Robert W Huigens

Robert W Huigens, Ph.D.

Associate Professor And Graduate Coordinator

Department: Medicinal Chemistry
Business Phone: (352) 273-7718
Business Email: rwhuigens@ufl.edu

About Robert W Huigens

Robert Huigens received his bachelors in Biology from the University of North Carolina at Greensboro (2003) and Ph.D. in Chemistry at North Carolina State University (2009). Dr. Huigens then became an American Cancer Society postdoctoral fellow in Professor Paul Hergenrother’s lab at the University of Illinois at Urbana-Champaign. In 2013, Dr. Huigens began his independent career as an assistant professor at the University of Florida in the Medicinal Chemistry Department and was promoted to associate professor with tenure in 2020. Professor Huigens directs an energetic and collaborative research lab inspired by natural products and utilizes a combination of organic synthesis, medicinal chemistry, chemical biology, microbiology and molecular biology to discover new compounds to treat disease and explore biological processes.

Research Profile

The Huigens lab is on a mission to discover new molecules that can treat human disease and study important biological processes. The majority of our work involves chemical synthesis; however, we have a productive microbiology team in our lab developing new assays and studying biofilms using RNA-seq technology. In addition, we are always excited to work with others motivated by drug discovery and chemical biology! Students and postdocs in our group receive training at the interface of chemistry and biology using a combination of synthetic organic chemistry (including complex molecule synthesis), medicinal chemistry and microbiology approaches.

The research in Dr. Huigens’ lab has been primarily funded by the National Institutes of Health (R-35; Maximizing Investigators’ Research Award, National Institute of General Medical Sciences), the American Cancer Society (Research Scholar Grant) and the University of Florida (start-up funds, multiple seed fund awards). In addition, the Huigens lab has also been involved in collaborative projects supported by the National Institutes of Health (NCI) and the Muscular Dystrophy Association, Inc.

In addition, Dr. Huigens’ research has been recognized through multiple Young Investigator Awards from the American Chemical Society, including: (1) Division of Medicinal Chemistry (in recognition for the discovery & development halogenated phenazine biofilm-eradicating agents, 2015), and (2) Division of Organic Chemistry (utilizing indole alkaloids as starting points for ring distortion synthesis and the identification of re-engineered derivatives with activities relevant to cancer, malaria and opioid addiction therapies, 2019). Dr. Huigens was also the recipient of a young investigator award from the Center for Biofilm Engineering (Montana State University) for the group’s medicinal chemistry efforts regarding novel bacterial biofilm-eradicating agents.

