He got involved in the NIH’s Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative consortium, and led the comprehensive analyses of gene regulatory programs in both human and mouse brains from >3 million single-cell epigenetic and multi-omics profiles. These comprehensive analyses characterized the first atlas of cis-regulatory DNA elements (cCREs) in the mammalian brain, and uncovered a significant degree of evolutionary changes involving both sequence turnovers and regulatory divergence, which can assist in interpreting noncoding risk variants that contribute to various neurological diseases in humans. Dr. Li further interrogated the regulatory codes and predicted the influence risk variants have on gene regulation using deep learning models. Besides, he has built a web portal called CATlas (cis-elements atlas, http://catlas.org) for exploring single-cell epigenetic datasets.
His work provides a framework for studying the combined effects of genetic and epigenomic mechanisms in a cell-type-specific manner, which can be applied to the studies of a wide range of brain functions and disorders.