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L. Eric Huang

Associate Professor of Oncological Sciences and of Neurosurgery

M.D. Shanghai Medical University, China

Ph.D. Rutgers University

Research

References

eric.huang@hsc.utah.edu

Eric Huang's Lab Page

Eric Huang's PubMed Literature Search

Research

Our research efforts are directed towards understanding the mechanisms by which tumor cells become more and more malignant as they advance, a seemingly inevitable process that underlies therapeutic failure. Malignant progression involves genetic and epigenetic alterations that enable tumor cells to evolve and acquire aggressive malignant properties by activating various survival pathways. Although a great deal of efforts have been made to understand the resultant signaling pathways responsible for malignant progression, the mechanisms by which cancer cells acquire genetic and epigenetic changes in the first place remain obscure.

Our research focuses on the role of hypoxia (low oxygen tension) in malignant progression. Hypoxia is widespread in solid cancers and tightly associated with genetic alteration and resistance to chemotherapy and radiation therapy. Previous studies from our laboratory first demonstrated that the hypoxia-inducible factor 1 alpha (HIF-1alpha) (Huang and Bunn, 2003), a master regulator of oxygen homeostasis, induces genetic alterations by inhibiting DNA repair gene expression (Koshiji et al., 2005; To et al., 2006). At the molecular level, we identified a novel HIF-1alpha–c-Myc pathway (Huang, 2008; Koshiji et al., 2004) that accounts for the hypoxic suppression of DNA repair. To test our hypothesis that the HIF-1alpha–c-Myc pathway is crucial to genetic alterations that drive malignant progression (Huang et al., 2007), we have demonstrated that activation of the HIF-1alpha–c-Myc pathway alone is sufficient to accelerate tumor progression and metastasis using cell culture and mouse models (Hayashi et al., 2011; Yoo et al., 2011a; Yoo et al., 2011b).

Among various types of solid tumors including osteosarcomas and breast cancers, glioblastoma—the most frequently occurring and mostly deadly human intracranial tumor—is of our particular interest because of the presence of extreme hypoxia within the tumor and its salient feature of local infiltration. Immunohistochemical staining of human glioblastomas has revealed that HIF-1alpha is especially over-expressed in areas surrounding necrosis and at the peripheral where local invasion takes place. The objectives of our research, as illustrated in the figure, are to demonstrate a HIF-1alpha mediated mechanism of genetic and epigenetic alteration as the underlying cause of malignant progression; to biochemically characterize the molecular pathways of the underlying mechanism; and to develop a novel approach to cancer treatment by targeting the mechanism of malignant progression.

References