2018 Exploratory Grantees

Investigators: David Antonetti, Ann Miller, Anuska Andjelkovic-Zochowska, Asma Nusrat

Multicellular organisms require maintenance of defined environments provided by tissue barriers for proper function. Nearly every organ system in the human body requires some degree of barrier formation – whether it is in epithelial sheets coating organs or lining ducts, or in endothelial tubes of vessels. These barriers are often disrupted in disease conditions. However, developing methods to safely and specifically deliver therapeutics across these barriers remains a major challenge, particularly for diseases of the nervous system. The Biosciences Initiative Funding Opportunity provides an opportunity to build upon the University of Michigan’s current strength in Barriers Biology by further developing our expertise and encouraging new collaborations among barriers researchers. The focus of The Role of Tissue Barriers in Health and Disease is to recruit outside experts to work alongside U-M experts to facilitate two multi-day workshops on emerging areas for the Michigan Barriers Biology community.

Learn more from the executive summary.

Investigators: Christopher Friese, Jeff DeGraff, Sarah Hawley, Kenneth Resnicow

Faculty members affiliated with The Center for Improving Patient and Population Health (CIPPH) have demonstrated expertise in improving the health and well-being of at-risk populations. Examples include improving the treatment experience for patients with cancer, applying simulation science to enhance clinical preparedness, and using novel web-based interventions to reduce environmental hazards. The Applying an Innovation Framework to Improve Health in Rural Populations project vision is to bring this diverse expertise together in novel ways to transform the well-being of individuals who are historically underserved, with an emphasis on rural residents. To advance this vision, a state-of-the-science workshop will develop to identify the most pressing gaps in rural health conducive to Michigan faculty expertise, apply an innovation framework to forge partnerships with experts and key stakeholders, and secure robust, sustainable funding.

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Investigators: Sundeep Kalantry, Uhn-soo Cho, Yali Dou, Shigeki Iwase, Kaushik Ragunathan

Single cell transcriptional profiling has revealed considerable heterogeneity of gene expression even within genetically identical populations of cells. These differences are postulated to contribute to cell fate decisions both during normal development and in diseases. However, the source of this transcriptional heterogeneity is unclear. Changes in the chromatin state of defined loci are prime candidates to underlie transcriptional heterogeneity between cells with an apparently identical developmental potential. However, single-cell chromatin profiling and single-locus chromatin proteomics remain a significant hurdle in the field of chromatin biology, especially at increasingly low-input and higher resolution levels. With support from the Biosciences Initiative, we will develop, import, and distribute to the University of Michigan research community reagents and technologies that will enable single-cell and locus-specific chromatin proteomics. This capability will help illumine fundamental mechanisms underlying cell- and locus-specific transcriptional heterogeneities both during normal development and in disease.

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Investigator: Jonathan Sexton

The traditional drug development process has a timeline of 11–18 years and costs approximately $1–3 billion dollars to bring a novel drug to market. This timeline results in a decades-long delay between advances in basic biomedical science and effective therapies for unmet medical needs. Discovering new uses for existing drugs can offer the shortest path from initial discovery to clinical use as well as reduce the cost of development and reduce risk in commercialization. The U-M Re-Targeting Discovery Platform will create a drug repurposing platform consisting of a comprehensive collection of clinically-evaluated small molecules and an associated informatics resource to enhance drug discovery and translational medicine research at the University of Michigan. This clinically-evaluated compound collection will stimulate innovation and help address unmet medical needs by connecting the wealth of biological models in the U-M research community with highly translatable and actionable hits from in vitro screening.

Learn more from the executive summary.