Publications

2021
Evolution of Resistance to Phenazine Antibiotics in Staphylococcus aureus and Its Role During Coinfection with Pseudomonas aeruginosa.
ACS infectious diseases. 7(3):636-649 [DOI] 10.1021/acsinfecdis.0c00837. [PMID] 33650853.
2021
Targeting bacterial biofilms with persister-killing agents.
Future medicinal chemistry. 13(3):225-228 [DOI] 10.4155/fmc-2020-0314. [PMID] 33225755.
2020
Efficacy data of halogenated phenazine and quinoline agents and an NH125 analogue to veterinary mycoplasmas.
BMC veterinary research. 16(1) [DOI] 10.1186/s12917-020-02324-4. [PMID] 32252763.
2020
Instructive Advances in Chemical Microbiology Inspired by Nature’s Diverse Inventory of Molecules.
ACS infectious diseases. 6(4):541-562 [DOI] 10.1021/acsinfecdis.9b00413. [PMID] 31842540.
2020
Preventing Morphine-Seeking Behavior through the Re-Engineering of Vincamine’s Biological Activity.
Journal of medicinal chemistry. 63(10):5119-5138 [DOI] 10.1021/acs.jmedchem.9b01924. [PMID] 31913038.
2020
Progress towards a stable cephalosporin-halogenated phenazine conjugate for antibacterial prodrug applications.
Bioorganic & medicinal chemistry letters. 30(22) [DOI] 10.1016/j.bmcl.2020.127515. [PMID] 32860978.
2020
Re-Engineering of Yohimbine’s Biological Activity through Ring Distortion: Identification and Structure-Activity Relationships of a New Class of Antiplasmodial Agents.
ACS infectious diseases. 6(2):159-167 [DOI] 10.1021/acsinfecdis.9b00380. [PMID] 31913597.
2020
Yohimbine as a Starting Point to Access Diverse Natural Product-Like Agents with Re-programmed Activities against Cancer-Relevant GPCR Targets.
Bioorganic & medicinal chemistry. 28(14) [DOI] 10.1016/j.bmc.2020.115546. [PMID] 32616180.
2019
Combination Treatment of Erythromycin and Furamidine Provides Additive and Synergistic Rescue of Mis-Splicing in Myotonic Dystrophy Type 1 Models.
ACS pharmacology & translational science. 2(4):247-263 [DOI] 10.1021/acsptsci.9b00020. [PMID] 31485578.
2019
Harnessing the Chemistry of the Indole Heterocycle to Drive Discoveries in Biology and Medicine.
Chembiochem : a European journal of chemical biology. 20(18):2273-2297 [DOI] 10.1002/cbic.201800768. [PMID] 30609199.
2019
Phenazine Antibiotic-Inspired Discovery of Bacterial Biofilm-Eradicating Agents.
Chembiochem : a European journal of chemical biology. 20(23):2885-2902 [DOI] 10.1002/cbic.201900116. [PMID] 30811834.
2019
Recent Progress in Natural-Product-Inspired Programs Aimed To Address Antibiotic Resistance and Tolerance.
Journal of medicinal chemistry. 62(17):7618-7642 [DOI] 10.1021/acs.jmedchem.9b00370. [PMID] 30951303.
2019
Turning the Tide against Antibiotic Resistance by Evaluating Novel, Halogenated Phenazine, Quinoline, and NH125 Compounds against Ureaplasma Species Clinical Isolates and Mycoplasma Type Strains.
Antimicrobial agents and chemotherapy. 63(3) [DOI] 10.1128/AAC.02265-18. [PMID] 30642935.
2018
An Efficient Buchwald-Hartwig/Reductive Cyclization for the Scaffold Diversification of Halogenated Phenazines: Potent Antibacterial Targeting, Biofilm Eradication, and Prodrug Exploration.
Journal of medicinal chemistry. 61(9):3962-3983 [DOI] 10.1021/acs.jmedchem.7b01903. [PMID] 29638121.
2018
Halogenated quinolines bearing polar functionality at the 2-position: Identification of new antibacterial agents with enhanced activity against Staphylococcus epidermidis.
European journal of medicinal chemistry. 155:705-713 [DOI] 10.1016/j.ejmech.2018.06.045. [PMID] 29936357.
2018
The Path to New Halogenated Quinolines With Enhanced Activities Against Staphylococcus epidermidis.
Microbiology insights. 11 [DOI] 10.1177/1178636118808532. [PMID] 30397386.
2018
Transcript Profiling of MRSA Biofilms Treated with a Halogenated Phenazine Eradicating Agent: A Platform for Defining Cellular Targets and Pathways Critical to Biofilm Survival.
Angewandte Chemie (International ed. in English). 57(47):15523-15528 [DOI] 10.1002/anie.201809785. [PMID] 30230671.
2017
A Highly Potent Class of Halogenated Phenazine Antibacterial and Biofilm-Eradicating Agents Accessed Through a Modular Wohl-Aue Synthesis.
Scientific reports. 7(1) [DOI] 10.1038/s41598-017-01045-3. [PMID] 28515440.
2017
A Tryptoline Ring-Distortion Strategy Leads to Complex and Diverse Biologically Active Molecules from the Indole Alkaloid Yohimbine.
Chemistry (Weinheim an der Bergstrasse, Germany). 23(18):4327-4335 [DOI] 10.1002/chem.201604795. [PMID] 27900785.
2017
Antimicrobial peptide-inspired NH125 analogues: bacterial and fungal biofilm-eradicating agents and rapid killers of MRSA persisters.
Organic & biomolecular chemistry. 15(26):5503-5512 [DOI] 10.1039/c7ob01028a. [PMID] 28534905.
2017
Identification of N-Arylated NH125 Analogues as Rapid Eradicating Agents against MRSA Persister Cells and Potent Biofilm Killers of Gram-Positive Pathogens.
Chembiochem : a European journal of chemical biology. 18(4):352-357 [DOI] 10.1002/cbic.201600622. [PMID] 27925693.
2017
Microwave-enhanced Friedländer synthesis for the rapid assembly of halogenated quinolines with antibacterial and biofilm eradication activities against drug resistant and tolerant bacteria.
