Selection of proteins with desired functions from the natural proteome libraries and synthetic protein libraries

The Liu lab uses in vitro protein selection strategies to address biological problems on a proteome-wide scale. The major tool used in the lab is a novel technique called mRNA display, in which a protein is covalently linked to the 3' end of its own mRNA. Because of this physical link, mRNA display provides a rapid and powerful means of identifying protein-protein interactions by amplifying or enriching for interacting proteins based on functional characteristics. Our research interests focus on the following fields:

1. Deciphering the signaling pathways mediated by proteases and by Ca2+ using systems biology approaches. We address the problems using mRNA-displayed proteomes from human, mouse, Drosophila, and C. elegans. Current projects in the lab include: (a) to identify the family member-specific natural substrate repertoire of different caspases and granzymes; (b) to decipher the signaling pathways of several regulatory proteins identified from the selection; and (C) to identify potential drug targets that are involved in the pathogenesis of cancer and neurodegenerative diseases.
2. Developing novel protein therapeutics that can be used in tumor diagnosis and treatment. We use molecular evolution approaches to develop novel antibody mimics, on the basis of the scaffolds of several stable protein domains and non-mammalian antibodies, that bind to biomarkers on the surface of cancer cells. We conjugate these target-binding antibody mimics to small molecule drugs or nanoparticles for the targeted delivery of therapeutic agents.
3. Identifying the protein targets of drugs or drug candidates whose action mechanisms are unknown. We combine molecular proteomic and chemical biology approaches to identify the protein targets of drugs whose target-binding affinities are modest. Current project in this field is a collaborative effort with the Kohn lab to identify the targets of anti-epilepsy drug lacosamide from the proteome of mouse.

The Liu lab is at Division of Medicinal Chemistry and Natural Products at the School of Pharmacy. The lab is also affiliated to the Carolina Center for Genome Sciences and the Carolina Center of Cancer Nanotechnology Excellence. The projects in the Liu lab are funded by the National Institute of Neurological Disorders and Stroke, the American Cancer Society, the National Cancer Institute, and the National Institute of Diabetes and Digestive and Kidney Diseases.