The Clinical-Translational Seminar Series -Dr. Dara Frank

(Above) Dr. Dara Frank met with graduate students in the Clinical Translational Seminar and Readings in Pathology Course.

On October 12, 2012, Dr. Dara Frank visited the CRND and delivered a fascinating lecture on her lab's penetration of the opportunistic strategies of a pathogen, which is responsible for significant morbidity and mortality in humans and animals. Dr. Frank's seminar, "Molecular and Cellular Analyses of the Pseudomonas aeruginosa Cytotoxin, ExoU" further illuminated the work she described a 2011 paper outlining her team's discovery of the role of Ubiquitin in the toxic effects of P. aeruginosa (Anderson et al., Molecular Microbiology 82(6) 1454-1467). Graduate students of Drs. Patricia Champion and Shaun Lee had read Frank's paper in preparation for the study's principal investigator's visit. Dr. Frank is a Professor of Microbiology and Molecular Genetics at the Medical College of Wisconsin and the Director, Center for Infectious Disease Research.

Dr. Frank's research is focused on the interaction between hosts and bacterial factors involved in infections with Pseudomonas aeruginosa and Francisella tularensis. She explores the genetic regulation of exotoxin synthesis, examining the relationship between the expression of toxins (e.g., toxins injected into eukaryotic cells that compromise the innate immunity in hosts), the pathogenesis of the bacterium, and host responses.

In her seminar, Dr. Frank described the process by which the common bacterium, P. aeruginosa, carries the effector protein, ExoU, in an inactivated state where it cannot harm the bacterium. Once the bacterium infects a host cell, however, a protein in the host, Ubiquitin, activates ExoU and allows it to degrade the membrane of the host's eukaryotic cells. Commenting on Dr. Frank's seminar, Dr. Shahir Rizk praised her "very elegant experiment" for demonstrating that the host protein is indeed required for the toxic effect of this dangerous bacterial protein to take effect.

Pseudomonas aeruginosa is an opportunistic pathogen found in skin flora, as well as soil, water, and a variety of human environments. In humans and animals with compromised immunity, the bacterium may gain entry and colonize body organs with potentially fatal consequences. In medical facilities, the bacterium may be found in medical equipment or implements and have disastrous results, particularly in the case of biofilms of P. aeruginosa, which are particularly resistant to treatment with antibiotics.

Dr. Frank's lab played a leading role in the discovery and characterization of the "P. aeruginosa type III system," which mediates the delivery of toxins. Her lab continues to explore enzyme inhibitors, antibody reagents, and vaccines, which may potentially neutralize these damaging toxins.

(Above) Dr. Frank enjoyed a walk on the Notre Dame campus with Dr. Patricia Champion, course instructor, and Dr. Shahir Rizk (following) of the Center for Rare and Neglected Diseases. (Photos, Stackowitz, 2012)





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