The research plan of my team integrates the fields of synthetic biology, genetic manipulation, genome engineering, and human disease modeling, into the building of novel, increasingly more powerful synthetic genetic technologies tailored to tease apart, understand and treat complex biomedical phenotypes using eukaryotic cells and animals as model systems. The technologies are designed to reproducibly recapitulate complex phenotype formation and disease pathogenesis, that are then further in-depth qualitatively probed for underlying genetic interactions, cellular dysfunction, aberrant systems physiology, as well as genetic, preventive or pharmaceutical intervention.
Read More
The research plan of my team integrates the fields of synthetic biology, genetic manipulation, genome engineering, and human disease modeling, into the building of novel, increasingly more powerful synthetic genetic technologies tailored to tease apart, understand and treat complex biomedical phenotypes using eukaryotic cells and animals as model systems. The technologies are designed to reproducibly recapitulate complex phenotype formation and disease pathogenesis, that are then further in-depth qualitatively probed for underlying genetic interactions, cellular dysfunction, aberrant systems physiology, as well as genetic, preventive or pharmaceutical intervention.
To fulfill this research plan, my lab develops novel: 1) Synthetic genetic transgenesis and genome engineering technologies to model complex phenotypes: Engineer defined synthetic genetic circuits to generate more efficient cellular and animal models by site-specific genome manipulations to study complex phenotype formation or pathogenesis. 2) Synthetic forward-genetics technologies to identify novel genes and pathways involved in complex phenotypes: Engineer and mobilize concatameric arrays of synthetic genetically encoded mutagens (e.g., typical cut-and-paste transposons and others) in model systems using comprehensive pools of sensitized genetic backgrounds relevant to complex phenotypes or human disease, resulting in in-depth saturated forward genetic genome interrogation and the identification of novel unique events that are critical during complex phenotype formation or pathogenesis. 3) Synthetic reverse- (combinatorial) genetics technologies to probe and analyze complex phenotypes: Synthetically assemble sophisticated (combinatorial) genetics tools to dissect at once large groups of candidate genes and pathways, previously isolated by transposon hopping or other means, for their individual and collateral roles during complex phenotype formation or pathogenesis. 4) Synthetic diagnostic and drug discovery genetic technologies to investigate pathway interactions, malfunctioning, and intervention in complex phenotypes: Engineer synthetic multi-reporter arrays, founded on orthogonal luciferases, fluorescent proteins, or other genetically encoded reporters, to concomitantly examine multiple signaling pathways that are participating in complex phenotypes and human diseases. 5) Synthetic therapeutic genetic technologies to precisely manipulate and treat complex phenotypes: Founded on the orthogonal spatiotemporal regulations of a variety of genetic tools or cellular pathways, stitch together genetic circuits for on-demand multi-manipulations of complex phenotypes in model systems or treatment of multigenic human diseases.
Read Less
