Instrumented Tissue-in-a-Chip: A Bridge from In Vitro to In Vivo
Professor Chuck Henry | Colorado State University
Hosted by Professor Rebecca Pompano
Microfluidic methods provide a promising path to mimicking human organ function with applications ranging from fundamental biology to drug metabolism and toxicity. The vast majority of these systems use dissociated, immortalized, or stem cells to create two and three-dimensional models in vitro. While these systems can provide valuable information, they are fundamentally incapable of recreating the three-dimensional complexity of real tissue. As a result, an important gap exists between in vitro models and in vivo systems. To address this gap, we have begun combining microfluidic devices with ex vivo tissue slices or explants to recreate model systems that capture the cellular diversity of real tissue and bridge the gap between in vitro models and in vivo systems. In this presentation two systems will be discussed. The first uses a high-density electrode array equipped with microfluidic flow to image chemical release profiles from living adrenal slices. The second uses a 3D printed microfluidic device with removable inserts to hold and perfuse fluids over intestinal tissue, enabling generation of differential chemical conditions on either side of this important barrier tissue.
Charles Henry, Stuart Tobet, David Dandy, Tom Chen
Colorado State University
New Chemical Probe Technologies: Applications to Imaging, Target Identification and Drug Discovery
Professor Matthew Bogyo | Stanford University
Hosted by Professor Ken Hsu
Hydrolases are enzymes that often play important roles in many common human diseases such as cancer, asthma, arthritis, atherosclerosis and infection by pathogens. Therefore tools that can be used to dynamically monitor their activity can be used as diagnostic agents, as imaging contrast agents and for the identification of novel classes of drugs. In the first part of this presentation, I will describe our efforts to design and synthesize small molecule probes that produce a fluorescent signal upon binding to tumor associated protease targets. We have identified probes that show tumor-specific retention, fast activation kinetics, and rapid systemic distribution making them useful for real-time fluorescence guided tumor resection and other diagnostic imaging applications. In the second half of the talk, I will present our recent advances using chemical probes to identify novel protease and hydrolase targets in pathogenic bacteria. This work has led to new imaging agents for Mycobacterium tuberculosis and the identification of novel virulence factors in Staphylococcus aureus that have the potential to be targeted with small molecules as a therapeutic strategy.
Chemistry and Biology of Nucleic Acid- and Nucleotide-Binding Proteins
Professor Yinsheng Wang | University of California Riverside
Hosted by Professor Huiwang Ai
The functions of nucleotides and nucleic acids involve their interactions with cellular proteins. In this presentation, I will discuss about our recent efforts toward the development and applications of quantitative proteomic methods for unbiased, proteome-wide discovery of proteins that can recognize unique secondary structures of DNA. I will also discuss our recent development of targeted quantitative proteomic methods for interrogating ATP- and GTP-binding proteins at the entire proteome scale. The application of these methods for uncovering novel targets of clinically used kinase inhibitors and for revealing novel drivers and suppressors for melanoma metastasis will also be presented. Through this presentation, I hope to illustrate that quantitative proteomics constitutes a power tool for discovering novel nucleic acid- and nucleotide-binding proteins and for revealing their functions in cells.
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