Julia Li

Half of our genome consists of repeat sequences that resemble viral DNA, yet the functional significance of these virus-like repeats remains a mystery. Abnormal repeat sequences have been found at unstable genomic regions implicated in cancer and genetic diseases. However, how repeat sequences threaten the stability of our genome is not well understood. Finally, DNA viruses detected in cancer cells are also prime suspects in promoting genomic instability. For decades, these unsolved, seemingly connected observations pointed towards a missing mechanism.

By observing two fluorescent nuclear signals of the Epstein Barr Virus Nuclear Antigen 1 (EBNA1), we found this missing piece to the puzzle: a cluster of Epstein Bar Virus (EBV)-like repeat sequences in our genome that can break and trigger chromosomal abnormalities in cells infected with EBV.  The overall goal of our lab is to leverage this initial discovery to identify the missing link between repeat DNA, genomic instability, and viruses. Specifically, we employ advanced techniques in molecular biology, cell biology, single cell analysis, genome-wide sequencing, unbiased proteomics, and functional genomics to answer the following questions:

1. How do virus-like DNA repeat sequences break?

2. How does virus-induced chromosomal breakage fuel genomic chaos in cancer and genetic diseases?

3. What pathological conditions trigger breakage in viral infection?

4. What is the role of virus-like DNA repeat sequences in normal genome structure and function?

In the long run, we are excited about potentially uncovering a class of viral proteins that play a role in human health and disease by binding to virus-like repeat sequences in our genome.  Ultimately, understanding basic mechanisms surrounding virus-like repeat sequences will create new opportunities for the prevention and treatment of viral infection-associated cancer and genetic diseases.