MedChemComm. 8(4):720-724 [DOI] 10.1039/c6md00381h. [PMID] 30108790.
2017
Nitroxoline: a broad-spectrum biofilm-eradicating agent against pathogenic bacteria.
International journal of antimicrobial agents. 49(2):247-251 [DOI] 10.1016/j.ijantimicag.2016.10.017. [PMID] 28110918.
2016
In vitro antifungal and antibiofilm activities of halogenated quinoline analogues against Candida albicans and Cryptococcus neoformans.
International journal of antimicrobial agents. 48(2):208-11 [DOI] 10.1016/j.ijantimicag.2016.04.019. [PMID] 27256584.
2016
Structure-Activity Relationships of a Diverse Class of Halogenated Phenazines That Targets Persistent, Antibiotic-Tolerant Bacterial Biofilms and Mycobacterium tuberculosis.
Journal of medicinal chemistry. 59(8):3808-25 [DOI] 10.1021/acs.jmedchem.5b02004. [PMID] 27018907.
2016
Synthetically Tuning the 2-Position of Halogenated Quinolines: Optimizing Antibacterial and Biofilm Eradication Activities via Alkylation and Reductive Amination Pathways.
Chemistry (Weinheim an der Bergstrasse, Germany). 22(27):9181-9 [DOI] 10.1002/chem.201600926. [PMID] 27245927.
2015
A Phytochemical-Halogenated Quinoline Combination Therapy Strategy for the Treatment of Pathogenic Bacteria.
ChemMedChem. 10(7):1157-62 [DOI] 10.1002/cmdc.201500179. [PMID] 25982664.
2015
Halogenated Phenazines that Potently Eradicate Biofilms, MRSA Persister Cells in Non-Biofilm Cultures, and Mycobacterium tuberculosis.
Angewandte Chemie (International ed. in English). 54(49):14819-23 [DOI] 10.1002/anie.201508155. [PMID] 26480852.
2015
Halogenated quinolines discovered through reductive amination with potent eradication activities against MRSA, MRSE and VRE biofilms.
Organic & biomolecular chemistry. 13(41):10290-4 [DOI] 10.1039/c5ob01883h. [PMID] 26414088.
2014
Discovery of quinoline small molecules with potent dispersal activity against methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis biofilms using a scaffold hopping strategy.
Bioorganic & medicinal chemistry letters. 24(21):5076-80 [DOI] 10.1016/j.bmcl.2014.09.009. [PMID] 25264073.
2014
Phenazine antibiotic inspired discovery of potent bromophenazine antibacterial agents against Staphylococcus aureus and Staphylococcus epidermidis.
Organic & biomolecular chemistry. 12(6):881-6 [DOI] 10.1039/c3ob42416b. [PMID] 24389824.
2013
A ring-distortion strategy to construct stereochemically complex and structurally diverse compounds from natural products.
Nature chemistry. 5(3):195-202 [DOI] 10.1038/nchem.1549. [PMID] 23422561.
2013
Dual targeting of the Warburg effect with a glucose-conjugated lactate dehydrogenase inhibitor.
Chembiochem : a European journal of chemical biology. 14(17):2263-7 [DOI] 10.1002/cbic.201300562. [PMID] 24174263.
2012
Foliar-Applied Small Molecule that Suppresses Biofilm Formation and Enhances Control of Copper-Resistant Xanthomonas euvesicatoria on Pepper.
Plant disease. 96(11):1638-1644 [DOI] 10.1094/PDIS-02-12-0190-RE. [PMID] 30727459.
2011
Synthesis and biological activity of 2-aminoimidazole triazoles accessed by Suzuki-Miyaura cross-coupling.
Organic & biomolecular chemistry. 9(8):3041-9 [DOI] 10.1039/c0ob00925c. [PMID] 21394327.
2010
Modulating the development of E. coli biofilms with 2-aminoimidazoles.
Bioorganic & medicinal chemistry letters. 20(21):6310-2 [DOI] 10.1016/j.bmcl.2010.08.075. [PMID] 20846860.
2010
Synergistic effects between conventional antibiotics and 2-aminoimidazole-derived antibiofilm agents.
Antimicrobial agents and chemotherapy. 54(5):2112-8 [DOI] 10.1128/AAC.01418-09. [PMID] 20211901.
2010
The chemical synthesis and antibiotic activity of a diverse library of 2-aminobenzimidazole small molecules against MRSA and multidrug-resistant A. baumannii.
Bioorganic & medicinal chemistry. 18(2):663-74 [DOI] 10.1016/j.bmc.2009.12.003. [PMID] 20044260.
2009
A 2-aminobenzimidazole that inhibits and disperses gram-positive biofilms through a zinc-dependent mechanism.
Journal of the American Chemical Society. 131(29):9868-9 [DOI] 10.1021/ja9024676. [PMID] 19621946.
2009
Evaluation of dihydrooroidin as an antifouling additive in marine paint.
International biodeterioration & biodegradation. 63(4):529-532 [PMID] 23874076.
View on: PubMed
2009
Inhibition of Acinetobacter baumannii, Staphylococcus aureus and Pseudomonas aeruginosa biofilm formation with a class of TAGE-triazole conjugates.
Organic & biomolecular chemistry. 7(4):794-802 [DOI] 10.1039/b817926c. [PMID] 19194596.
2008
Control of bacterial biofilms with marine alkaloid derivatives.
Molecular bioSystems. 4(6):614-21 [DOI] 10.1039/b719989a. [PMID] 18493660.
2008
Synthesis and screening of an oroidin library against Pseudomonas aeruginosa biofilms.
Chembiochem : a European journal of chemical biology. 9(8):1267-79 [DOI] 10.1002/cbic.200700774. [PMID] 18431726.
2007
Inhibition of Pseudomonas aeruginosa biofilm formation with Bromoageliferin analogues.
Journal of the American Chemical Society. 129(22):6966-7 [PMID] 17500516.
View on: PubMed

