Bingcheng Wang received his PhD degree in Toxicology and Oncology from University of Wisconsin-Madison in 1991, where he studied the crosstalk between oncogenes and tumor suppressor genes in breast cancer. For postdoctoral training he went to La Jolla, California at the Sanford-Burnham Institute to study cell adhesion and migration. In 1997 he was appointed to the faculty at Department of Medicine, MetroHealth Campus, Case Western Reserve University School of Medicine.
Research in the Wang laboratory focuses on the roles of Eph receptor tyrosine kinases in invasive growth and distal metastasis of cancer cells. The 14 members of Eph kinases are by far the largest subfamily of receptor tyrosine kinases in mammalian system. They interact with the membrane-anchored ligands called ephrins and mediate cell-cell contact signaling.
Over the past decade we have made several major contributions in unraveling the intricate interplays between Eph kinases and other cell regulatory pathways in controlling tumor etiology and malignant progression. Most recently, a novel reciprocal regulatory loop between EphA2 and Akt was discovered in glioblastoma and prostate cancer (Figure 1). The discovery revealed an intricate dichotomy of EphA2, which can either promote or suppress tumor progression, depending on the ligand occupancy status of EphA2. This body of work constitutes a significant part of our current understanding of Eph/ephrin system in cancer biology.
- Investigate molecular bases of EphA2-PI3K/Akt crosstalk in regulating tumor cell migration, invasion and metastasis.
- Evaluate how loss of ephrin-A expression, frequently observed in human cancers, may promote glioma invasion and prostate cancer metastasis in vivo using genetically engineered mouse models.
- Examine the regulation of progenitor properties of normal and tumor stem cells by Eph-ephrin bidirectional signaling.
- Develop novel Eph kinase-targeted agents the treatment of metastatic diseases. We are focusing on the optimization, preclinical testing, and clinical trials of novel small molecule EphA2 agonists that we have identified through computer-aided virtual screening and cell-based assays. One of the small molecules has shown promising effects on distal metastasis of prostate cancer in preclinical models, and is ready for human clinical trial in the near future.