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.