Much of what we know about mammalian biology we have learned from the mouse. However, improvements to human health will ultimately require a better understanding of the integrative biology of human, rather than mouse, tissues. Our understanding of human biology is limited because no experimentally tractable system is available to study human cells in the context of the complex cellular interactions that are characteristic of tissues in vivo. This proposal addresses this unmet need by proposing the synthesis of the most structurally complex and detailed model of a human tissue to date. We will take a combined top-down and bottom-up approach toward this goal, using modular chemical tools to control the spatial organization of multiple cell types in a 3D tissue. We will focus on te mammary gland as the target organ due to its unique developmental biology, relevance to human disease, and important structural differences when compared to model mammalian organisms (Parmar and Cunha, 2004). Our efforts will also be facilitated by a plethora of commonly available and renewable cell sources derived from human tissues that are unique to the mammary gland. Completion of our efforts will provide a revolutionary in vitro model for studying the biology of human tissues and for testing therapeutics. In addition, our fundamentally synthetic approach will force us to challenge commonly held assumptions about the organization and function of human tissues, and will thereby reveal new and exciting biology in the process. The modular synthetic strategies perfected in the course of this proposal will be applicable to many other human tissues, maximizing the impact of this work to the broader biomedical community.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
NIH Director’s New Innovator Awards (DP2)
Project #
1DP2HD080351-01
Application #
8572995
Study Section
Special Emphasis Panel (ZRG1-MOSS-C (56))
Program Officer
Raiten, Daniel J
Project Start
2013-09-30
Project End
2018-07-31
Budget Start
2013-09-30
Budget End
2018-07-31
Support Year
1
Fiscal Year
2013
Total Cost
$2,372,625
Indirect Cost
$872,625
Name
University of California San Francisco
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Cerchiari, Alec E; Samy, Karen E; Todhunter, Michael E et al. (2016) Probing the luminal microenvironment of reconstituted epithelial microtissues. Sci Rep 6:33148
Seo, Daeha; Southard, Kaden M; Kim, Ji-Wook et al. (2016) A Mechanogenetic Toolkit for Interrogating Cell Signaling in Space and Time. Cell 165:1507-18
Cole, Russell H; Gartner, Zev J; Abate, Adam R (2016) Multicolor Fluorescence Detection for Droplet Microfluidics Using Optical Fibers. J Vis Exp :
Todhunter, Michael E; Weber, Robert J; Farlow, Justin et al. (2016) Fabrication of 3-D Reconstituted Organoid Arrays by DNA-Programmed Assembly of Cells (DPAC). Curr Protoc Chem Biol 8:147-78
Coyle, Maxwell; Hu, Jennifer; Gartner, Zev (2016) Mysteries in a Minimal Genome. ACS Cent Sci 2:274-7
Ouyang, Ann; Cerchiari, Alec E; Tang, Xinyan et al. (2016) Effects of cell type and configuration on anabolic and catabolic activity in 3D co-culture of mesenchymal stem cells and nucleus pulposus cells. J Orthop Res :
Chen, Sisi; Bremer, Andrew W; Scheideler, Olivia J et al. (2016) Interrogating cellular fate decisions with high-throughput arrays of multiplexed cellular communities. Nat Commun 7:10309
Broaders, Kyle E; Cerchiari, Alec E; Gartner, Zev J (2015) Coupling between apical tension and basal adhesion allow epithelia to collectively sense and respond to substrate topography over long distances. Integr Biol (Camb) 7:1611-21
Cerchiari, Alec; Garbe, James C; Todhunter, Michael E et al. (2015) Formation of spatially and geometrically controlled three-dimensional tissues in soft gels by sacrificial micromolding. Tissue Eng Part C Methods 21:541-7
Cole, Russell H; de Lange, Niek; Gartner, Zev J et al. (2015) Compact and modular multicolour fluorescence detector for droplet microfluidics. Lab Chip 15:2754-8

Showing the most recent 10 out of 14 publications