• Zhi Wen M.D. & Ph.D.

  • Associate Research Scientist


    • MCRI - MCRI-Precision Med Research
    • 1000 North Oak Ave. ML8 Marshfield, WI 54449
    • (715) 221-6444

Education

2004 to 2011:
Ph.D., Cancer Biology, University of Wisconsin-Madison, Madison, WI
1995 to 2000:
M.D., Clinic medicine, Central South University, Changsha, China

Work Experience

2021 to Present:
Associate Research Scientist, Marshfield Clinic Research Institute, Marshfield, WI
2013 to 2020:
post-doctoral/associate researcher, University of WIsconsin-Madison, Madison, WI
2011 to 2013:
Post doctor, MD Anderson Cancer Center/Biodesign Institute, Houstin, TX/Tempe, AZ
2000 to 2004:
Junior faculty member, Central South University, Changsha, China

Statement

Cancer biology and genetics
Zhi Wen, MD&PhD, uses multi-disciplinary techniques in molecular and cellular biology, OMICS methods, and animal models to address the roles of human tumor viruses in cancer initiation, the mechanisms by which long non-coding RNAs regulate cancer metastasis, and genetic predispositions of nuclear receptors to cancer. These projects in cancer biology and cancer prevention will be combined with the application of high-throughput drug screening approaches in translational studies to develop personalized chemotherapy in cancer. Dr. Wen’s research bridges the bench (laboratory), cage (animal models), computer (bioinformatics), and the bedside (translational research).

Research Interests

Current projects:
1. Roles of human tumor virus in initiation of hematopoietic malignancies. The MCHS information service supports Epidemiology studies and Genomics studies. We co-express viral oncogenes and genetic variants obtained from Whole exome sequencing of FFPE samples in blood cells as well as establishing transgenic mouse strains with Crispr/Cas9 technique. Our efforts will contribute to the cancer prevention.

2. Roles of long non-coding RNA (lncRNA) in colorectal cancer metastasis. We identified a lncRNA from whole transcriptome deep sequencing of a colorectal cancer cell line whose knock-down significantly inhibits the metastasis of colorectal cancer cells into liver in a cecum-injection mouse model. We are dissecting the underlying molecular mechanisms.

3. Genetic predisposition of Nuclear receptors to cancer. We established the interactions between nuclear receptors and p53. However, it has been overlooked, considering that p53 serves as the key tumor suppressor and that over 30% of FDA-approved drugs target nuclear receptors. We developed a p53 responsive report system to screen SNPs of nuclear receptors. Our system will not only contribute to the drug discovery but also provide experimental evidence to predict SNPs.

4. High throughput drug screening in cancer cell lines, patient samples and 3D organoid culture. We have a lot of experience in high throughput screenings using various libraries, including cDNA, RNAi, chemical and cell lines. Working closely with oncologists, we are doing drug repurpose screening in cell lines and patient samples in order to provide oncologists with the list of sensitive drugs and drug combo.

Professional Societies:
2021 - now, active member of AACR (American Association for Cancer Research)
2021 - now, active member of ASH (American Society of Hematology)
2005 - 2011, student member of ASV (American Society for Virology)

Presentations

2024:
Influence of aging, comorbidities, and chemotherapy on dementia in patients with metastatic cancer, American Society of Clinical Oncology (ASCO) 2024 Annual Meeting

