical applications. Our data provide a first step in the establishment of a DBS database for the broad application of this sample type for widespread use in clinical proteomic and other analyses applications.

Antibody arrays represent a high-throughput technique that enables the parallel detection of multiple proteins with minimal sample volume requirements. In recent years, antibody arrays have been widely used to identify new biomarkers for disease diagnosis or prognosis. Moreover, many academic research laboratories and commercial biotechnology companies are starting to apply antibody arrays in the field of drug discovery. In this review, some technical aspects of antibody array development and the various platforms currently available will be addressed; however, the main focus will be on the discussion of antibody array technologies and their applications in drug discovery. Aspects of the drug discovery process, including target identification, mechanisms of drug resistance, molecular mechanisms of drug action, drug side effects, and the application in clinical trials and in managing patient care, which have been investigated using antibody arrays in recent literature will be examined and the relevance of this technology in progressing this process will be discussed. Protein profiling with antibody array technology, in addition to other applications, has emerged as a successful, novel approach for drug discovery because of the well-known importance of proteins in cell events and disease development.