Education
- B.A. Biology, University of North Carolina at Greensboro, 2000-2003
- Ph.D. Chemistry, North Carolina State University, 2004-2009
- American Cancer Society Postdoctoral Fellow, University of Illinois at Urbana-Champaign, 2009-2013
Biographical Sketch
Robert W. Huigens III received his bachelors in biology from the University of North Carolina at Greensboro in 2003 where he first developed an interest in organic synthesis and medicine. Robert went on to pursue his graduate studies in organic chemistry at North Carolina State University under the direction of Christian Melander. During his time at North Carolina State University, Robert started the biofilm program in the Melander lab while evaluating the biofilm inhibition and dispersal activity of several libraries of ageliferin-inspired small molecules he had synthesized. In 2009, Robert completed his Ph.D. in chemistry and went on to become an American Cancer Society postdoctoral fellow at the University of Illinois at Urbana-Champaign under the guidance of Paul Hergenrother. As a postdoctoral fellow in the Hergenrother lab, Robert developed a rapid approach to generate complex and diverse small molecules from commercially available natural products using various ring-distortion reactions for high-throughput screens in drug discovery efforts. In 2013, Robert joined the Medicinal Chemistry Department at the University of Florida as an assistant professor. His research interests include organic synthesis, drug discovery, chemical biology and bacterial pathogenesis.
Research Interests
In recent decades, we have discovered that free-swimming planktonic bacteria use various signaling molecules to monitor their cellular density and control certain bacterial behaviors in a process known as quorum sensing. Under the control of quorum sensing, bacteria are able to simultaneously attach to a surface and encase themselves in a protective matrix of biomolecules known as a biofilm. The National Institutes of Health has stated that ~80% of all bacterial infections are biofilm associated. Biofilms enable bacteria to thrive in hostile environments as biofilm mediated infections are highly resistant to host immune responses and conventional antibiotic treatments. Currently, no clinical agents have been developed that effectively target quorum sensing or biofilm machinery. To exacerbate this problem, many pharmaceutical companies have abandoned their antibacterial drug discovery programs due to a lack of success in recent years.
The overarching goals of the Huigens lab are to develop novel small molecules that can be used in the treatment of biofilm mediated bacterial infections and define proteins involved in highly regulated biofilm processes. Developing tomorrow’s therapeutic agents to combat bacterial biofilms is highly impactful to human health as drug-resistant bacterial infections have become a serious global problem. Students and postdoctoral fellows in our group will receive training at the interface of chemistry and biology using a combination of synthetic organic chemistry, medicinal chemistry, chemical biology, and microbiology approaches.
Keywords: medicinal chemistry, drug discovery, organic synthesis, chemical biology, quorum sensing, bacterial biofilm, bacterial pathogenesis
Representative Publications
Huigens III, R.W.; Morrison, K.C.; Hicklin, R.W.; Flood Jr., T.A.; Richter, M.F.; Hergenrother, P.J. “A ring-distortion strategy to construct stereochemically complex and structurally diverse compounds from natural products.” Nature Chemistry, published online 1-20-2013, DOI: 10.1038/NCHEM.1549.
Huigens III, R.W.; Reyes, S.; Reed, C. S.; Bunders, C.; Rogers, S.A.; Steinhauer, A.T.; Melander, C. “The chemical synthesis and antibiotic activity of a diverse library of 2-aminobenzimidazole small molecules against MRSA and multidrug-resistant A. baumannii.” Bioorg. & Med. Chem. 2010, 18, 663-674.
Rogers, S.A.; Huigens III, R.W.; Melander, C. “A 2-aminobenzimidazole that inhibits and disperses gram-positive biofilms through a zinc-dependent mechanism.” J. Am. Chem. Soc. 2009, 131, 9868-9869.
Huigens III, R.W.; Rogers, S.A., Steinhauer, A.T., and Melander, C. “Inhibition of Acinetobacter baumannii, Staphylococcus aureus, and Pseudomonas aeruginosa biofilms with a class of TAGE-triazole conjugates.” Org. Biomolec. Chem. 2009, 7, 794-802.
Huigens III, R.W.; Ma, L.; Gambino, C.; Moeller, P.D.R.; Basso, A.; Cavanagh, J.; Wozniack, D.J.; Melander, C. “Control of bacterial biofilms with marine alkaloid derivatives.” Mol. BioSys. 2008, 4, 614-621.
Huigens III, R.W.; Richards J.J.; Parise, G.; Ballard, T.E.; Zeng, W.; Deora, R.; Melander, C. “Inhibition of Pseudomonas aeruginosa biofilm formation with bromoageliferin analogues.” J. Am. Chem. Soc. 2007, 129, 6966-6967.