- 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
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 (i.e., “Complexity-to-Diversity”). 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, medicinal chemistry, antibacterial agents and personalized cancer therapeutics.
The overarching goal of the Huigens lab is to develop novel small molecules that can be used in the treatment of drug-resistant bacterial infections and cancers. We currently have three major areas of research in the Huigens lab which are discussed in further detail below. Students and postdocs in our group will receive training at the interface of chemistry and biology using a combination of synthetic organic chemistry, medicinal chemistry, chemical biology, microbiology and cancer biology approaches.
1) Drug Discovery of Small Molecule Antibiofilm Agents
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. Our lab is currently pursuing the chemical synthesis of novel antibiofilm agents based on natural product leads.
2) Identification of Novel Antibacterial Agents
Our group is actively pursuing the identification of novel antibacterial agents. Our goals are to develop novel small molecules that are highly potent and clinically useful against multidrug resistant pathogenic bacteria such as S. aureus, S. epidermidis, P. aeruginosa, A. baumannii and M. tuberculosis. There is a desperate need for new and effective clinical agents to combat these pathogens. We are currently using whole-cell screens to evaluate small molecules synthesized in our labs against several bacterial pathogens to identify lead compounds for further development. Our group is also involved in a dynamic collaboration using virtual screening and molecular modeling approaches to identify lead structures for synthesis and biological evaluation.
3) Development of Personalized Cancer Treatments
Historically, compounds that have demonstrated potent toxicity against the largest number of cancer cell lines have been considered excellent leads for further development as anticancer agents. As a result, anticancer treatments heavily rely on cytotoxic molecules that hit cellular targets critical to all rapidly dividing cell types. Cancer patients receiving generally cytotoxic agents during treatments experience severe side effects. Although generally cytotoxic anticancer agents are valuable, compounds demonstrating selectivity for cancerous cells or a single cancer-type have potential to become personalized cancer treatments with greatly reduced or eliminated side effects. A major goal towards developing personalized cancer treatments is to identify anticancer agents that are highly potent against cancerous cells due to the effective targeting of a cellular protein critical to the cancer that is overexpressed in cancerous cells and not overexpressed in normal cell types. Currently we are involved in developing personalized cancer treatments for leukemia patients using whole-cell screening approaches of small molecules synthesized in our lab. Additionally, we are developing novel small molecule inhibitors of cancer-driving enzymes that are overexpressed in various cancers based on virtual screening approaches.
Keywords: medicinal chemistry, drug discovery, organic synthesis, chemical biology, antibacterial agents, antibiofilm agents, anticancer agents, personalized cancer treatments
Huigens Group Members
Professor Robert W. Huigens III – Principle Investigator
Nicholas Borrero, Ph.D. – Postdoctoral Fellow (Ph.D. Chemistry; University of Florida)
Nicholas Paciaroni, B.S. – Graduate Student (B.S. Chemistry; Clemson University)
Aaron Garrison, B.S. – Graduate Student (B.S. Biochemistry; University of South Florida)
Cristian Perez – Undergraduate Researcher (Chemistry Major)
Benjamin Duong – Pharmacy Student/Summer Researcher (5/2013 to 8/2013)
University of Florida Affiliations
1) Emerging Pathogens Institute (EPI)
2) UF Health Cancer Center
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 Chem. 2013, 5, 195-202.
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.
Melander, C.; Cavanagh, J.; Ritchie, D.; Huigens III, R.W.; Ballard, T.E.; Richards, J.J.; Lindsey, J.S. “Inhibition of biofilms in plants with imidazole derivatives.” Patent No. 8,278,340; Issued 10/2/2012.
Melander, C.; Rogers, S.A.; Huigens III, R.W.; Reed, C.S. “Inhibition and dispersion of bacterial biofilms with imidazole-triazole derivatives.” Patent No. 7,897,631; Issued 3/1/2011.
Melander, C.; Cavanagh, J.; Huigens, R.W.; Ballard T.E.; Richards, J.J. “Inhibition of bacterial biofilms with imidazole derivatives.” Patent No. 7,906,544; Issued 3/15/2011.