Assistant Professor, Department of Molecular and Human Genetics

Ph.D., Universite libre de Bruxelles, 1996
Postdoc, Massachussets Institute of Technology, 1997
Postdoc, University of California at San Francisco, 2004

RESEARCH INTERESTS:

Cells are defined by membrane boundaries that regulate the selective exchange of matter and information between aqueous environments. The plasma membrane, a universal feature of all cells, contains about one-third of the total protein in the cell and plays important biological roles in processes ranging from signal transduction to energy metabolism. Studies on the heat shock response led to the discovery of a new class of proteins, heat shock proteins, comprised of chaperones and proteases which are crucial constituents of the cellular machinery for protein folding, repair, and degradation. Despite our rather detailed understanding of how chaperones and proteases function in the cytoplasm, we are only beginning to understand cellular processes involved in the maintenance of membrane protein integrity. It has become clear that the molecular chaperones and proteases play a key role in sensing changes in the physiology of the cell. My long-term research goal is to understand how the cell monitors and responds to the state of proteins in the membrane, and how membrane proteins can sense and transduce signals from the plasma membrane into the cytoplasm.

The major focus of my work is FtsH, a membrane-anchored metallo-protease, which functions as a master regulator in E. coli. FtsH is the only ATP-dependent protease that is essential for growth, as well as the only universally conserved ATP dependent protease in bacteria. It degrades both cytoplasmic and integral membrane proteins. Among its regulatory substrates are the heat shock factor G³², which sets the transcription rate of the heat shock genes themselves, the cII and cIII proteins of bacteriophage l, which control the developmental outcome of phage infection, and LpxC, an enzyme, involved in membrane biogenesis. In addition, FtsH performs a housekeeping function, degrading unassembled membrane proteins such as unassembled SecY translocase and the unassembled subunit of the F0 component of the ATP synthase. Finally, FtsH functions as a crucial protease in organisms as diverse as bacteria, plants, and humans. For example, inactivation of the human FtsH orthologue causes neurodegeneration in hereditary spastic paraplegia.

My recent work showed that the mode of action of FtsH protease differs from that of the cytoplasmic proteases characterized thus far. Cytoplasmic ATP proteases unfold and degrade virtually any protein that bears a suitable recognition tag. In contrast, FtsH discriminates between potential substrate proteins based jointly on recognition signals and on thermodynamic stability. Thus, degradation by FtsH requires not only recognition, but also suitable unfolding properties by its substrates. This finding represents a new paradigm for the mechanism of an ATP dependent protease, and open new lines of investigation.

SELECTED PUBLICATIONS:

1. Kobiler O, Oppenheim A, Herman C (2004). Recruitment of host ATP dependent proteases by bacteriophage Lambda. J. Struct. Biol. 146: 72-78.

2. Herman C, Prakash S, Zen L, Matouschek A, Gross CA (2003). Lack of a robust unfoldase confers a unique level of substrate specificity to the universal AAA protease FtsH. Mol. Cell 11: 659-669.

3. Wang JD, Herman C, Tipton KA, Gross CA, Weissman JS (2002). Directed evolution of substrate-optimized GroEL/S chaperonins. Cell 111: 1027-1039.

4. Herman C, Gross CA (2000). Heat stress. In Encyclopedia of Microbiology, Academic Press, Vol. 2: 598-606.

5. Herman C, Thévenet D, Bouloc P, Walker GC, D’Ari R (1998). Degradation of the carboxy-terminal-tagged cytoplasmic proteins by the Escherichia coli protease HflB (FtsH). Genes Dev. 12: 1348-1355.

6. Herman C, D’Ari R (1998). Proteolysis and chaperones: The destruction/reconstruction dilemma. Curr. Opin. Microbiol. 1: 204-209.

For more publications, see listing on Pub Med.

CONTACT INFORMATION:

Christophe Herman, Ph.D
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza Rm. S909A
Houston, Texas 77030, U.S.A.
Mail Stop: BCM225

Phone: 713-798-2126
Fax:
E-mail:

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