Xiangbing Meng, PhD

Research Associate Professor of Pathology

Introduction

New prognosis biomarkers and potential therapeutic targets in gynecology; Synthetic lethal studies in gynecology; Mitotic Catastrophe induction in ovarian and endometrial cancer

Current Positions

Research Associate Professor of Pathology

Education

BS in Biochemistry, Beijing Normal University, China
MS in Biochemistry and Molecular Biology, Beijing Normal University, China
PhD in Biochemistry and Molecular Biology, Beijing Institute of Radiation Medicine, Academy of Military Medicine, Beijing, China
Postdoctoral Fellow in Biochemistry and Molecular Biology, Wright State University, Dayton, Ohio
Postdoctoral Fellow in Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, New Mexico

Graduate Program Affiliations

Biomedical Science (Cancer Biology)

Research Interests

Genomic instability is a major driving force for tumorigenesis. I am interested in the molecular mechanisms contributing to proliferation and cell death defects in cancers and the translation of these studies for the possible target therapies to specifically induce cell death or to modulate the cellular responses to DNA damage to increase cancer treatment efficacy in cancers affecting women, especially endometrial cancer and ovarian cancer. BCCIP (BRCA2 and CDKN1A Interacting Protein) is an example of a molecule involved in genomic stability maintenance. Our studies have shown that BCCIP regulates DNA repair and cell cycle regulation through BRCA2 and p21(CDKN1A) associated process. I have many years of experience studying BCCIP in many forms of human cancers. YRIC/AEG-1/ MTDH is a novel BCCIP interacting protein. LYRIC/AEG-1/MTDH is located at chromosome 8q22 whose overexpression has been linked to carcinogenesis in solid cancers such as breast, prostate, brain cancers and melanoma. Targeting LYRIC/AEG-1/MTDH has been found to enhance chemotherapy efficacy and reduce metastasis risk simultaneously in various types of solid tumors. Our research in Iowa has demonstrated that LYRIC/AEG-1/MTDH is over-expressed in endometrial cancer tissues but is not detected in normal endometrial tissues. Knockdown of LYRIC/AEG-1/MTDH can increase sensitivity of chemotherapy and targeted therapy such as death receptor TRAIL (Tumor necrosis (TNF)-related apoptosis-inducing ligand) mediated apoptosis in endometrial cancer cells. Novel functions of MTDH in the cytoplasm as an RNA binding protein and microRNA regulator have been observed in our lab. Effects of MTDH on cell cycle regulation were also confirmed. We also observed the reduction of LYRIC/AEG-1/MTDH protein level in endometrial cancer cell lines after HDAC inhibitor or Topoisomerase I inhibitor Camptothecin treatment. Finally, MTDH depletion in endometrial cancer cells greatly inhibits the tumor growth in xenograft mice. Biological function of MTDH will be studied in MTDH knockout mouse model. The effects of knockout of MTDH on the development of endometrial cancer will be done using conditional MTDH and PTEN double knockout mice, deleting these proteins specifically in the endometrium. We will study the mechanism of LYRIC/AEG-1/MTDH reduction after these drug treatments in endometrial cancer and ovarian cancer and test whether LYRIC/AEG-1/MTDH can be developed as potential therapeutic target. After getting enough preclinical data, we will cooperate with clinical physicians to develop translational studies. We have published three papers.
Synthetic lethality screening for therapeutic targets is an alternative approach to discover new therapeutic targets that are essential only in the context of specific cancer-causing mutations. We will pursue the use of a taxane plus a small molecule inhibitor of EGFR as a strategy to treat advanced or a recurrence of endometrial and ovarian cancer, which are under-studied and for which no substantial treatment advances have been made in the past three decades. Furthermore, a triple angiogenesis inhibitor, BIBF1120, which can simultaneously target VEGFR,FGFR and PDGFR has been observed to increase mitotic cell death by co-treatment with paclitaxel in our preclinical studies. We also observed the activation of mitosis kinase, PLK1. Furthermore, inhibiting the critical kinase of mitosis in this pathway, PLK1, with a single agent resulted in a similar therapeutic effect in p53 null cells as using paclitaxel plus a molecular inhibitor as described above. Molecular inhibitors to target cell cycle regulators chk1 or Wee1 will be used to increase sensitivity to chemotherapy. Our preclinical study will lead to clinical trial in IOWA for endometrial and ovarian cancer patients by directly targeting PLK1 or combination of small molecular inhibitors of Wee1, chk1 with chemotherapy

