Mo R. Ebrahimkhani, MD

Organoids, Synthetic Morphogenesis, Genetic Engineering, Regeneration and Repair, Liver, Hematopoietic system

Research Description

Laboratory for Synthetic Biology and Regenerative Medicine led by Dr. Ebrahimkhani combines synthetic biology, systems biology and stem cell engineering to advance regenerative medicine. The ability to engineer how cells sense, process, and respond to their environment via genetic engineering opens a new path to study biological systems and can be leveraged for the development of novel regenerative technologies. The research studies are summarized in Ebrahimkhani Lab Website.

1. Genetically Engineered Designer Organoids using human iPSCs: A single stem cell can produce the whole organism through genetically encoded molecular networks hardwired in DNA that results in coordinated multicellular behavior. Inspired by this capacity for organ development and regeneration, the lab employs genetic circuits to direct development of complex multicellular tissues (e.g. liver) from single human induced pluripotent stem cells (synthetic developmental engineering). The team has programmed stem cells towards self-vascularized human fetal and adult liver organoids with distinct cell types mimicking both native epithelial and mesenchymal cells. Current ongoing projects are:
   1. Development of mature human liver organoids from iPSCs through engineering genetic cascades, using synthetic biology, and computational analysis.
   2. Using [Designer Liver Organoids (DesLOs)] for regenerative therapy and for modeling human liver disease in personalized fashion.
   3. Engineering synthetic fetal liver niches and designer organoids to promote hematopoiesis and blood formation in vitro.
2. Early Developmental Engineering: Inspired by understanding gained from synthetic developmental engineering (A, above) the lab has recently used transcription factors to model early stages of embryo development in vitro to study early cell fate determination.
3. in vivo Epigenetic/Transcriptional Therapeutics: Dr. Ebrahimkhani has previously investigated liver regeneration and fibrosis using various mouse models. Inspired by those findings the lab uses advanced CRISPR-based genetic and epigenetic tools to program in vivo tissue homeostasis, immune response, and repair (collaboration with Kiani lab).
4. Liver-on-a-Chip for Human Translation of CRISPR: Dr. Ebrahimkhani's lab acts as a main collaborator in a recently funded NIH project that aims to develop a novel liver-on-a-chip platform for testing genetic engineering tools. The effort is part of the NIH Somatic Genome program that aims to facilitate safe translation of CRISPR tools for human applications. [https://commonfund.nih.gov/editing (collaboration with Kiani lab)].
5. Complex Multicellular Behavior, Emergence and Ecology. The lab has an ongoing interest in elucidating intercellular interaction networks in complex multicellular entities through application of principles of complex systems, ecology and control theory.