Engineering the stromal secretome to program organ development and maturation

Organoids, lab-grown mini-organs grown from human stem cells, hold the promise to yield new information about our own organs in health and disease. But these engineered mini-organs are nowhere near an exact replica of the real thing — they are far simpler and biologically “younger.” This may be in part because they are missing certain kinds of cells and tissues present in the body. Pulin Li, Ph.D., is leading a project to introduce a type of tissue known as the stroma into organoids. The stroma acts as a sort of living cushion or scaffolding for other kinds of cells, providing physical support as well as molecular signals that guide organ development. It’s also involved in wound repair, inflammation and cell renewal. Li’s hope is that organoids that include stromal cells will provide better models of actual human organs, allowing researchers to better understand our own health and development and providing a platform for rapid preclinical drug testing.  

Affiliated Investigators

Pulin Li, Ph.D.

Massachusetts Institute of Technology

Dr. Pulin Li is a member of the Whitehead Institute and the Eugene Bell Career Development Professor in the Department of Biology at Massachusetts Institute of Technology. She completed a Ph.D. in Chemical Biology with Dr. Leonard Zon from Harvard University, where she discovered novel signaling pathways that regulate hematopoietic stem cells during embryo development and adult stem cell transplantation. She then completed postdoctoral work with Dr. Michael Elowitz at California Institute of Technology, studying how cell-cell communication coordinates tissue patterning. To answer this central question in developmental biology, she developed a bottom-up approach by genetically engineering communication circuits in individual cells and then reconstituting multicellular interactions in a petri dish, which led to the successful reconstitution of morphogen gradients, a key module in embryo development. Using this approach, together with quantitative imaging and mathematical modeling, she discovered crucial roles of negative feedback loops in ensuring the precision of morphogen gradients and tissue patterning. At Whitehead Institute, her lab is further developing molecular, cellular and computational tools to expand our capability of engineering genetic circuits and reconstituting multicellular interactions. The lab is applying these tools to study a broad range of tissue-level questions, with a keen focus on understanding how the spatial relationship among diverse cell types is established and how the spatial organization influences tissue physiology. These engineering efforts are also complemented with quantitative analysis in natural tissues. Dr. Li is a recipient of the NIH Pathway to Independence award, NIH Director’s New Innovator Award, Santa Cruz Developmental Biology Young Investigator Award, and R. R. Bensley Award from the American Association of Anatomy.