Selected Publications

Li, Y., Huang, C., Kavlashvili, T., Fronk, A., Zhang, Y., Wei, Y., Dai, D., Devor, E. J., Meng, X., Thiel, K. W., Leslie, K. K. & Yang, S. (2020). Loss of progesterone receptor through epigenetic regulation is associated with poor prognosis in solid tumors. American journal of cancer research 10 (6) 1827-1843. PMID: 32642294. PMCID: PMC7339273.
Bi, J., Areecheewakul, S., Li, Y., Yang, S., Zhang, Y., Ebeid, K., Li, L., Thiel, K. W., Zhang, J., Dai, D., Salem, A. K., Leslie, K. K. & Meng, X. (2019). MTDH/AEG-1 downregulation using pristimerin-loaded nanoparticles inhibits Fanconi anemia proteins and increases sensitivity to platinum-based chemotherapy. Gynecologic Oncology 155 (2) 349-358. DOI: 10.1016/j.ygyno.2019.08.014.
Bi, J., Yang, S., Li, L., Dai, Q., Borcherding, N., Wagner, B. A., Buettner, G. R., Spitz, D. R., Leslie, K. K., Zhang, J. & Meng, X. (2019). Metadherin enhances vulnerability of cancer cells to ferroptosis. Cell Death and Disease 10 (10). DOI: 10.1038/s41419-019-1897-2.
Meng, X., Yang, S., Zhang, J. & Yu, H. (2019). Contribution of alternative splicing to breast cancer metastasis. Journal of cancer metastasis and treatment 5. DOI: 10.20517/2394-4722.2018.96. PMID: 31737791. PMCID: PMC6857724.
Meng, X., Yang, S., Li, Y., Li, Y., Devor, E. J., Bi, J., Wang, X., Umesalma, S., Quelle, D. E., Thiel, W. H., Thiel, K. W. & Leslie, K. K. (2018). Combination of Proteasome and Histone Deacetylase Inhibitors Overcomes the Impact of Gain-of-Function p53 Mutations. Dis Markers eCollection 2018. DOI: 10.1155/2018/3810108. PMID: 30647797.
Meng, X., Bi, J., Li, Y., Yang, S., Zhang, Y., Li, M., Liu, H., Li, Y., McDonald, M. E., Thiel, K. W., Wen, K. K., Wang, X., We, M. & Leslie, K. K. (2018). AZD1775 Increases Sensitivity to Olaparib and Gemcitabine in Cancer Cells with p53 Mutations. Cancers (Basel) 10 (5). DOI: 10.3390/cancers10050149. PMID: 29783721. PMCID: PMC5977122.
Ebeid, K., Meng, X., Thiel, K. W., Do, A. V., Geary, S. M., Morris, A. S., Pham, E. L., Wongrakpanich, A., Chhonker, Y. S., Murry, D. J., Leslie, K. K. & Salem, A. K. (2018). Synthetically lethal nanoparticles for treatment of endometrial cancer. Nat Nanotechnol 13 (1) 72-81. DOI: 10.1038/s41565-017-0009-7.. PMID: 29203914. PMCID: PMC5762267 [Available on 2018-06-04].
Kavlashvilli, T., Jia, Y., Dai, D., Meng, X., Thiel, K. W., Leslie, K. K. & Yang, S. (2016). Inverse Relationship between Progesterone Receptor and Myc in Endometrial Cancer. PLoS One 11 (2) e0148912. DOI: 10.1371/journal.pone.0148912. PMID: 26859414. PMCID: PMC4747472.
Meng, X., Yang, S., Zhang, Y., Wang, X., Goodfellow, R. X., Jia, Y., Thiel, K. W., Reyes, H. D., Yang, B. & Leslie, K. K. (2015). Genetic Deficiency of Mtdh in Mice Causes Male Infertility via Impaired Spermatogenesis and Alterations in the Expression of Small Non-coding RNAs. J Biol Chm pii: jbc.M114.627653. PMID: 25787082.
Yang, S., Jia, Y., Liu, X., Winters, C., Wang, X., Zhang, Y., Devor, E. J., Hovey, A. M., Reyes, H. D., Xiao, X., Xu, Y., Dai, D., Meng, X., Thiel, K. W., Domann, F. E. & Leslie, K. K. (2014). Systematic dissection of the mechanisms underlying progesterone receptor downregulation in endometrial cancer. Oncotarget 5 (20) 9783-97. PMID: 25229191.