Characterization of Oral Gut-Selective vs. Systemic JAK Inhibitors in the Mouse Oxazolone Colitis Model

Drug Discovery and Development, Laboratory Technology, Life Sciences, Preclinical,
  • Tuesday, December 18, 2018 | 12:30pm EST (9:30am PST)
  • 60 min

Autoimmune diseases such as ulcerative colitis require chronic treatment that often causes systemic immunosuppression, increasing long term cancer and infection risk. Reducing systemic side effects with localized treatment would greatly benefit patients. This webinar will explore the spatial characterization of oral gut-selective versus systemically available JAK inhibitors in the mouse oxazolone model of ulcerative colitis using the GeoMx™ Digital Spatial Profiler (DSP) from NanoString®.

Preclinical in vivo characterization of localized drug inhibition can be challenging. Traditional analysis of gut-selective JAK inhibitors, utilizing whole tissue homogenization, is not able to resolve cell type-specific inhibition. GeoMx allowed for custom, multiplexed, and highly quantitative spatial sampling of mouse colons. Importantly, the platform’s single-cell masking capabilities mean that infiltrating immune cells in the intestinal mucosa can be sampled independently of non-immune tissue. This enabled the characterization of the spatial heterogeneity of the preclinical mouse model and to discriminate the effects of treatments on distinct cell types. Characterizing models up front can shorten time spent on model development, identify complex effects of target inhibition, and better characterize cell types involved with disease progression. By measuring inhibition in multiple cell types in spatially distinct layers of a mouse colon, the featured speaker will show that an oral gut-selective JAK inhibitor has similar inhibition compared to a systemic drug, but with markedly lower systemic exposure.

FOR RESEARCH USE ONLY. Not for use in diagnostic procedures.

Speaker

Whitney Krey-Epstein, Scientist, in vitro Pharmacology, Theravance Biopharma US, Inc

Whitney Krey-Epstein is a cell and molecular biologist at Theravance Biopharma US, Inc. During her ten years in the pharmaceutical industry, she has characterized three drugs that are currently in clinical trials and has supported a robust pre-clinical pipeline. At Theravance Biopharma, her focus is on demonstrating target engagement in cell-based and in vivo models. Her work primarily characterizes how small molecules treat a variety of immune-mediated diseases, including Inflammatory Bowel Disease. She completed her undergraduate work at Texas A&M University and her graduate work at the Massachusetts Institute of Technology.

Message Presenter

Who Should Attend?

  • Scientists utilizing mouse models (both academic and industry)
  • Pharmaceutical scientists working on projects with complex target distributions or unique drug distribution patterns
  • Pharmacologists
  • Immunologists
  • Cell and molecular biologists

What You Will Learn

  • The GeoMx Digital Spatial Profiler is a powerful way to characterize preclinical mouse inflammatory models
  • Highly multiplexed panels allow for deep measurement of inhibitor effects or model progression
  • Custom, single-cell masking capabilities allow for cell type-specific sampling
  • The platform revealed that an oral gut-selective JAK inhibitor has a similar inhibitory pattern to a systemic drug in the colon, but with markedly lower systemic exposure

 

 

Xtalks Partner

NanoString

NanoString Technologies (NASDAQ: NSTG) is a publicly held provider of life science tools for translational research and molecular diagnostics. The company’s technology enables a wide variety of basic research, translational medicine and in vitro diagnostics applications.

NanoString’s products are based on a novel digital molecular barcoding technology invented at the Institute for Systems Biology (ISB) in Seattle under direction of Dr. Leroy Hood. The company was founded in 2003 with an exclusive license to develop and market the technology. In 2008, NanoString launched its first commercial instrument system and began international sales operations with its first multiplexed assays for gene expression analysis. In 2010, the company launched new applications for the system to support microRNA analysis and copy number variation detection, and in 2013 launched Prosigna®, its first in vitro diagnostic product for prognosis of early stage breast cancer.

Organizations performing cancer research, biomarker validation and screening, and next-generation sequencing validation are rapidly adopting the nCounter® Analysis System. By providing simple, multiplexed digital profiling of single molecules, the NanoString platform represents a natural, digital downstream companion to next-generation sequencing and enables researchers to embark on studies that were previously inconceivable.

Leading researchers and institutions are finding that NanoString’s nCounter system provides the ideal platform on which to validate their discoveries and translate them into clinically useful diagnostic assays. The nCounter system is uniquely positioned to support translational research because it provides more reproducible results than methods requiring amplification, and generates high-quality data from the difficult sample types common in clinical research, including Formalin-Fixed Paraffin-Embedded (FFPE) tissues.

In addition to continuing to extend the applications for the nCounter system in the discovery, target validation and routine testing segments of the genomics research market, the company’s goal is to become the platform of choice for diagnostic testing based on multiplexed gene signatures that can be offered in hospitals and pathology laboratories worldwide, following appropriate regulatory approvals. These two synergistic areas of business focus provide researchers with a seamless transition from discovery to diagnostics.

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