Dr. Xuefeng Liu is a professor in Departments of Pathology (primary), Urology (secondary), and Radiation Oncology (secondary), and a member of The Molecular Carcinogenesis and Chemoprevention (MCC) Program at The Ohio State University Comprehensive Cancer Center (OSUCCC). His research focuses on mechanisms of bypassing cell senescence with oncogenic-viruses or cellular telomerase related pathways, and leads to discoveries of novel non-canonical functions of hTERT protein and a novel cell culture technology. This cell technology was licensed to a start-up biotechnology company, Propagenix, which is commercializing both the diagnostic as well as regenerative medicine applications. Dr. Liu has published more than 130 peer-reviewed articles in highly respected journals, including NEJM, Nature Protocols, PNAS, PLoS Pathogens, JVI, JBC, JMV, AJP. Currently, research areas in Liu laboratory (HPV and Cell Reprogramming Laboratory) include:
1. We developed a new cell culture method (conditional reprogramming, CR) that allows prolonged propagation of patient-derived normal and tumor cells for precision medicine (AJP, PNAS, NEJM, JCI, Nature Protocols, etc.). CR technology has been used by approximately 50 academic centers and 6 biorepositories (including NCI). CR and organoid cultures represent the next generation of patient-derived cell models. These in vitro systems have been described and highlighted in the NCI precision medicine initiative. They are being used for human cancer model initiative (HCMI) with ATCC and PDMR (patient-derived model repository) at NCI. CR media and CR cells have been distributed by Propagenix, StemCell Technology, Fisher Scientific, ATCC, etc. Using CR and organoid cultures, we study: (A) Generation of patient-derived cell models for CRPC study using CR and CDX technologies. (B) Biological factors underlying disparities of breast, prostate, lung, and GI cancers in African American using patient-derived cell models. (C) A novel non-invasive, cheap, and comfortable strategy to predict efficacy of treatments and recurrence of bladder cancer. (D). Longitudinal patient-derived cell models of bladder cancer for studying tumor heterogeneity and mechanisms of therapy response and resistance. (E) Patient-derived cancer models of HPV/EBV associated Head and Neck Squamous Cell Carcinomas (HNSCC) for studying cancer initiation and mechanisms of therapy response and resistance. (F) Patient-derived or individualized tumor micro-environment and personalized cancer vaccines. (G) Roles of cytoskeleton, AIB1, and BMI1 in regulation of conditional reprogramming and cell senescence.
2. We found that E6 and E7 from high risk HPVs induce immortalization through non-telomere/non-catalytic functions of hTERT (PLoS Pathogens 2013, JMV 2022). This finding has far-ranging implications for understanding the conversion of cells to an immortalized state. This new concept will not only help to shape the direction of future HPV biology studies, the information gained from such studies will define new domains of hTERT as targets for anti-viral and anti-cancer therapy. We will study: (A) HPV E6/E7, and targeting E6/E7 for therapeutics; (B) hTERT and non-canonical functions of telomerase, targeting hTERT protein and tumor microenvironment; (C) Targeting Myc pathways and tumor microenvironment epigenetically, and targeting E6/Myc interactions for treating HPV associated human cancer. (D) Biological mechanisms of cell aging and cancer initiation, especially roles of telomerase and telomeres in these processes.
3. High risk HPV E6 targets p53 for degradation, this may play a critical role in HPV induced carcinogenesis. However, our data demonstrated that p53 degradation by E6 is not required for cell immortalization. As we also described in Myc/Y-27632 system, p53 protein level and localization are not altered. This also is true in conditionally reprogrammed cells (CRCs). Recently, we found a role of delta133 p53 in the regulation of hTERT and cell immortalization (Cell Death & Dis. 2018). We are also studying the role of p53 and its splicing variants during conditional reprogramming and immortalization.
