Center Directors:
Lawrence Marnett, Ph.D.
Richard Caprioli, Ph.D.
Daniel Liebler, Ph.D.
The Problem:
The word protein originates from the Greek word “prota”, meaning “of primary importance.” Protein molecules are involved in every cellular process within all living organisms, and their normal functions are prerequisites for the health of a cell. Once protein abnormality occurs, it can lead to cancer. Anti-cancer drugs often kill cancer cells by targeting those proteins that have undergone changes during cancer development.
Each human cell produces thousands of proteins that interact with each other. The collection of these proteins is known as the proteome. With the help of advance technologies, scientists can now study the intrinsic and complex nature of protein interactions in large scale to understand, in a more complete scope, the protein network. Research of the proteome is called proteomics.
Many new anti-cancer therapeutic agents have been discovered in recent years, contributing greatly to saving the lives of cancer patients. In many cases, however, the protein targets of these drugs are unknown, and how these drugs work inside the human body is not fully understood. Scientists need this critical information to monitor drug efficacy and toxicity in the human body.
The Solution:
The NFCR Center for Proteomics and Drug Actions at Vanderbilt University was established to address these challenges. Directed by Dr. Laurence Marnett and co-directed by Drs. Richard Caprioli and Daniel Liebler, this powerful research team consists of three leading scientists in the field. They will conduct research and obtain knowledge on how drugs are distributed and interact with their protein targets in cancer cells and normal tissues. The knowledge gained will enable scientists to develop new anti-cancer drugs with higher specificity and lower side effects.
The Research:
Anti-cancer drugs typically bind to their protein targets loosely. In other words, when researchers try to isolate and identify these drug targets, their success rate is very low. Dr. Marnett’s lab has successfully developed new techniques to manipulate the structure of the drug agents and make them bind to their protein targets more tightly, thus forming stable drug-target complexes and make it easier to detect and analyze the targets. Once the targets are identified and analyzed, scientists can manipulate the structure of the drugs to improve its anti-cancer function, reduce its side effects caused by the “off-target” interactions and discover more target proteins for further anti-cancer drug development.
At the NFCR Center for Proteomics and Drug Actions, Dr. Marnett will focus on the investigation of chemical methodology to produce chemical probes that are able to “fish out” protein targets of new drugs and make the targets easy to be detected by molecular analyzing and imaging equipment. Dr. Liebler will develop new targeted proteomics analytical methods to detect and analyze the “captured” protein targets. Dr. Caprioli will develop methodology for imaging drug-target complexes in targeted tissues as a measure of efficacy and toxicity. Finally, Drs. Liebler and Caprioli will jointly develop new methods and novel bioinformatics tools to analyze all the data from research projects in the center. The combined expertise of the three leading scientists will allow this NFCR Center to make significant contributions to cancer proteomics research and novel anti-cancer drug development.