Zhi Wen M.D. & Ph.D.
Associate Research Scientist
MCRI - MCRI-Precision Med Research
1000 North Oak Ave. ML8 Marshfield, WI 54449
- 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
- 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
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).
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.
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)
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
Xiaona You, Fabao Liu, Moritz Binder, Alexis Vedder, Terra L Lasho, Zhi Wen,...Jing Zhang. 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
Zhi Wen, Remington Finn, Xin Gao, Lin Li, Alexander Hebert, Erik A. Ranheim,...Jing Zhang. Tcof1 haploinsufficiency promotes early T cell precursor-like leukemia in NrasQ61R/+ mice. [published online ahead of print 2022 January 26]. Leukemia. doi: 10.1038/s41375-022-01510-7.
Evan Flietner, Zhi Wen, Adhithi Rajagopalan, Oisun Jung, Lyndsay Watkins, Joshua Wiesner,...Jing Zhang. Ponatinib sensitizes myeloma cells to MEK inhibition in the high-risk VQ model. Scientific Reports. 2022 June 1; 12(10616)doi: https://doi.org/10.1038/s41598-022-14114-z.
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.
PubMed ID: 35739276