Background and Research areas
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We study principles of morphogenesis and develop technologies to modulate those processes.Our research combines systems and synthetic biology-based approaches to elucidate cellular interaction networks during tissue development and regeneration. We examine how cellular ecology within multiple cell populations controls the fate of complex tissue. Our research is informed by findings from studies in mouse models and applies synthetic biology approaches to engineer better in vitro human tissue surrogates. Through genetic engineering of self-organization in human stem cells, we have developed novel organoids. We are studying the dynamics of morphogenesis using our developed self-vascularized fetal liver tissues. Our vision is to advance regenerative medicine through integrating systems and synthetic biology.
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: https://www.nytimes.com/2017/06/12/health/liver-bodily-function.html (image from Guyco, nytimes.com ) |
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Organoids, Human Tissues by Design, Stem Cell Engineering
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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.
Selected references: 1. Synthetic Maturation of Multilineage Human Liver Organoids via Genetically Guided Engineering. bioRxiv. 2020 May 10. 2. Programming Morphogenesis through Systems and Synthetic Biology. Trends in Biotechnology. 2018 Apr;36(4):415-429. 3. Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6. Nat Commun. 2016 Jan 6;7:10243. 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. |
Tissue Dynamics, Synthetic Developmental Biology
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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. Selected references: 1. Synthetic Maturation of Multilineage Human Liver Organoids via Genetically Guided Engineering. bioRxiv. 2020 May 10. 2. Synthetic developmental biology: build and control multicellular systems. Current opinion in chemical biology. 2019 Oct 1;52:9-15. 3. Programming Morphogenesis through Systems and Synthetic Biology. Trends in Biotechnology. 2018 Apr;36(4):415-429. 4. Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6. Nat Commun. 2016 Jan 6;7:10243. |
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Regenerative Technologies (focus: Genetic Engineering)
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In collaboration with Dr. Kiani's lab at Pitt 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.
Selected References: 1. CRISPR-Based Synthetic Transcription Factors In Vivo: The Future of Therapeutic Cellular Programming. Cell Systems. 2020 Jan 22;10(1):1-4. 2. Multifunctional CRISPR-Cas9 with engineered immunosilenced human T cell epitopes. Nature communications. 2019 Apr 23;10(1):1-0 3. Cas9 gRNA engineering for genome editing, activation and repression. Nat Methods. 2015 Nov;12(11):1051-4. 4.CRISPR transcriptional repression devices and layered circuits in mammalian cells. Nat Methods. 2014 Jul;11(7):723-6. 5. 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 |
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