I am the John T. Wilson Distinguished Service Professor in the Department of Chemistry and Department of Biochemistry and Molecular Biology at the University of Chicago. I received my Bachelor of Science degree in 1994 from the University of Science and Technology of China and my PhD in chemistry from the Massachusetts Institute of Technology in 2000, studying under professor Stephen J. Lippard. After training as a Damon-Runyon postdoctoral fellow with professor Gregory L. Verdine at Harvard University, I joined the University of Chicago as an assistant professor in 2002, rising to associate professor in 2008 and full professor in 2010. I served as the director of the Institute for Biophysical Dynamics at the University of Chicago from 2012-2017 and was selected as an investigator of the Howard Hughes Medical Institute in 2013.

Our recent research has been focusing on understanding how chemical modifications on RNA regulate gene expression, and to translating that chemistry into new tools for cancer diagnosis and therapy. My lab’s 2011 discovery of FTO as the first RNA demethylase established that N6-methyladenosine (m6A) as a reversible and dynamically regulated mark, the founding observation of the field now known as epitranscriptomics. We went on to identify and characterize the YTH-domain “reader” proteins that recognize m6A to control mRNA stability and translation, and more recently showed that RNA methylation on chromatin-associated RNA shape chromatin state directly, with nuclear readers such as YTHDC1 and RBFOX2 interpreting these marks to recruit histone-modifying complexes.

Much of my current work traces these RNA chemical marks into cancer biology. My lab discovered a chromatin-regulatory pathway in leukemia driven not by DNA or histone marks but by 5-methylcytosine (m5C) on chromatin-associated RNAs, and found that TET2, a tumor suppressor long thought to act mainly through DNA oxidation, instead exerts much of its anti-leukemic effect by oxidizing m5C on RNA. We have also shown that a hot-spot mutation in the m6A methyltransferase complex drives endometrial cancer, and that m6A reader proteins such as YTHDF1 and YTHDF2 suppress anti-tumor immunity by limiting dendritic cell antigen presentation and promoting immunosuppressive myeloid cells in the tumor microenvironment. We are now developing small-molecule inhibitors of these reader proteins as a new class of cancer immunotherapy.

Most recently, my group developed a liquid biopsy that detects RNA modifications, rather than DNA, in cell-free RNA from human and gut-microbial sources, achieving roughly 95% accuracy in identifying early-stage colorectal cancer, the first demonstration that RNA modifications can serve as blood-based cancer biomarkers.