Research projects

The research programs in Dr. Huang’s laboratory focus on mechanisms of tumor progression, invasion and metastasis, and on effective therapeutic approaches. The laboratory has extensive research experience in molecular determinants of brain metastasis, in epigenetics mechanisms of glioma and cancer stem cell, and their impacts on cancer cell resistance to therapeutics.

Brain metastasis occurs in about 20% of all patients with cancer and is associated with poor survival.  The studies from the laboratory have yielded mechanistic insights into the roles of angiogenesis, invasion, and signaling pathways of brain metastasis. For example, we discovered for the first time that Stat3 plays a major role in the regulation of tumor invasion, angiogenesis, and brain metastasis. Moreover, we have identified the upstream signal transduction pathways leading to activation of Stat3 pathway.  Furthermore, we demonstrated the effectiveness of a Stat3 inhibitor WP1066 in controlling brain metastasis in a preclinical model of breast cancer brain metastasis. Moreover, the basic and translational knowledge of the mechanisms of brain metastasis gained from our research could provide guidance for the development of novel targeted therapies to combat this disease.

Research from the laboratory has determined the critical roles of the epigenetics mechanisms in gliomagenesis and cancer stem cell formation including gene transcriptional regulation, histone methylation and RNA m6A methylation. For examples, the Wnt/β-catenin signaling pathway is aberrantly activated in human cancers and is critical for cancer formation. A key feature of Wnt signaling activation is β-catenin nuclear localization, for which the underlying molecular mechanisms remain elusive. We showed that FoxM1 directly interacts with β-catenin and is necessary and sufficient for its nuclear localization and transcriptional activation in tumor cells. Our finding provides an improved understanding of the molecular mechanisms underlying β-catenin activation in tumors. We also interested in the roles of m6A RNA modification as well as long noncoding RNA in cancer development. We found that m6A demethylase ALKBH5 is required for the proliferation and tumorigenesis of glioma stem cells. Moreover, we identified FoxM1 as a key target of ALKBH5 which mediates ALKBH5’s function in glioma stem cells and discovered a long noncoding RNA that facilitates demethylation of FoxM1 nascent transcripts by ALKBH5. These significant findings were recently published in Cancer Cell and highlighted by the “Research Watch” of Cancer Discovery. These studies contribute to a better understanding of the molecular mechanisms that regulate the self-renewal and tumorigenic properties of glioma.

Current research involves studies epigenetics mechanisms of gene expression including histone methylation and ubiquitination, and RNA m6A methylation, and their impacts on cancer cell resistance to therapeutics.