Our Research

The Li Lab is located in the Women’s Oncology Center in MR-6, and is associated with the Pathology Department of the University of Virginia Medical School.
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One of the central paradigms is that genes are located in isolated zones, minding their own business (making their own RNAs and proteins) and don’t usually cross talk with each other, except in pathological situations. For example, one of the hallmarks in cancer is DNA rearrangement, which results in the fusion of two separate genes. These gene fusion products often play critical roles in cancer development. Traditionally, they are thought to be the sole product of DNA rearrangement and therefore unique to cancer. This belief forms the basis for many cancer diagnostic and therapeutic approaches. Recently, we discovered two mechanisms that could generate fusion products without DNA rearrangement. One of the process is called “RNA trans-splicing”, whereby two separate RNAs can be spliced together and generate a fusion RNA, which then can be translated into a fusion protein. The other process involves two neighboring genes transcribing in the same direction, “cis-Splicing of Adjacent Genes (cis-SAGe). Our work on RNA trans-splicing and intergenic cis-splicing have posed a challenge to the traditional views and helped open a new paradigm for intergenic splicing processes that generate gene products in normal physiological conditions: even in the absence of physically “touching” each other, genes do send messages (messenger RNA) that can be mingled together.

Our long-term goals are to understand the scope of these phenomena, the physiological functions of these “intergenic splicing” process and their implications in both normal development and in cancer.

Other focuses of the lab are finding oncogene addiction events in glioblastoma (GBM), pediatric cancer, and breast cancer, developing novel drugs with minimal side effects.  Recently, we have discovered a new cancer-driving gene, AVIL. AVIL gene is highly expressed in all the GBMs, but hardly detectable in non-cancer control cells and tissues. We have accumulated strong preliminary data supporting the premises that AVIL is an Achilles heel of GBMs, to which glioblastoma cells are addicted: AVIL is not only needed for GBM cells to survive and for tumor to develop in animal xenograft models, its expression is also correlated with patient survival. I Studies of the mechanism and its oncogenic effect will not only help us better understand the disease, but also lead to better treatment options.

The Li lab is supported by:

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Funds for Excellence in Science and Technology
IVY Foundation Biomedical Innovation

 

4 thoughts on “Our Research

  1. Dear Dr. Li: Forgive me if this is not the right way to contact you, but the UVA website doesn’t seem to give me a better alternative.
    I am interested in the research, discussed in a press release today, showing genetic characteristics of glioblastoma. My father died of glioblastoma in 1989. My sister was diagnosed with glioblastoma in 2017, and an experimental treatment apparently knocked it out, so she is still here with negative MRI’s. But the fact that they both had a glioblastoma in essentially the same part of the brain has caused us to wonder about whether there is some genetic link at work, or whether it is simply unhappy coincidence. The popular accounts of your work with the AVIL gene shed no light for us. For obvious reasons, other family members very much want to know anything that can be known on this. Thank you in advance for any insights you can offer.

    • Hello Lloyd,

      Thank you for reaching out to me. I am sorry about your family members’ illness. It is a devastating disease both to the patients and their close relatives.

      I wonder if you have done whole genome sequencing to uncover potential mutations and structure variants. Genetic consular should provide you more information. I myself would want to know if your AVIL gene is intact. Since we just discovered the gene as a critical driver for GBM, there is not much known abut it. I am also not aware of any existing compounds targeting AVIL, or any clinical trials related to the gene. Sorry I can’t provide more insights.

      Best,

  2. Hi, we saw the article today about the work your lab is doing with glioblastomas. My mother had a glioblastoma removed a few weeks ago and we’re looking for clinical trials, are you running human trials or planning to start doing so soon?

    • Hello Katie,

      Thank you for reaching out to me. I am sorry for your mom’s illness. It is a devastating disease for patients and their close relatives.

      Since we just discovered the gene as a critical driver for GBM, there is not much known abut it. There is no current trials targeting AVIL, and I am also not aware of any existing compounds targeting AVIL. As a basic scientist, often times we have to wait for someone else to translate our discovery into clinical practice. However, this discovery prompted me to directly get involved in drug developing pipeline. As you may be aware, many oncogenes play key role in cancer, but not targetable. I am happy to report that AVIL is druggable, and we have a few lead compounds that showed promise. I do have to say that it is a long road ahead of us to get a final compound into clinical trial, which also requires a lot of resources. Please let her know that we are working hard on getting a treatment for her and other patients.

      Best,

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