Home              Research              People              Publications              Software              Computers              Positions              Contact

Our research goals are to identify genetic determinants and environmental risks underlying selected human diseases (including developing new analytic approaches), and determine how these risks contribute to disease etiology, with the ultimate goal to inform diagnosis, treatment, disease risk prediction, early intervention, and prevention. We plan to develop three directions: bioinformatics development, disease risk discovery, and translational genomics. Below are representative projects for each category.

Bioinformatics development

 a.    Develop new platform to genotype ERVs using long reads sequencing: We will use Pacific Biosciences and/or Nanopore long read sequencing to improve my current algorithm for ERV detection (ERVcaller version 1 was published in Bioinformatics). Our new platform (ERVcaller version 2) will identify ERV and other transposable element variants that are not detectable by Illumina short reads.

 b.    Develop new platform to detect mosaic viral integrations for brain disorders: We will improve our current algorithm for viral integration detection (VIcaller ver. 1 was published in Genome Research). Our new platform (VIcaller ver. 2) aims to detect mosaic viral integration events in blood and/or brain samples using ultra-deep sequencing and/or long reads, allowing for testing hypotheses whether viral infections are involved in some brain behavioral disorder cases on the human virome level. This platform can also be extended to the human bacteriome level.

Disease risk discovery

a.     Identify ERV variations and ERV expression in alcohol use disorder (AUD): We recently collected WGS data from AUD samples as well as RNA-Seq data from AUD brain PFC, ethanol treated human embryonic stem cell-derived neurons, and alcohol use mouse brains. Our pilot analyses showed that ethanol induced ERV activation and expression in neurons; AUD brains exhibited elevated ERVs expression than controls; and ERV genotypes were associated with AUD. Thus, we will conduct comprehensive analyses of the data. ERVs Identified from this study may explain both familial inheritance and immune response/inflammation observed in AUD. We am also interested to examine developmental and environmental modulators, such as stress; childhood maltreatment; nutrients, which may be potential ERV activators. This ERV analysis can be applied to other brain disorders (for example, GWAS by the psychiatric genomics consortium support a link between the immune system and schizophrenia).

b.     Identify genomic/epigenomic/ERV risks in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): We are generating omics data (genome, transcriptome, epigenome, microbiome, and brain images) from patients with ME/CFS. We have prepared in-house pipelines, and will use them to identify risk factors, particularly ERVs, that may explain the altered immune responses and neuroinflammation observed in ME/CFS.

Translational medicine

a.     Identify AUD early stage risks: AUD is a progressive, lifetime disease. Once an individual develops AUD, it is hard to cure. However, AUD is preventable. The best period for prevention is late childhood and adolescence. Elucidating the developmental pathways from early onset symptoms to AUD and identifying pediatric behavioral, brain, and genetic markers will help at-risk children for early intervention. This study aims to use a lifespan approach to identify developmental pathways to AUD using phenome-genome data of over 12000 individuals who have struggled with AUD. This study will generate actionable data that may be used to design intervention and preventative strategies for AUD and related deaths.

 b.     Potential treatment in neuroinflammatory diseases: There are anti-retroviral clinical trials to suppress ERV expression in multiple sclerosis and amyotrophic lateral sclerosis. ME/CFS share symptoms with multiple sclerosis (e.g., chronic fatigue and pain). If our analyses prove that ERVs are risk in ME/CFS and/or addiction, the existing FDA-approved anti-retroviral or anti-inflammatory drugs can be repurposed to reverse ERV effects. Interestingly, in clinical practice, the medications used for ME/CFS patients include medications designed for addiction treatment (such as Naltrexone), indicating the two diseases share some biology in common.