Our roads to uncertainty usually start from liver. In this article you can find why:
The Liver: A ‘Blob’ That Runs the Body
NEW YORK TIMES:
(image from Guyco, nytimes.com )
Organoids and Stem Cell Engineering
We use human induced pluripotent stem cells and through applying genetic engineering approaches direct their fates to Complex tissues such as human liver organoids. Our approach involves engineering self-organization of human stem cells to tissues and 3D organ-like structures . The technology we develop is a novel approach to produce tissue model systems and can fill the gap between mouse studies and human trials. Our studies have several applications such as understanding human organogenesis, human disease modeling, platform for drug testing and personalized disease therapeutics . In this section we are applying bioengineering tools to control emergence of biological structures and associated cellular fates.
1. Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6. Nat Commun. 2016 Jan 6;7:10243.
2. Approaches to in vitro tissue regeneration with application for human disease modeling and drug development. Drug Discov Today. 2014 Jun;19(6):754-62.
We investigate cell fate selection and dynamics within mammalian multicellular systems. The goal in this part of our studies is to underpin the design principle of tissue morphogenesis. In this line, we study how cell-cell communications drive final tissue structure and function (e.g. endothelial fate vs hepatocyte fate or healthy regeneration vs maladaptive fibrosis). Here, we apply systems analysis and imaging technologies to better understand the underlying cellular and molecular events in the liver tissue.
1. Programming Morphogenesis through Systems and Synthetic Biology. Trends in Biotechnology 2018 Apr;36(4):415-429.
2. Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6. Nat Commun. 2016 Jan 6;7:10243.
In collaboration with Dr. Kiani's lab at ASU we have contributed to the development of genetic tools that enable precise control over cell fate and function. Here, within a collaborative effort we apply these novel genetic toolsets to control final cell fate and the emergence of tissue behavior in several model systems of human diseases.
1.Cas9 gRNA engineering for genome editing, activation and repression. Nat Methods. 2015 Nov;12(11):1051-4.
2.CRISPR transcriptional repression devices and layered circuits in mammalian cells. Nat Methods. 2014 Jul;11(7):723-6.
3.Aag-initiated base excision repair promotes ischemia reperfusion injury in liver, brain, and kidney. Proc Natl Acad Sci U S A. 2014; 111:E4878-86
4.Approaches to in vitro tissue regeneration with application for human disease modeling and drug development. Drug Discov Today. 2014 Jun;19(6):754-62.