Yonghe Li, Ph.D.

Biography

Dr. Yonghe Li received his B.S. in Pharmacology from Shanghai Medical University in China and his Ph.D. in Biochemistry from James Cook University in Australia. He completed his postdoctoral training in cell biology at Washington University School of Medicine in St. Louis. After working for three years as a Research Instructor at Washington University, Dr. Li joined Southern Research in 2005.

Research Interests

Dr. Li's laboratory is interested in the roles of the low density lipoprotein (LDL) receptor family members and their related proteins in biological systems and in malignant diseases. The LDL receptor family consists of over ten endocytic receptors, all of which share homology with the LDL receptor. Studies in the past several years have demonstrated that members of the LDL receptor family function not only in receptor-mediated endocytosis, but also in transducing signals that are important during embryonic development and the pathogenesis of human diseases.

The long-term goal of the laboratory is to identify new targets for anticancer small molecules. There are two major research projects underway. The first one aims to define the roles of LRP5/6 in Wnt signaling and tumorigenesis. The Wnt signaling pathway is involved in various differentiation events during embryonic development and when aberrantly activated, can lead to tumor formation. The LDL receptor-related protein-5 and 6 (LRP5 and LRP6) are two novel members of the expanding LDL receptor family. Recent studies have demonstrated that LRP5 and LRP6 are indispensable elements of the Wnt signaling pathway because of their interaction with several components of the pathway. Dr. Li's laboratory recently found that stable expression of LRP6 in human fibrosarcoma HT1080 cells enhances cell proliferation in vitro and tumorigenesis in vivo as a result of cytosolic ß-catenin accumulation and activation of Wnt signaling. It was also found that Mesd, a newly identified chaperone for members of the LDL receptor family, can function as a receptor antagonist by inhibiting ligand binding to mature LRP6 at cell surface.

The second research project conducted in Dr. Li's laboratory involves defining the roles of LRP1B in urokinase receptor signaling and tumorigenesis. LRP1B is a recently identified putative tumor suppressor protein that is frequently inactivated in several types of human cancer. This protein shares high homology with LDL receptor-related protein (LRP), and is therefore named LRP1B. Both LRP and LRP1B are large members (600 kDa) of the expanding LDL receptor family. In addition, several receptors in the family regulate endocytosis and regeneration of the urokinase plasminogen activator receptor. Urokinase receptor is essential for cell-surface associated plasminogen activation, and plays a critical role in cancer cell migration and metastasis. Recent studies in this lab demonstrate that despite overlapping ligand-binding specificity, LRP1B exhibits a significantly slower rate of endocytosis than LRP. As a result, expression of LRP1B prevents the regeneration of urokinase receptors at the cell surface and inhibits cell migration. Currently, the lab is studying molecular and cellular mechanisms by which LRP1B suppresses urokinase receptor function in human cancer cells and examining how changes in LRP1B expression influence cancer cell behaviors.