Research Topics
The Xu Lab employs a multi-disciplinary approach including Single-Cell sequencing, Proteolysis targeting chimeric (PROTAC) technology, multiomics, biochemistry, organoid and in vivo mouse model to interrogate the regulation of the mitosis program by oncogenic signaling pathways in cancer cells, and explore new therapeutic strategies for targeting cancer aneuploidy and chromosome instability (CIN). Additionally, I have a long-term interest in translating basic research findings into clinical application to develop novel targeted therapies, gene therapies based on Adeno-associated virus (AAV) vector-mediated gene delivery or Lipid nanoparticles (LNP)-mediated mRNA delivery, and immunotherapies.
We are particularly interested in PI3K/AKT/PTEN pathway and KRAS pathway. Our disease focus is solid tumors with emphasis on breast cancer and prostate cancer.
We aim to utilize PROTAC degrader as a molecular probe to discover the previously overlooked function of interested proteins.
PROTAC degrader is a recently developed technology to degrade the target protein in a reversible way, which is superior to the traditional irreversible CRISPR knockout or RNAi technology. In addition, PROTAC degrader for kinase is always better than the parental kinase inhibitor to fully shut down the signaling pathway and inhibit the kinase for a long time, for instance, AKT degrader MS21. We will continue to develop more PROTAC compounds to target our interested oncogenic kinases, such as AKT, TGFβR, Notch, KRASG12D and et al, and investigate mechanisms for how these oncogenes drive cancer progression.
Xu Lab research will implement and integrate a comprehensive battery of high-throughput technologies including genomics sequencing, transcriptome profiling, proteomics analysis, and chemogenomic screening to 1) Understand the cancer genome, epigenome, and proteome with mechanistic studies, with a specific interest in mRNA alternative translation reshaping the proteome; 2) Integrative bioinformatics and functional characterization of genetic or epigenetics transformation in the process of breast and prostate cancer neuroendocrine differentiation; 3) Cancer disparity research in breast cancer and prostate cancer that disproportionally affect the Deep South, especially focus on Triple-Negative Breast Cancer (TNBC); 4) Investigate mechanisms of sensitivity and resistance to targeted therapies in cancers with specific genetic mutations, chemotherapy resistance in TNBC, and immunotherapy. 5) Discover the therapeutic vulnerability in specific subtypes of breast cancer with unmet needs in clinical treatment strategy.
Tumor suppressors play important role in protecting a cell from progression to cancer, for example, p53, pRb, PTEN. Their loss or inactivation is frequently implicated in multiple types of cancers, and experimental rescue of these tumor suppressors in cancer cells usually lead to cell death. However, clinically rescue of these tumor suppressors are often unsuccessful and lack of strategy. The major roadblock is lack of feasible delivery system to effectively deliver tumor suppressor proteins to the cancer cells. We recently developed an AAV- based gene therapy to deliver PTEN-long, a secreted isoform of PTEN tumor suppressor which plays an essential role in the PI3K signaling pathway and regulates cell proliferation and survival. It has shown promising tumor inhibition effect, and inspired us to further improve gene therapy delivering PTEN-Long and other tumor suppressors.
