Gadue Laboratory



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The use of human models systems to study human biology and disease is critical as animal models, while being an invaluable resource, can sometimes fail to recapitulate human physiology and disease due to species differences in biology. Therefore, the Gadue laboratory uses human embryonic stem (ES) cell and induced pluripotent stem (iPS) cell model systems. ES/iPS cells can be expanded in vitro while maintaining the ability to differentiate into all cell types in the body. We are using this system to model disease processes and developmental pathways with the goal of developing new therapies for human diseases.

The differentiation of ES cells into a given cell type closely mimics how that cell is formed during embryogenesis. This developmental process starts with the formation of the primary germ layers, mesoderm, endoderm, and ectoderm with progressively more differentiated cell type forming until a functional mature cell is generated. The lab's research program focuses on understanding the molecular mechanisms that regulate endoderm and mesoderm development.

One area of interest in the lab is in investigating hematopoiesis with a focus on megakaryocyte development, with the goal of optimizing the generation of platelets in vitro from ES/iPS cells. In addition, the lab is developing models of platelet disorders using iPS cells derived from patients with genetic diseases affecting platelet development and function as well as using CRISPR/Cas9 technology to both correct mutant iPS cell lines and generate patient specific mutations in wild-type lines.

The second area of interest in the lab is endoderm development, using the human stem cell model to study pancreas, liver, and lung specification. We are also investigating pancreatic beta cell development with the goal of generating functional beta cells from human ES and iPS cells. Lastly, we are using the stem cell system to model genetic predisposition to diabetes, using both patient-specific iPS cells and genome editing to generate genetic models of these diseases.

Project Highlights

  • Optimization of megakaryocyte and platelet generation from pluripotent stem cells.
  • Modeling genetic bleeding disorders with human pluripotent stem cells.
  • Studying human endoderm patterning and pancreas development.
  • Modeling diabetes both monogenic as well as type 2 diabetes with human pluripotent stem cells.
Paul Gadue

Paul Gadue, PhD

Associate Director, Human Embryonic Stem Cell Core
Dr. Gadue studies cell fate decisions, focusing on endoderm and mesoderm specification using human embryonic stem (ES) cells and induced pluripotent stem (iPS).