Only less than 2% of the human genome encodes proteins. The rest non-coding part has long been called ‘junk’ DNA. However, we found that some of the non-coding regions are highly conserved among species and many of them act as cis-regulatory elements controlling the expression of target genes in diseases and development. Moreover, recent genome-wide association studies (GWAS) have revealed that more than 90% of disease risk variants are located in the non-coding regions. So, the non-coding regions are not “junk”, but rather the “dark matter” in the universe of the human genome. Our research interest is to discover the regulatory elements in the non-coding regions of the human genome and their functions in health and complex neurological diseases, such as Parkinson's disease and Alzheimer’s disease.

Through developing novel computational methods to analyze the transcriptome of the human brain neurons, we have discovered over 71,000 transcribed non-coding elements in dopamine neurons, at least one third of which are active enhancer RNAs (eRNAs) with in vitro and in vivo evidence (Dong et al. Nature Neuroscience, 2018). We continue to explore the hidden landscape of other non-coding RNAs, incl. circRNAs, piRNAs in human brains and their functions in neurodegenerative diseases. 

We are also interested in applying advanced machine learning methods to integrate individual’s omics, clinical, imaging, and activity data to predict disease diagnosis, prognosis, and progression. Additionally, we are running the Genomics and Bioinformatics Hub (https://bioinformatics.bwh.harvard.edu/) at Brigham and Women’s Hospital, providing collaborative service and training in genomics and bioinformatics to all labs in the neuro community in Brigham and Women’s Hospital and Harvard Medical School.