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UF Health University of Florida
Department of Medicinal Chemistry College of Pharmacy
Research Overview

Huigens Laboratory

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 Huigens received his bachelors in Biology from the University of North Carolina at Greensboro in 2003.  He then pursued graduate studies in Chemistry at North Carolina State University under the direction of Professor Christian Melander. After earning his Ph.D. in 2009, he went on to become an American Cancer Society postdoctoral fellow at the University of Illinois at Urbana-Champaign under the guidance of Professor Paul Hergenrother. In 2013, Dr. Huigens joined the Medicinal Chemistry Department at the University of Florida as an assistant professor. His research interests include organic synthesis, drug discovery, medicinal chemistry, chemical biology, antibacterial agents and personalized cancer therapeutics. Recently, Dr. Huigens was the recipient of two Young Investigator Awards from the American Chemical Society (Division of Medicinal Chemistry) and the Center for Biofilm Engineering (Montana State University) for his group’s discovery of novel bacterial biofilm-eradicating agents.

Research Interests

The overarching goal of the Huigens lab is to push back the boundaries of drug discovery using new and innovative strategies to tackle unmet challenges associated with complex molecule synthesis, drug-resistant bacteria and cancer. Students and postdocs in our group receive training at the interface of chemistry and biology using a combination of synthetic organic chemistry, medicinal chemistry, chemical biology and microbiology approaches. We currently have three major areas of research (click on the link below for more on our research programs):

Huigens Group Members

Professor Robert W. Huigens III – Principal Investigator
Alejandra Chavez-Riveros (Ph.D. Chemistry; UNAM, Mexico City)
Srinivasarao Tenneti (postdoctoral fellow; 2019-present)
Chip Norwood – Graduate Student (B.S. Chemistry; East Tennessee State University)
Hongfen Yang – Graduate Student (M.S. Chemistry; Chinese Academy of Sciences)
Ke Liu (medicinal chemistry graduate student; 2018-present)
Cayle Gao (undergraduate researcher; 2018-present)

University of Florida Affiliations

  1. Chemistry Department (courtesy faculty appointment)
  2. Center for Natural Products, Drug Discovery and Development (CNPD3)
  3. Emerging Pathogens Institute (EPI)
  4. UF Health Cancer Center

