Yinqing Li, a researcher from the School of
Pharmaceutical Sciences at Tsinghua University, has been fascinated by the human brain
since childhood.
New tools are urgently needed to understand
and develop better cures for complex human diseases, especially severe mental
illness, which has been largely lacking any meaningful treatment. During
his time at the Massachusetts Institute of Technology (MIT), Li developed
methodologies and computational pipelines that enable comprehensive profiling
of single neurons from the brain and the spinal cord. This new technique made
it possible to analyze spinal nerve regeneration, a process even rarer in a
healthy adult; the understanding of which is critical for developing cures for
spinal injuries. He co-authored a paper based on these findings in the journal, Science, in 2016. This technology has attracted attention because of its potential in drug development and clinical testing.
Conventional single cell genomics has
limited applications in the detailed study of neuronal cells due to the difficulties
in the isolation of single neurons. His approach was to profile single nuclei
instead of neurons. He created an analysis framework to identify cell types
using the nucleus RNA based on statistical modeling and enrichment of cell type
signatures. The single nucleus technology not only enables characterization of
known and novel nerve cell types, including long-sought newborn neurons in the
intact spinal cord, but also makes it possible to analyze clinical samples with
high fidelity. Moreover, he co-founded Rootpath Genomics to fully realize the
potential of single nucleus technologies in industrial and clinical applications.
Li took another step forward and constructed
a single cell characterization framework (or a neural single-cell multi-omics
technique) that integrates anatomy, connectivity, neuronal activities, and underlying molecular regulation at the single cell resolution level.
This technique reveals that the inhibitory
neurons in a certain brain region — the
periphery of the thalamus — are a key component
to the core neural circuits associated with mental disorders, such as hereditary
ADHD, providing important clues for screening potential drug targets.
Besides single neurons genomics, Li also made
contributions to the development of CRISPR-Cas9 gene editing technology,
including a computational model for deriving factors that are important for gene
editing specificity, accounting for positions and base identities of mismatches.
His co-authored patent, based upon this model, has led to widely used target
screening algorithms.
In all, he developed a number of genomics
technologies and methodologies integrating diverse fields, including machine
learning, bioinformatics, systems biology, genomics, and molecular and cellular
engineering. These technologies will have broader applications in other systems
and will provide the foundation for disease relevant discoveries.
