Profile

Our major focus has been to characterize the role of a new family of receptor tyrosine kinase (RTK), the Eph receptors and their ligands ephrins, in cancer metastasis and tumor angiogenesis. Our approach involves a combination of oncogenomics and proteomics, confocal microscopy and imaging, transgenic and knock out animal models, and traditional cell biology and biochemistry techniques.

Eph RTKs and their ligands are dysregulated in tumor tissues and expression of these molecules is associated with clinical outcome of various cancer type. In particular, EphA2 receptor plays critical roles in both tumor cells and tumor blood vessels. Our laboratory demonstrated that epithelial EphA2 is required for cell proliferation and tumor initiation. We also showed that vascular endothelial EphA2 promotes tumor progression through angiogenesis. As EphA2 regulates both tumor cells and host microenvironment, it is a good target for cancer therapy. Several anti-EphA2 agents have been developed and some of those are under clinical trials.

Current projects in the lab include:

  1. Role of ephrin-A1, the ligand for EphA2 RTK, in tumor metabolism in breast cancer.
  2. EphA2 in K-Ras and TKI-resistant EGFR mutant lung cancer and cancer stem cells.
  3. Dissecting opposing roles of EphA2 and EphA3 in lung cancer.
  4. Regulation of angiocrine signaling in tumor progression, metastasis, and stem cell function.


Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. B Cell-Intrinsic mTORC1 Promotes Germinal Center-Defining Transcription Factor Gene Expression, Somatic Hypermutation, and Memory B Cell Generation in Humoral Immunity. Raybuck AL, Cho SH, Li J, Rogers MC, Lee K, Williams CL, Shlomchik M, Thomas JW, Chen J, Williams JV, Boothby MR (2018) J Immunol 200(8): 2627-2639
    › Primary publication · 29531165 (PubMed) · PMC5893413 (PubMed Central)
  2. The receptor tyrosine kinase EphA2 promotes glutamine metabolism in tumors by activating the transcriptional coactivators YAP and TAZ. Edwards DN, Ngwa VM, Wang S, Shiuan E, Brantley-Sieders DM, Kim LC, Reynolds AB, Chen J (2017) Sci Signal 10(508)
    › Primary publication · 29208682 (PubMed) · PMC5819349 (PubMed Central)
  3. Implications of the differing roles of the β1 and β3 transmembrane and cytoplasmic domains for integrin function. Lu Z, Mathew S, Chen J, Hadziselimovic A, Palamuttam R, Hudson BG, Fässler R, Pozzi A, Sanders CR, Zent R (2016) Elife
    › Primary publication · 27929375 (PubMed) · PMC5207772 (PubMed Central)
  4. Eph Receptor Tyrosine Kinases in Tumor Immunity. Shiuan E, Chen J (2016) Cancer Res 76(22): 6452-6457
    › Primary publication · 27811149 (PubMed) · PMC5290221 (PubMed Central)
  5. LIM-Only Protein 4 (LMO4) and LIM Domain Binding Protein 1 (LDB1) Promote Growth and Metastasis of Human Head and Neck Cancer (LMO4 and LDB1 in Head and Neck Cancer). Simonik EA, Cai Y, Kimmelshue KN, Brantley-Sieders DM, Loomans HA, Andl CD, Westlake GM, Youngblood VM, Chen J, Yarbrough WG, Brown BT, Nagarajan L, Brandt SJ (2016) PLoS One 11(10): e0164804
    › Primary publication · 27780223 (PubMed) · PMC5079595 (PubMed Central)
  6. mTORC1 and mTORC2 in cancer and the tumor microenvironment. Kim LC, Cook RS, Chen J (2017) Oncogene 36(16): 2191-2201
    › Primary publication · 27748764 (PubMed) · PMC5393956 (PubMed Central)