Seminar:

Profile: Erin E. Carlson received her B.A. at St. Olaf College (Northfield, MN) in 2000. She went on to graduate studies funded by the NIH Predoctoral Biotechnology Training Program at the University of Wisconsin - Madison and earned a Ph.D. in organic chemistry in 2005 under the direction of Professor Laura L. Kiessling. Her graduate career focused on the design and synthesis of mechanistic probes and inhibitors for carbohydrate-binding proteins, concentrating on the study of UDP-galactopyranose mutase (UGM), an enzyme involved in cell wall biosynthesis of Mycobacterium tuberculosis.

Subsequently, Dr. Carlson was awarded an American Cancer Society Postdoctoral Fellowship for studies at The Scripps Research Institute with Professor Benjamin F. Cravatt. Carlson and Cravatt developed a global metabolite profiling strategy that utilizes chemoselective probes to enable enrichment and profiling of metabolites from complex biological systems. This technology, referred to as Metabolite Enrichment by Tagging and Proteolytic Release (METPR), facilitates the rigorous characterization of biochemical pathways through their most sensitive reporter, endogenous small molecules. In 2007, Dr. Carlson received an NIH Pathway to Independence Award (K99/R00) and joined the faculty at Indiana University in 2008. In the summer of 2014, she joined the faculty in the Chemistry Department at the University of Minnesota and was appointed as a Graduate Faculty member of the Department of Medicinal Chemistry, the Department of Biochemistry, Molecular Biology and Biophysics and the graduate program in Biomedical Informatics and Computational Biology in 2015.

Since the start of her independent career, she has won numerous awards including being named a Presidential Early Career Awards for Scientists and Engineers (PECASE) recipient, a Pew Biomedical Scholar, the NIH Director’s New Innovator Award, the Indiana University Outstanding Junior Faculty Award, the NSF CAREER Award, the Cottrell Scholar Award and was named a Sloan Research Fellow and an Indiana University Dean's Fellow. Professor Carlson has been highlighted in several videos including one produced by NBC in their Science Behind The News series, a fast-paced video series supported by the National Science Foundation. This piece was one of five videos highlighting work funded by NSF's Directorate for Mathematical and Physical Sciences. She was also featured in a "Brilliant Minds" video. Dr. Carlson was also named one of "Tomorrow's PIs" in the sixth annual issue of Genome Technology and received the Outstanding Postdoctoral Mentor Award from the University of Minnesota Postdoctoral Association in 2017.

Abstract: Pseudomonas aeruginosa infections have reached a "critical" threat status making novel therapeutic approaches required. Inhibiting key signaling enzymes known as the histidine kinases (HKs), which are heavily involved with its pathogenicity, has been postulated to be an effective new strategy for treatment. Herein, we demonstrate the potential of this approach with benzothiazole-based HK inhibitors that perturb multiple virulence pathways in the burn wound P. aeruginosa isolate, PA14. Specifically, our compounds significantly reduce the level of toxic metabolites generated by this organism that are involved in quorum-sensing and redox-balancing mechanisms. They also decrease the ability of this organism to swarm and attach to surfaces, likely by influencing their motility appendages. Quantitative transcription analysis of inhibitor-treated cultures showed substantial perturbations to multiple pathways including expression of response regulator GacA, the cognate partner of the “super regulator” of virulence, HK GacS, as well as flagella and pili formation. These promising results establish that blocking of bacterial signaling in P. aeruginosa has dramatic consequences on virulence behaviors.