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Xuefeng Liu, MD

Professor

Xuefeng Liu, MD

Phone:

614-688-8002

E-mail:

Email Dr. Liu

Mailing Address:

385E Wiseman Hall
400 W. 12th Ave.
Columbus, OH 43210

Biosketch

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.

Grants

Title: Conditionally Reprogrammed Cell Model for Castration-Resistant Prostate Cancer (CRPC)

Role: Principal Investigator

Sponsor: NIH R01CA222148


Title: Inhibition of castration resistant prostate cancer by targeting of the IKKbeta/AR signaling

Role: Co-Investigator

Sponsor: NIH R01 CA212094


Title: Validating Urine Derived Cancer Cells (UDCC) -- Non-Invasive and Living Liquid Biopsies -- in Bladder Cancer Clinics

Role: Principal Investigator

Sponsor: NIH R33CA258016


Title: Developing Functional Human Cell Models to Study Initiation and Progression of Prostate Cancer between AA and EA men

Role: Principal Investigator

Sponsor: NIH 1R01CA276474-01


Title: Targeting PI3Kalpha beta and the ErbB family of protein-tyrosine kinases in cisplatin-resistant head and neck squamous cell carcinomas (HNSCC)

Role: Co-Investigator

Sponsor: NIH R56DE030423-01A1

Academic and Medical Appointments

2022-Present Professor, Radiation Oncology (Secondary), The Ohio State University, Columbus, OH

2020-Present Professor, Department of Pathology (Primary), Department of Urology (Secondary), The Ohio State University

2014-2020 Director of Telomeres and Cell Immortalization Program, Co-Director, Center for Cell Reprogramming, Georgetown University Medical Center, Washington, DC

2003-2020 Assistant Professor, Associate Professor, Professor, Department of Pathology, Georgetown University Medical Center, Washington, DC

1996-1999 Associate Professor and Associate Director of Cell Biology, Institute of Virology, Hubei Medical University, Wuhan, China

