Karen Guillemin

Assistant Professor of Biology

B.A., Harvard and Radcliffe Colleges;
Ph.D., Stanford University

Member of:
• Institute of Molecular Biology

Research Interests

All animals exist in intimate associations with communities of microorganisms that play important roles in the hosts’ normal development and physiology, and under certain circumstances can cause disease. In the Guillemin lab we investigate the molecular dialogues between bacteria and host cells that promote normal tissue development or cause pathology. Toward this goal our laboratory focuses on two experimental models. To understand the mechanisms by which intimate, long-term bacterial-host cell interactions can detrimentally alter host tissue programs of development and homeostasis, we study Helicobacter pylori, a pathogen of the human stomach that is associated with a number of diseases including gastric cancer. In order to understand the benefits that microbial associations confer on animals, we have pioneered a germ-free zebrafish model that allows us to precisely define the contributions of the resident microbiota to development of this model vertebrate.

Helicobacter pylori-host cell interactions

H. pylori has co-evolved with its human host and developed sophisticated mechanisms to adapt to and manipulate the niche of the human stomach. We study the molecular mechanisms employed by H. pylori to co-exist with host cells. One area of research investigates the molecular activities of the H. pylori secreted effector protein, CagA, which the bacterium translocates into host cells by means of a type IV secretion system. Within cultured human gastric epithelial cells, CagA causes dramatic changes in cell shape cell signaling pathways.

Figure 1: Human gastric epithelial (AGS) cells uninfected (left) or co-cultured with wild type (middle) or cagA mutant H. pylori (right).  Bacteria are in red and the cell cytoskeleton is in green. From Bourzac et al. (2007) Infect Immun.

To complement our analysis of CagA function in cell culture, we have developed a transgenic Drosophila model of CagA expression, which provides us with the ease of tissue-specific transgene expression combined with a wealth of genetic tools to study candidate host pathways and to discover novel genes affected by CagA signaling.

Figure 2: Scanning electron micrographs of Drosophila eyes from wild type (A), or transgenic animals expressing cagA, a single copy (B), two copies (C), with a dominant enhancing mutation (D) and with a dominant suppressing mutation (E). Images from Crystal Botham.

The role of the microbiota in zebrafish gut development

To study the mutualism between vertebrates and their associated microbial communities, or microbiota, we have developed a germ-free zebrafish model. Our analysis has revealed important roles for the gut microbiota in intestinal epithelial maturation, cell homeostasis and cell type specification, and the establishment of mucosal tolerance. We are currently investigating the molecular nature of the microbiota-derived signals that drive these developmental programs.

Figure 3: The gut associated microbiota of a zebrafish larva. Bacteria are in red, nuclei are in blue, and fish tissue is in green. Image from Julie Toplin.

Selected Publications

Bates JM, Akerlund J, Mittge E, Guillemin K. (2007) Intestinal Alkaline Phosphatase Detoxifies Lipopolysaccharide and Prevents Inflammation in Zebrafish in Response to the Gut Microbiota. Cell Host and Microbe, Vol 2, 371-382

Baltrus DA, Guillemin K, Phillips PC. (2007) Natural transformation increases the rate of adaptation in the human pathogen Helicobacter pylori. Evolution Int J Org Evolution. [Epub ahead of print]

Baden KN, Murray J, Capaldi RA, Guillemin K. (2007) Early developmental pathology due to cytochrome c oxidase deficiency is revealed by a new zebrafish model. J Biol Chem. 282(48):34839-49

Bourzac, K. M., C. M. Botham, and K. Guillemin. (2007) Helicobacter pylori CagA Induces AGS Cell Elongation through a Cell Retraction Defect That Is Independent of Cdc42, Rac1, and Arp2/3. Infect Immun 75:1203-13.

Cheesman, S. E., and K. Guillemin. (2007) We know you are in there: Conversing with the indigenous gut microbiota. Res Microbiol 158:2-9.

Rader, B. A., S. R. Campagna, M. F. Semmelhack, B. L. Bassler, and K. Guillemin. (2007) The quorum sensing molecule AI-2 regulates motility and flagellar morphogenesis in Helicobacter pylori. J Bacteriol. 189(17):6109-17.

Baltrus, D. A., and K. Guillemin. (2006) Multiple phases of competence occur during the Helicobacter pylori growth cycle. FEMS Microbiol Lett 255:148-55.

Bates, J. M., E. Mittge, J. Kuhlman, K. N. Baden, S. E. Cheesman, and K. Guillemin. (2006) Distinct signals from the microbiota promote different aspects of zebrafish gut differentiation. Dev Biol 297:374-86.

Bourzac, K. M., L. A. Satkamp, and K. Guillemin. (2006) The Helicobacter pylori cag pathogenicity island protein CagN is a bacterial membrane-associated protein that is processed at its C terminus. Infect Immun 74:2537-43.

Mouery, K., B. A. Rader, E. C. Gaynor, and K. Guillemin. (2006) The Stringent Response Is Required for Helicobacter pylori Survival of Stationary Phase, Exposure to Acid, and Aerobic Shock. J Bacteriol 188:5494-500.

Bourzac, K. M., and K. Guillemin. (2005) Helicobacter pylori-host cell interactions mediated by type IV secretion. Cell Microbiol 7:911-9.

Guillemin, K., N. R. Salama, L. S. Tompkins, and S. Falkow. (2002) Cag pathogenicity island-specific responses of gastric epithelial cells to Helicobacter pylori infection. PNAS U S A 99:15136-15141.

Salama, N., K. Guillemin, T. K. McDaniel, G. Sherlock, L. Tompkins, and S. Falkow. (2000) A whole-genome microarray reveals genetic diversity among Helicobacter pylori strains. PNAS U S A 97:14668-73.