Prof. Sheu’s research interest focuses on identification and characterization of tumor-associated genes by using genomewide technologies and functional studies. In the past years, he had defined Rsf-1, also known as HBXAP, as a potent cancer-driving gene during cancer development and progression . Significantly, Dr. Sheu demonstrated the interaction between Rsf-1 and SNF2H as the key for promoting oncogenic signaling in cancer cells, resulting in gross tumor growth  and drug resistance . These findings enable Rsf-1 as an attractive target for new therapy development . In recent years, Dr. Sheu’s studies further pointed out that Rsf-1 overexpression serves as a selecting barrier to allow outgrowth of cell clones with genetic defects in self-surveillance , that subsequently ease cancer cells to accumulate more genetic alterations . Similar mechanism was found applicable for BRAF oncogenic mutations at caner initiation stage . Achievements of those studies made Dr. Sheu won “Marquis Who’s Who in the World” in 2013, and the National Science Council (now the Ministry of Science and Technology) “Academic Research Award-Wu-Da-You Memorial Award” in 2014.
In addition to functional characterization of Rsf-1, Dr. Sheu initiated his studies on head and neck cancer including oral squamous cell carcinoma (OSCC) and nasopharyngeal carcinoma (NPC). Based on comparative analyses between genomic and transcriptome maps, Dr. Sheu has successfully validated EGFR activation, either through gene amplification/overexpression or activation of down-stream targets, is the most frequent genetic event in OSCC . On the other hand, deletion of 3p12.3-p14.2 and amplification of 3q26.2-q26.32 serve as genomic markers for advanced NPC , which might be the footprints of frequent Epstein-Barr virus reactivation . Based on above findings, Dr. Sheu found LRIG1, a negative regulator for EGFR signaling, as a tumor suppressor in head and neck cancer through down-regulation of EGFR ligands and extracellular remodeling activity . Using similar approach, Dr. Sheu also identified TLN1 amplification/over- expression responsible for OSCC migration and invasion, thus could be utilized as a good therapeutic target . Furthermore, Rsf-1  and haptoglobin  were found as valuable biomarkers for predicting clinical outcome and tumor recurrence of OSCC.
Other interesting findings regarding cancer-driving genes in head and neck cancer are under preparation for paper submission. For examples, we recently discovered a novel keratin fusion event in OSCC by NGS technology. Several fusion isoforms were defined and some of them were found correlated with worse clinical outcome [ROC and US patents][15, 16]. We are currently studying biofunctions of these fusion types to see if keratin fusion could be a newly defined mechanism for squamous cell transformation and cancer development. With the working experiences on tumor-associated genes, Dr. Sheu therefore holds the knowledge and key techniques/materials to define the oncogenic signaling networks of newly defined oncogenes.