Education and Training

2002-2003 Postdoctoral Fellow, Georgetown University, Washington, DC

2000-2002 Postdoctoral Fellow, NCI/NIH, Bethesda, MD

1999-2000 Postdoctoral Fellow, Emory University, Atlanta, GA

1988-1991 MS, Hubei Medical University, Wuhan, Chinas

1983-1988 MD, Hubei Medical University, Wuhan, China

Selected Publications

Search in PubMed

  • Liu L, Mondal AM, Liu X. Crosstalk of moderate ROS and PARP-1 contributes to sustainable proliferation of conditionally reprogrammed keratinocytes. J Biochem Mol Toxicol. 2023 Feb;37(2):e23262. doi: 10.1002/jbt.23262. Epub 2022 Nov 24.
  • Miller J, Dakic A, Spurgeo M, Saenz F, Kallakury B, Zhao B, Zhang J, Zhu J, Ma Q, Xu Y, Lambert P, Schlegel R, Riegel AT, Liu X. AIB1 Is A Novel Target of the High-Risk HPV E6 protein and A Biomarker of Cervical Cancer Progression. J Med Virol. 2022 Aug;94(8):3962-3977. doi: 10.1002/jmv.27795. Epub 2022 Apr 27. PMID: 35437795
  • Ci X, Hao J, Dong X, Xue H, Wu R, Choi SYC, Haegert AM, Collins CC, Liu X, Lin D, Wang Y. Conditionally Reprogrammed Cells from Patient-Derived Xenograft to Model Neuroendocrine Prostate Cancer Development. Cells. 2020 Jun 4;9(6):1398. doi: 10.3390/cells9061398. PMID: 32512818
  • Liu X, Mondal AM. Conditional cell reprogramming for modeling host-virus interactions and human viral diseases. J Med Virol. 2020 Nov;92(11):2440-2452. doi: 10.1002/jmv.26093. Epub 2020 Jun 16. PMID: 32478897
  • Wu Y, Ho W, Huang Y, Jin DY, Li S, Liu SL, Liu X, Qiu J, Sang Y, Wang Q, Yuen KY, Zheng ZM. SARS-CoV-2 is an appropriate name for the new coronavirus. Lancet. 2020 Mar 21;395(10228):949-950. doi: 10.1016/S0140-6736(20)30557-2. Epub 2020 Mar 6. PMID: 32151324
  • Casciano JC, Perry C, Cohen-Nowak AJ, Miller KD, Vande Voorde J, Zhang Q, Chalmers S, Sandison ME, Liu Q, Hedley A, McBryan T, Tang HY, Gorman N, Beer T, Speicher DW, Adams PD, Liu X, Schlegel R, McCarron JG, Wakelam MJO, Gottlieb E, Kossenkov AV, Schug ZT. MYC regulates fatty acid metabolism through a multigenic program in claudin-low triple negative breast cancer. Br J Cancer. 2020 Mar;122(6):868-884. doi: 10.1038/s41416-019-0711-3. Epub 2020 Jan 16. PMID: 31942031
  • Palechor-Ceron N, Krawczyk E, Dakic A, Simic V, Yuan H, Blancato J, Wang W, Hubbard F, Zheng YL, Dan H, Strome S, Cullen K, Davidson B, Deeken JF, Choudhury S, Ahn PH, Agarwal S, Zhou X, Schlegel R, Furth PA, Pan CX, Liu X. Conditional Reprogramming for Patient-Derived Cancer Models and Next-Generation Living Biobanks. Cells. 2019 Oct 27;8(11):1327. doi: 10.3390/cells8111327. PMID: 31717887
  • Jiang S, Wang J, Yang C, Tan R, Hou J, Shi Y, Zhang H, Ma S, Wang J, Zhang M, Philips G, Li Z, Ma J, Yu W, Wang G, Wu Y, Schlegel R, Wang H, Cao S, Guo J, Liu X, Dang Y. Continuous culture of urine-derived bladder cancer cells for precision medicine. Protein Cell. 2019 Dec;10(12):902-907. doi: 10.1007/s13238-019-0649-5. PMID: 31347094
  • Su S, Di Poto C, Roy R, Liu X, Cui W, Kroemer A, Ressom HW. Long-term culture and characterization of patient-derived primary hepatocytes using conditional reprogramming. Exp Biol Med (Maywood). 2019 Aug;244(11):857-864. doi: 10.1177/1535370219855398. Epub 2019 Jun 11. PMID: 31184925
  • Lin W, Yip YL, Jia L, Deng W, Zheng H, Dai W, Ko JMY, Lo KW, Chung GTY, Yip KY, Lee SD, Kwan JS, Zhang J, Liu T, Chan JY, Kwong DL, Lee VH, Nicholls JM, Busson P, Liu X, Chiang AKS, Hui KF, Kwok H, Cheung ST, Cheung YC, Chan CK, Li B, Cheung AL, Hau PM, Zhou Y, Tsang CM, Middeldorp J, Chen H, Lung ML, Tsao SW. Establishment and characterization of new tumor xenografts and cancer cell lines from EBV-positive nasopharyngeal carcinoma. Nat Commun. 2018 Nov 7;9(1):4663. doi: 10.1038/s41467-018-06889-5. PMID: 30405107
  • Li Z, Liao J, Yang Z, Choi EY, Lapidus RG, Liu X, Cullen KJ, Dan H. Co-targeting EGFR and IKKβ/NF-κB signalling pathways in head and neck squamous cell carcinoma: a potential novel therapy for head and neck squamous cell cancer. Br J Cancer. 2019 Feb;120(3):306-316. doi: 10.1038/s41416-018-0351-z. Epub 2018 Dec 26. PMID: 30585254
  • Mondal AM, Zhou H, Horikawa I, Suprynowicz FA, Li G, Dakic A, Rosenthal B, Ye L, Harris CC, Schlegel R, Liu X. Δ133p53α, a natural p53 isoform, contributes to conditional reprogramming and long-term proliferation of primary epithelial cells. Cell Death Dis. 2018 Jul 3;9(7):750. doi: 10.1038/s41419-018-0767-7. PMID: 29970881
  • Zhang Y, Dakic A, Chen R, Dai Y, Schlegel R, Liu X. Direct HPV E6/Myc interactions induce histone modifications, Pol II phosphorylation, and hTERT promoter activation. Oncotarget. 2017 Oct 25;8(56):96323-96339. doi: 10.18632/oncotarget.22036. eCollection 2017 Nov 10. PMID: 29221209
  • Liu X*, Krawczyk E, Suprynowicz FA, Palechor-Ceron N, Yuan H, Dakic A, Simic V, Zheng YL, Sripadhan P, Chen C, Lu J, Hou TW, Choudhury S, Kallakury B, Tang DG, Darling T, Thangapazham R, Timofeeva O, Dritschilo A, Randell SH, Albanese C, Agarwal S, Schlegel R*. Conditional reprogramming and long-term expansion of normal and tumor cells from human biospecimens. Nat Protoc. 2017 Feb;12(2):439-451. doi: 10.1038/nprot.2016.174. Epub 2017 Jan 26. PMID: 28125105 *corresponding author
  • Selvanathan SP, Graham GT, Erkizan HV, Dirksen U, Natarajan TG, Dakic A, Yu S, Liu X, Paulsen MT, Ljungman ME, Wu CH, Lawlor ER, Üren A, Toretsky JA. Oncogenic fusion protein EWS-FLI1 is a network hub that regulates alternative splicing. Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):E1307-16. doi: 10.1073/pnas.1500536112. Epub 2015 Mar 3. PMID: 25737553
  • Palechor-Ceron N, Suprynowicz FA, Upadhyay G, Dakic A, Minas T, Simic V, Johnson M, Albanese C, Schlegel R, Liu X. Radiation induces diffusible feeder cell factor(s) that cooperate with ROCK inhibitor to conditionally reprogram and immortalize epithelial cells. Am J Pathol. 2013 Dec;183(6):1862-1870. doi: 10.1016/j.ajpath.2013.08.009. Epub 2013 Oct 3. PMID: 24096078
  • Miller J, Dakic A, Chen R, Palechor-Ceron N, Dai Y, Kallakury B, Schlegel R, Liu X. HPV16 E7 protein and hTERT proteins defective for telomere maintenance cooperate to immortalize human keratinocytes. PLoS Pathog. 2013;9(4):e1003284. doi: 10.1371/journal.ppat.1003284. Epub 2013 Apr 4. PMID: 23592995
  • Yuan H, Myers S, Wang J, Zhou D, Woo JA, Kallakury B, Ju A, Bazylewicz M, Carter YM, Albanese C, Grant N, Shad A, Dritschilo A, Liu X*, Schlegel R*. Use of reprogrammed cells to identify therapy for respiratory papillomatosis. N Engl J Med. 2012 Sep 27;367(13):1220-7. doi: 10.1056/NEJMoa1203055. PMID: 23013073 *corresponding author