UCSF

Craik receives Protein Society’s Emil Thomas Kaiser Award

Charles S. Craik, PhD, faculty member in the School’s Department of Pharmaceutical Chemistry, has been named the 2016 recipient of the Protein Society’s Emil Thomas Kaiser Award.

The Kaiser award is given annually by the international society to recognize “a recent, highly significant contribution to the application of chemistry in the study of proteins.” The society advances the multi-disciplinary scientific study of proteins—the complex molecules expressed by genes that carry out the functions of life.

In announcing the award, which will be conferred in July at the society’s 30th anniversary symposium in Baltimore, the organization cited Craik’s world-renowned research into proteolytic enzymes (proteases), which break apart other proteins and are directly or indirectly involved in virtually every biological function underlying health or disease.

The society lauded Craik for “providing a better understanding of the chemical make-up and the biological importance of these critical proteins to aid in the rapid detection, monitoring, and control of infectious diseases and cancer.”

As his department colleague, William DeGrado, PhD, recipient of the society’s 2015 Stein and Moore Award, wrote in support of Craik’s nomination: “His extensive work on characterization and inhibition of … disease related proteases constitutes a major area of biomedically important achievement. … Dr. Craik has published more than 280 papers, many of them classics that have been cited hundreds of times.”

Craik also serves as director of both the UCSF PhD graduate program in Chemistry and Chemical Biology (CCB) and the Quantitative Biosciences Consortium, which brings together five UCSF PhD graduate programs, including CCB, under one umbrella. He holds 11 U.S. patents, and co-founded Catalyst Biosciences and Alaunus Biosciences.

More about Craik’s work on protease enzymes

Present in all organisms, proteases comprise the second-largest class of enzymes—proteins that accelerate chemical reactions. Humans have more than 600 types of them. They cleave the peptide bonds that link amino acids in other proteins, irreversibly changing them. Yet the target proteins (substrates) and biological functions of most proteases are not known.

Among the Craik Lab achievements cited by the Protein Society is the development of new tools and methods to rapidly determine the particular protein targets (specificity) of such uncharacterized enzymes, a process dubbed deorphanization. Craik’s approach uses synthetic peptides (short chains of 14 amino acids) that sample all 20 amino acids in adjacent and near-adjacent positions. When cleaved by a protease, the peptide sequences, identified by mass spectrometry, act like partial license plate numbers to identify the protein substrates the protease acts upon and where it cleaves them.

KSHV protease monomer

The molecular surface of the dimer interface of a KSHV protease monomer including key residues and helices. The partner monomer is omitted.

Another major Craik focus noted by the society is the structural and functional analysis of the protease vital to the Kaposi’s sarcoma-associated herpes virus (KSHV), which causes the most common cancer in patients with AIDS. Finding that two of the enzymes must come together to activate, research in his lab is developing leads for drugs that disrupt that protein-protein interface by binding to an alternative (allosteric) site. Such a treatment may target similar proteases to more effectively treat all nine human herpes viruses, including cytomegalovirus (which can cause disabling and life-threatening illnesses in infants and immune-compromised patients) and those causing diseases such as shingles, mononucleosis, and genital herpes.

Indeed, in the late 1980s, Craik led a UCSF team which demonstrated that the selective inhibition of the protease enzyme in HIV, the virus that causes AIDS, would be an effective treatment. In the ensuing decades, pharmaceutical companies developed protease inhibitors to treat HIV as well as the hepatitis C virus.

In another major recent application of proteolytic analysis, the Craik Lab helped identify the increased activation of a protease called matriptase as a marker for several cancers and engineered selective antibodies for detection of its active form. And in current work, Craik and his colleagues are developing compounds to non-invasively (non-surgically) detect and differentiate among different types of pancreatic disease and cancers—a vital step toward improving early detection, status evaluation, and patient survival—based on the activity of a particular family of proteolytic enzymes.
 


About the School: The UCSF School of Pharmacy is a premier graduate-level academic organization dedicated to improving health through precise therapeutics. It succeeds through innovative research, by educating PharmD health professional and PhD science students, and by caring for the therapeutics needs of patients while exploring innovative new models of patient care. The School was founded in 1872 as the first pharmacy school in the American West. It is an integral part of UC San Francisco, a leading university dedicated to promoting health worldwide.

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