P. Boon Chock, Ph.D.

Senior Investigator

Metabolic Regulation Section


Building 50, Room 2134
50 South Drive
Bethesda, MD 20814



Research Topics

The enzymatic activity of many proteins is regulated by covalent modifications. Research in Dr. Chock’s laboratory involves elucidating biochemical mechanisms of enzyme action and cellular regulation with a focus on the regulatory roles of reversible protein covalent modification. Dr. Chock is also interested in free radicals and reactive oxygen species-mediated oxidative modification of proteins and RNA. His work revealed the advantages of reversible covalent modification cascades in cell signaling in view of their enormous potential for signal and rate amplification and regulatory flexibility. He also showed the role of protein glutathionylation in regulating the activity of tyrosine phosphatase 1B and 2-Cys-peroxiredoxin, in growth factor-mediated actin polymerization, and in translocation.

Recently, Dr. Chock and his colleagues have been investigating cell signaling mechanisms by which bacterial toxins, such as Pasteurella multocida toxin (PMT), might promote carcinogenesis. In contrast to the well-accepted role of viruses in cancer, the involvement of bacteria in carcinogenesis remains controversial. PMT is an intracellular acting bacterial protein known for its potent mitogenic properties and its ability to induce anchorage-independent growth of certain cell types. These activities suggest that PMT may function as a tumor promoter, particularly in the case of chronic infections. Dr. Chock and colleagues have shown that PMT hijacks cell signaling pathways via deamidation of heterotrimeric G proteins. PMT also induces sustained mTORC1 activation via the Gαq/11/PLCβ/PKC pathway.

Dr. Chock’s laboratory also investigates familial amyotrophic lateral sclerosis (FALS). Missense mutations in Cu2+, Zn2+-superoxide dismutase (SOD1) are linked to FALS via a yet-to-be identified toxic gain-of-function. Dr. Chock and his colleagues have shown that the SOD1 mutants A4V and G93A exhibit a gain-of-function relative to their wild-type counterparts in the generation of free radicals. In their mechanistic study of FALS, they revealed that CCS (Cu2+ chaperone of the SOD1), in addition to its known copper chaperone activity, also functions as a molecular chaperone to facilitate the turnover of inactive FALS SOD1-linked aggregate via a macroautophagy pathway and induces mitochondrial translocation of inactive SOD1 mutants in AAV293 and HEK 293 cells. These results together with the CCS effects reported by others suggest that free radical generations may function as the initial event that leads FALS SOD1-linked aggregation, translocation, and degradation.

Oxidative stress has been linked to many diseases, and despite the emphasis on protein modifications resulting from an oxidative environment, nucleic acids are also vulnerable to oxidation. This is particularly true for RNA. Dr. Chock has turned his attention to studying the mechanisms of RNA oxidation and their physiological consequences. He and his colleagues have revealed that moderately oxidized mRNA exhibits a significant reduction in its translation fidelity despite the fact that oxidized mRNA shows a similar affinity for polysomes as its non-oxidized form.

Dr. Chock maintains an interest in developing new methods and theories applicable to biomedical research. Theoretical studies in his laboratory have demonstrated the effects of oscillations and energy-driven fluctuations on the dynamics of enzyme catalysis and free energy transduction. Furthermore, Dr. Chock and his colleagues have developed and applied electric field based methods to study membrane dynamics in cells and vesicles, apoptosis, and Ca2+ oscillation based signaling pathways.


P. Boon Chock received his Ph.D. in chemistry from the University of Chicago in 1967. After postdoctoral training with Manfred Eigen at the Max-Planck-Institut für Biophysikalische Chemie in Göttingen, Germany, Dr. Chock joined the Laboratory of Biochemistry at the NHLBI in 1971 as a visiting scientist. He was converted to a research chemist in 1973 and promoted to the Chief of the Metabolic Regulation section in 1981. Dr. Chock served as the Chief of the Laboratory of Biochemistry from 1994 to 2008, and the Director of the Biochemistry and Biophysics Center from 2002 to 2008. In 1993, Dr. Chock received the NIH Director’s Award. Dr. Chock has authored or coauthored more than 180 publications, including review articles and book chapters. Currently, he is a member of the editorial board of the Journal of Biological Chemistry and has previously served on the editorial boards of Archives of Biochemistry and Biophysics and BioFactors, and he was co-editor of Current Topics in Cellular Regulation Series from 1989 to 2000. Dr. Chock is a member of the American Chemical Society and the American Society for Biochemistry and Molecular Biology.

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This page was last updated on Thursday, January 3, 2013