Merrill Meadow | Whitehead Institute
February 9, 2022
Whitehead Institute Member Pulin Li has been selected by The Paul G. Allen Frontiers Group to be an Allen Distinguished Investigator. The Allen Distinguished Investigator program backs creative, early-stage research projects in biology and medical research that would not otherwise be supported by traditional research funding programs. Each Allen Distinguished Investigator award provides three years of research funding.
Li, who is also an assistant professor of biology and the Eugene Bell Career Development Professor of Tissue Engineering at Massachusetts Institute of Technology, studies how circuits of genes within individual cells enable multicellular functions and phenomena such as the patterns of varied cell types that comprise a tissue. Her lab combines approaches from synthetic biology, developmental biology, biophysics, and systems biology to quantitatively understand how cells communicate to produce those phenomena. The work could lead to ways to program stem cells to form tissues for regenerative medicine.
“I am very grateful for this generous support ,” Li says. “The Frontiers Group’s commitment to early-stage investigations is welcome by scientists who are trying to open new paths to discovery.”
Li’s project seeks to advance the field of synthetic developmental biology through improving the process researchers use to create small groups of cells that develop certain functions of organs. Known as organoids, these tissues enable researchers to learn more about how organs develop and function in both healthy and diseased states; and they could be used for rapid and accurate preclinical drug testing.
“All organs in our body are ecosystems of different cell types that constantly talk to each other and regulate each other’s fates, and the challenge researchers face is creating organoids that reflect this multifaceted interaction,” Li explains. “Organoids that include a more complex and complete suite of tissues may prove to function more like real organs. In the project supported by the Allen Distinguished Investigator award, my lab seeks to improve the development of organoids by introducing a type of supportive tissue known as the stroma.”
Most organs are made of epithelial cells juxtaposed with the stroma’s connective tissue. Within the stroma, mesenchymal cells help to orchestrate tissue formation and the spatial organization of other cell types. The versatile function of mesenchymal cells critically depends on their extraordinary capability to produce an array of molecules that can stimulate other cell types.
As a result, each population of mesenchymal cells has distinct capability to support the development of other cell types, control organ shapes, respond to tissue injury, and regulate inflammation.
“Despite the important function of mesenchymal cells,” Li says, “they are mostly missing in the organoids that researchers have thus far developed. Our goal is to engineer diverse populations of human mesenchymal cells and reconstitute their spatial relationship and communication with other cell types in the stroma.
“Ultimately, we believe, these synthetically engineered stroma will help unleash the full potential of organoids as useful tools for studying organ formation and physiology.”
The Paul G. Allen Frontiers Group was founded in 2016 by the late philanthropist Paul G. Allen to explore the landscape of bioscience and to identify and foster ideas that will change the world. Its Allen Distinguished Investigators program advances frontier explorations with exceptional creativity and potential impact.