Living cells contain dynamic mixtures of macromolecules (such as proteins) and small molecules (such as phospholipids). Although the interactions among macromolecules have been extensively explored, the studies on small molecules are limited. We are interested in studying endogenous, small molecule-protein interactions and their downstream signaling. Multidisciplinary techniques, including those in organic synthesis, molecular, and cell biology, will be combined to answer questions related to human diseases, particularly cancer and neurodegenerative diseases. Currently, we are working on the following specific projects:

1. Phosphoinositide (PI) signaling: Inositol phospholipids (PIs) are a family of anchoring lipids with different combinations of phosphate groups around the inositol ring. Due to their functions of membrane recruitment and activation of downstream effector proteins, PIs are among the most versatile regulatory small molecules. They play diverse roles in cell signaling, cell motility, vesicle transport and development. Dys-regulation of PI signaling has been implicated in numerous diseases such as cancers and diabetes. We will generate tools to probe PI-protein interactions and diagnose and interfere with diseases related to PI signaling.

2. Chemistry and biology of S-adenosylmethionine (AdoMet): AdoMet is the major biological methyl donor and involved in many essential biochemical processes. We will develop methodologies to explore the novel applications of AdoMet in chemistry and to understand the effects of methylation in the biological systems.

3. Imaging and regulating PRL-3: phosphatase of regenerating liver 3 (PRL-3) has been found to be expressed at high levels in metastatic colorectal cancer but at low levels in non-metastatic tumors and normal colorectal epithelium. Over-expression of PRL-3 plays a potentially pathogenic role in human malignancies and PRL-3 is regarded as an attractive target for novel anticancer therapeutics and an important marker for metastatic tumors. However, little is known about the cellular roles of PRL-3. We will develop molecular probes and small molecule inhibitors of PRL-3 to understand and regulate its cellular biology.

4. Chemical approaches to small GTPase signaling: We will develop small-molecule regulators of small GTPases to regulate their signaling and probe their novel functions and mechanism of actions.