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:

NCI logo

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Funds for Excellence in Science and Technology
IVY Foundation Biomedical Innovation

 

12 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,

  3. Hi Dr Li,
    My husband was just diagnosed with a grade 4 glioblastoma. He is not able to have surgery as the tumor is too deep in his brain. I saw your article last week and of course this gave me hope. I know it’s new but I’m praying something happens to give him some hope to fight this. He starts radiation and chemo this week. Is there a way we can follow your findings and any updates?

    • Hi Hannah,

      Sorry to hear about your husband’s illness. I wish we have had something for him already. Unfortunately, there is still a long way to go before our discovery can be translated into clinical practice. We will publish our results as we make more discoveries and progresses. We will try to update our website as frequent as we can. Thank you and hope your husband will do well in his treatment!

  4. Dr. Li, many thanks to you and your lab for the magnificent discovery about the link between AVIL and GBM. Like Katie and Lloyd, I have a loved one impacted by GBM. My wife would be most interested in a Phase 1 trial regarding your research on AVIL.
    Godspeed Dr. Li,
    Chad

    • Hi Chad,

      I am really sorry for your wife’s unfortunate encounter with GBM. At this moment, there is no clinical trial targeting AVIL. The lab people are all committed to work hard and speed up the research. We hope that someday soon our work can save lives in clinic.

  5. Dear Dr Li,
    This is really great news. We have a lead cancer drug that is very effective on GBM. We are very close to starting a Phase1b/2 for pancreatic, GBM and brain mets. Kiyatec in Greenville, SC did some work for us and the compound did very well against 3 GBM pdx’s under their 3d ex vivo platform, even the one that was TMZ resistant. If you can contact me, we will provide our compound for your lab to see if our compound can hit the AVIL target, too If so, we are very far down the line and could help accelerate your research. Thank you and good luck!
    Todd Robinson
    trobinson@rokitpharma.com

  6. Dr. Li,

    My mother is days away from passing away from Glioblastoma Multiforme. Her wish was to be donated for medical advances. Can you direct me to the best place for brain donation? We live in Nashville Tn.

    Thank you so much.
    Lori

    • Dear Lori,

      I am so sorry for your mother’s illness. I admire her courage and applaud her willingness to donate her brain to help research. Her legend will live on. Vanderbilt University should be a good choice.

      Best,

      Li lab

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