Huigens Lab Publications

  • Abouelhassan, Y.; Zhang, Y.; Jin, S.; Huigens III, R. W. “Transcript Profiling of MRSA Biofilms Treated with a Halogenated Phenazine Eradicating Agent: A Platform for Defining Cellular Targets and Pathways Critical to Biofilm Survival.” Angew. Chem. Int. Ed., accepted 9-19-2018. DOI: 10.1002/anie.201809785 and 10.1002/ange.201809785
  • Garrison, A. T.; Abouelhassan, Y.; Kallifidas, D.; Tan, H.; Kim, Y. S.; Jin, S.; Luesch, H.; Huigens III, R. W. “An Efficient Buchwald-Hartwig/Reductive Cyclization for the Scaffold Diversification of Halogenated Phenazines: Potent Antibacterial Targeting, Biofilm Eradication and Prodrug Exploration.” J. Med. Chem., just accepted.
  • Yousaf, H. H.; Garrison, A. T.; Abouelhassan, Y.; Basak, A.; Jones, J. B.; Huigens III, R. W. “Identification of Nitroxoline and Halogenated Quinoline Analogues with Antibacterial Activities against Plant Pathogens.” ChemistrySelect 2017, 2, 6235-6239.
  • Basak, A.; Abouelhassan, Y.; Zuo, R.; Yousaf, H.; Ding, Y.; Huigens III, R. W. “Antimicrobial Peptide-Inspired NH125 Analogues: Bacterial and Fungal Biofilm-Eradicating Agents and Rapid Killers of MRSA Persisters.” Org. Biomol. Chem. 2017, 15, 5503-5512. Cover Art Selection
  • Yang, H.; Abouelhassan, Y.; Burch, G. M.; Kallifidas, D.; Huang, G.; Yousaf, H.; Jin, S.; Luesch, H.; Huigens III, R. W. “A Highly Potent Class of Halogenated Phenazine Antibacterial and Biofilm-Eradicating Agents Accessed Through a Modular Wohl-Aue Synthesis.” Sci. Rep. 2017, 7, 2003.
  • Abouelhassan, Y.; Basak, A.; Hussain, Y.; Huigens III, R. W. “Identification of N-Arylated NH125 Analogues as Rapid Eradicating Agents against MRSA Persister Cells and Potent Biofilm Killers of Gram-Positive Pathogens.” ChemBioChem 2017, 18, 352-357. Front Cover Art Selection
  • Paciaroni, N. G.; Ratnayake, R.; Matthews, J. H.; Norwood IV, V. M.; Arnold, A. C.; Dang, L. H.; Luesch, H.; Huigens III, R. W. “A Tryptoline Ring Distortion Strategy Leads to Complex and Diverse Biologically Active Molecules from the Indole Alkaloid Yohimbine.” Chem. Eur. J. 2017, 23, 4327-4335. Cover Art Selection
  • Abouelhassan, Y.; Yang, Q.; Nguyen, M. T.; Rolfe, M.; Yousaf, H. Schultz, G. S.; Huigens III, R. W. “Nitroxoline: A Broad-Spectrum Persister Cell- and Biofilm-Eradicating Agent Against Pathogenic Bacteria.” Int. J. Antimicrob. Agents 2017, 49, 247-251.
  • Garrison, A. T.; Huigens III, R. W. “Eradication of Bacterial Biofilms with Natural Products and Their Inspired Analogues that Operate Through Unique Mechanisms.” Curr. Top. Med. Chem., 2017, 17, 1954-1964. Invited Review for Thematic Issue: “Recent Advances in Anti-biofilm Strategies.”
  • Garrison, A. T.; Abouelhassan, Y.; Yang, H.; Yousaf, H. H.; Nguyen, T.; Huigens III, R. W. “Microwave-Enhanced Friedländer Synthesis for the Rapid Assembly of Halogenated Quinolines with Antibacterial and Biofilm Eradication Activities against Drug Resistant and Tolerant Bacteria.” Med. Chem. Commun. 2017, 8, 720-724. Hot Article; Invited for Themed Issue: “New Talent: Americas”
  • Zuo R.; Garrison A.T.; Basak A.; Zhang P.; Huigens III, R. W.; Ding Y. “In vitro antifungal and antibiofilm activities of halogenated quinoline analogues against Candida albicans and Cryptococcus neoformans.” Int. J. Antimicrob. Agents 2016, 48, 208-211.
  • Basak, A.; Abouelhassan, Y.; Norwood IV, V. M.; Bai, F.; Nguyen, M.; Jin, S.; Huigens III, R. W. “Synthetically Tuning the 2-Position of Halogenated Quinolines: Optimizing Antibacterial and Biofilm Eradication Activities via Alkylation and Reductive Amination Pathways.” Chem. Eur. J. 2016, 22, 9181-9189. Hot Paper, Cover Art Selection, Highlighted in Angew. Chemie. Int. Ed.
  • Garrison, A. T.; Abouelhassan, Y.; Norwood IV, V. M.; Kallifidas, D.; Bai, F.; Nguyen, M.; Rolfe, M. Burch, G. M., Jin, S., Luesch, H.; Huigens III, R. W. “Structure-Activity Relationships of a Diverse Class of Halogenated Phenazines that Targets Persistent, Antibiotic-Tolerant Bacterial Biofilms and Mycobacterium tuberculosis.” J. Med. Chem. 2016, 59, 3808-3825.
  • Paciaroni, N. G.; Borrero, N. V.; Rocca, J. R., Huigens III, R. W. “Rapid Synthesis of Phenazine-1-Carboxyilc Acid Derived Small Molecules from Diverse Anilines: Privileged Structures for Discovery.” Research & Reviews: Journal of Medicinal & Organic Chemistry, 2015, 2, 67-76.
  • Garrison, A. T.; Abouelhassan, Y.; Kallifidas, D.; Bai, F.; Ukhanova, M.; Mai, V.; Jin, S.; Luesch, H.; Huigens III, R. W. “Halogenated Phenazines that Potently Eradicate Biofilms, MRSA Persister Cells in Non-Biofilm Cultures and Mycobacterium tuberculosis.” Angew. Chemie Int. Ed., 2015, 54, 14819-14823.
  • Basak, A.; Abouelhassan, Y.; Huigens III, R. W. “Halogenated Quinolines Discovered Through Reductive Amination with Potent Eradication Activities against MRSA, MRSE and VRE Biofilms.” Org. Biomol. Chem., 2015, 13, 10290-10294. 2015 Hot Articles in Organic and Biomolecular Chemistry
  • Abouelhassan, Y.; Garrison, A. T.; Bai, F.; Norwood IV, V. M.; Nguyen, M.; Jin, S.; Huigens III, R. W. “A Phytochemical-Halogenated Quinoline Combination Therapy Strategy for the Treatment of Pathogenic Bacteria” ChemMedChem, 2015, 10, 1157-1162.
  • Garrison, A. T.; Bai, F.; Abouelhassan, Y.; Paciaroni, N. G.; Jin, S.; Huigens III, R.W. “Bromophenazine Derivatives with Potent Inhibition, Dispersion and Eradication Activities against Staphylococcus aureus Biofilms.” RSC Adv. 2015, 5, 1120-1124.
  •  Abouelhassan, Y.; Garrison, A. T.; Burch, G. M.; Wong, W.; Norwood IV, V. M.; Huigens III, R. W. “Discovery of quinoline small molecules with potent dispersal activity against methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis biofilms using a scaffold hopping strategy.” Bioorg. Med. Chem. Lett., 2014, 24, 5076-5080.
  •  Borrero, N.V.; Bai, F.; Perez, C.; Duong, B.Q.; Rocca, J.R.; Jin, S.; Huigens III, R.W. “Phenazine antibiotic inspired discovery of potent bromophenazine antibacterial agents against Staphylococcus aureus and Staphylococcus epidermidis.” Org. Biomol. Chem. 2014, 12, 881-886.

Select Publications from Graduate and Postdoctoral Studies

  • 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.
  • Rogers, S.A.; Huigens III, R.W.; Cavanagh, J.; Melander, C. “Synergistic effects between conventional antibiotics and 2-aminoimidazole-derived antibiofilm agents.” Antimicrob. Agents & Chemother. 2010, 54, 2112-2118.
  • 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.

Highlighted Publications and Other Press