Select Publications

  • Wen Z, Pyeon D, Wang Y, Lambert P, Xu W, Ahlquist P. Orphan nuclear receptor PNR/NR2E3 stimulates p53 functions by enhancing p53 acetylation. Mol Cell Biol. 2012 January; 32(1):26-35. doi: 10.1128/MCB.05513-11. PMCID: PMC3255696.
    PubMed ID: 22025681
  • Zhao Z, Wang L, Wen Z, Ayaz-Guner S, Wang Y, Ahlquist P, Xu W. Systematic analyses of the cytotoxic effects of compound 11a, a putative synthetic agonist of photoreceptor-specific nuclear receptor (PNR), in cancer cell lines. PLoS One. 2013 September; 8(9):e75198. doi: 10.1371/journal.pone.0075198. PMCID: PMC3774666.
    PubMed ID: 24066170
  • Damnernsawad A, Kong G, Wen Z, Liu Y, Rajagopalan A, You X,...Zhang J. Kras is Required for Adult Hematopoiesis. Stem Cells. 2016 July; 34(7):1859-71. doi: 10.1002/stem.2355. PMCID: PMC5358545.
    PubMed ID: 26972179
  • Kong G, You X, Wen Z, Chang YI, Qian S, Ranheim EA,...Zhang J. Downregulating Notch counteracts KrasG12D-induced ERK activation and oxidative phosphorylation in myeloproliferative neoplasm. Leukemia. 2019 March; 33(3):671-685. doi: 10.1038/s41375-018-0248-0. PMCID: PMC6405304.
    PubMed ID: 30206308
  • Xiaona You, Zhi Wen, Yuan-I Chang, Erik A. Ranheim, Yun Zhou, Lan Zhou,...Jing Zhang. Systemic Notch downregulation promotes Kras G12D -induced myeloproliferative neoplasm. [published online ahead of print 2019 March 31]. British Journal of Haematology. 186(3):e52-e56. doi: 10.1111/bjh.15893.
  • Yang K, Wu H, Zhang Z, Leisten ED, Nie X, Liu B,...Tang W. Development of Selective Histone Deacetylase 6 (HDAC6) Degraders Recruiting Von Hippel-Lindau (VHL) E3 Ubiquitin Ligase. ACS Med Chem Lett. 2020 April 9; 11(4):575-581. doi: 10.1021/acsmedchemlett.0c00046. PMCID: PMC7153272.
    PubMed ID: 32292566
  • Wen Z, Yun G, Hebert A, Kong G, Ranheim EA, Finn R,...Zhang J. Nras Q61R/+ and Kras-/- cooperate to downregulate Rasgrp1 and promote lympho-myeloid leukemia in early T-cell precursors. Blood. 2021 June 10; 137(23):3259-3271. doi: 10.1182/blood.2020009082. PMCID: PMC8351901.
    PubMed ID: 33512434
  • Wen Z, Rajagopalan A, Flietner ED, Yun G, Chesi M, Furumo Q,...Zhang J. Expression of NrasQ61R and MYC transgene in germinal center B cells induces a highly malignant multiple myeloma in mice. Blood. 2021 January 7; 137(1):61-74. doi: 10.1182/blood.2020007156. PMCID: PMC7808014.
    PubMed ID: 32640012
  • You X, Liu F, Binder M, Vedder A, Lasho TL, Wen Z,...Zhang J. Asxl1loss cooperates with oncogenic Nras in mice to reprogram immune microenvironment and drive leukemic transformation. [published online ahead of print 2021 October 26]. BLOOD. doi: 10.1182/blood.2021012519.
    PubMed ID: 34699595
  • Wen Z, Finn R, Gao X, Li L, Hebert A, Ranheim EA,...Zhang J. Tcof1 haploinsufficiency promotes early T cell precursor-like leukemia in NrasQ61R/+ mice. Leukemia. 2022 April;36(4):1167-1170. doi: 10.1038/s41375-022-01510-7. PMCID: PMC8983511.
    PubMed ID: 35082403
  • Flietner E, Wen Z, Rajagopalan A, Jung O, Watkins L, Wiesner J,...Zhang J. Ponatinib sensitizes myeloma cells to MEK inhibition in the high-risk VQ model. Sci Rep. 2022 June 23;12(1):10616. doi: 10.1038/s41598-022-14114-z. PMCID: PMC9226136.
    PubMed ID: 35739276
  • Flietner E, Yu M, Poudel G, Veltri AJ, Zhou Y, Rajagopalan A,...Zhang J [including Wen Z.] Molecular characterization stratifies VQ myeloma cells into two clusters with distinct risk signatures and drug responses. ONCOGENE. 2023 May; 42(21):1751-1762. doi: doi: 10.1038/s41388-023-02684-9.
    PubMed ID: 37031341
  • Sathipati S, Aimalla N, Tsai MJ, Carter T, Jeong S, Wen Z,...Ho SY [including Shukla SK.] Prognostic microRNA signature for estimating survival in patients with hepatocellular carcinoma. CARCINOGENESIS. 2023 December 2;44(8-9):650-661. doi: 10.1093/carcin/bgad062.
    PubMed ID: 37701974