Honglin Li, PhD

Assistant Professor of Pediatrics
Feinberg School of Medicine

Research Interests:
The Li laboratory is interested in dissection of molecular mechanisms that regulate cellular stress response and cell death signaling. Regulation of cell cycle and cellular response to DNA damage is critical for genome stability, normal tissue homeostasis, tumorigenesis and cancer treatment. Cells utilize cell cycle checkpoint mechanisms to ensure accurate transmission of genetic material. We have recently identified Cdk5 activator binding protein C53 as a novel regulator of cell cycle and DNA damage response. Our study demonstrated that C53 knockdown leads to cell cycle defects and resistance to genotoxin-induced apoptosis. C53 overexpression abolishes the G2/M checkpoint-mediated Cdk1 inactivation, thereby sensitizing cancer cells to various DNA damage agents. We also found that C53 knockdown results in delayed Cdk1 activation and mitotic entry, while C53 overexpression promotes premature Cdk1 activation. We are currently investigating how C53 modulates Cdk1 activation in normal cell cycle progression and DNA damage response. This study will provide insight into a novel regulatory mechanism for DNA damage-induced apoptosis. It will lay a foundation for further exploitation of this novel protein as a potential therapeutic target in cancer treatment. Cellular response to ER (endoplasmic reticulum) stress is another focus of the laboratory. Accumulation of misfolded proteins in the ER lumen induces a coordinated cellular response known as the ER stress response or unfolded protein response (UPR). ER stress response is involved in the pathogenesis of many human diseases, including neurodegenerative diseases, diabetes and certain liver and heart diseases. They have recently identified a novel protein complex that play an important role in ER stress response. We will further dissect the molecular mechanism by which this complex regulates ER stress response.

Selected Publications:
Jiang, H., Wu, J., He, C., Yang, W., Li, H. (2008) A tumor suppressor C53 protein antagonizes checkpoint kinases to promote cyclin-dependent kinase 1 activation. Cell Research.

Yang, W., Monroe, J., Zhang, Y., George, D., Bremer, E. and Li, H. (2006). Proteasome inhibition induces both pro- and anti-cell death pathways in prostate cancer cells. Cancer Lett 243, 217-27.

Jiang, H., Luo, S. and Li, H. (2005). Cdk5 activator-binding protein C53 regulates apoptosis induced by genotoxic stress via modulating the G2/M DNA damage checkpoint. J Biol Chem 280, 20651-9.

Wu, J., Luo, S., Jiang, H. and Li, H. (2005). Mammalian CHORD-containing protein 1 is a novel heat shock protein 90-interacting protein. FEBS Lett 579, 421-6.

Tong, X. and Li, H. (2004). eNOS protects prostate cancer cells from TRAIL-induced apoptosis. Cancer Lett 210, 63-71.