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Li Lab Research
PCMM Research

Research Overview

DNA repeat sequences in our genome resemble viral DNA, yet the functional significance of these virus-like repeats remains a mystery. Abnormal repeats have also been found at unstable genomic regions implicated in cancer and genetic diseases. Again, how these repeats contribute to genomic instability is poorly understood. Finally, while DNA viruses like Epstein Barr Virus (EBV) have been associated with cancer, it is not clear how exactly these viruses contribute to the development of cancer. For decades, these seemingly disparate yet connected observations pointed towards a missing link between repeat DNA, genomic instability, and viruses.

Dr. Li’s recent discovery of a cluster of EBV-like repeats in our genome provides this missing piece to the puzzle. She showed how virus-like DNA repeats can break and trigger chromosomal abnormalities when bound by a viral protein produced in latent infection. Based on this discovery, the Li lab will uncover the missing mechanistic link fundamental to the relationship between humans and viruses in health and disease. Currently, the lab is excited about investigating:

  1. How virus-like DNA repeat sequences undergo breakage
  2. How such breakage shapes abnormal genomes that underlie cancer and genetic diseases
  3. Pathological conditions in viral infection that trigger breakage
  4. Functional significance of these DNA repeat sequences in viral infection

Ultimately, the Li lab is excited about potentially uncovering a fundamental link between humans and viruses that plays a role in human health and disease. Understanding these basic mechanisms surrounding virus-like repeats will create new opportunities for the prevention and treatment of viral infection-associated cancer and genetic diseases.

Research Background

Julia Li received her Ph.D. in Molecular Biology from the Scripps Research Institute (La Jolla, CA) under the direction of Dr. Eros Lazzerini Denchi in 2018; subsequently she trained as a postdoc with Dr. Don Cleveland in the Department of Cellular and Molecular Medicine, University of California at San Diego (San Diego, CA). In 2024, she was appointed an Investigator and Assistant Professor in the Program in Cellular and Molecular Medicine at Boston Children's Hospital, and in the Department of Genetics at Harvard Medical School, respectively.

 

Selected Publications

  1. Chromosomal fragile site breakage by EBV-encoded EBNA1 at clustered repeats. Nature. 2023 Apr; 616(7957):504-509.
  2. TZAP overexpression induces telomere dysfunction and ALT-like activity in ATRX/DAXX-deficient cells. iScience. 2023 Mar 14;26(4):106405.
  3. Chromothripsis drives the evolution of gene amplification in cancer. Nature. 2021 Mar;591(7848):137-141.
  4. Telomere length heterogeneity in ALT cells is maintained by PML-dependent localization of the BTR complex to telomeres. Genes Dev. 2020 May 1;34(9-10):650-662.
  5. How stem cells keep telomeres in check. Differentiation. 2018; Mar-Apr:100:21-25.
  6. TZAP: A telomere-associated protein involved in telomere length control. Science. 2017; Feb 10;355(6325):638-641.
  7. Seamless Insert-Plasmid Assembly at High Efficiency and Low Cost. PLoS One. 2016 Apr 13;11(4):e0153158.
  8. Limited genomic heterogeneity of circulating melanoma cells in advanced stage patients. Phys Biol. 2015; Jan 9;12(1):016008.
  9. Let it go: how to deal with a breakup in mitosis. Nat Struct Mol Biol. 2014 May;21(5):433-5.
  10. Isolation of chromatin from dysfunctional telomeres reveals an important role for Ring1b in NHEJ-mediated chromosome fusions. Cell Reports. 2014 May 22;7(4):1320-32..

Contact Julia Li

Phone: 617-919-1928
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