Grants

Mar 2021 ACTIVE
Optimization and mechanistic studies of halogenated phenazines and quinolines as anti-tuberculosis therapeutics
Role: Principal Investigator
Funding: UNIV OF CENTRAL FLORIDA via NATL INST OF HLTH NIAID
Aug 2019 – Jul 2020
Impeding Transcriptions of the Toxic RNAs of Myotonic Dystrophy
Role: Principal Investigator
Funding: STATE UNIV OF NEW YORK RES FOU via MUSCULAR DYSTROPHY ASSO
Sep 2018 – Aug 2019
Impeding Transcriptions of the Toxic RNAs of Myotonic Dystrophy
Role: Principal Investigator
Funding: STATE UNIV OF NEW YORK RES FOU via MUSCULAR DYSTROPHY ASSO
Aug 2018 ACTIVE
Indole Alkaloids and Phenazine Antibiotics: New Platforms for Drug Discovery
Role: Principal Investigator
Funding: NATL INST OF HLTH NIGMS
Jul 2018 ACTIVE
Alkaloid Ring Distortion: A Platform for New Cancer Therapies
Role: Principal Investigator
Funding: AMER CANCER SOC
Sep 2016 – Aug 2017
Rho Chi AFPE Fellowship
Role: Other
Funding: AMER FOU FOR PHARM EDU
Jun 2016 – May 2019
Nitroxoline Small Molecules as Cures for Persistent Bacterial Infections
Role: Principal Investigator
Funding: UF DSR OPPORTUNITY FUND
Jan 2016 ACTIVE
Studies on thymidylate synthase as a tumor-promoting oncogene for development of new allosteric inhibitors for cancer treatment
Role: Project Manager
Funding: NATL INST OF HLTH NCI
Jun 2014 – May 2016
Development of Potent 2,4-Dibromophenazine Antibacterial Antibiofilm Agents
Role: Principal Investigator
Funding: UF DSR OPPORTUNITY FUND

Patents

Published March 2018
Halogenated Quinoline Derivatives at the 2-Position with Potent Antibacterial and Biofilm Eradication Activities
#US-2018-0265475-A1
Published January 2018
Phenazine Derivatives as Antimicrobial Agents
#US-2018-0312473-A1
Issued January 2018
Phenazine Derivatives as Antimicrobial Agents
#9,856,225

Education

American Cancer Society Postdoctoral Fellow
2009-2013 · University of Illinois at Urbana-Champaign
Ph.D.
2009 · North Carolina State University
B.A.
2003 · University of North Carolina at Greensboro

Teaching Profile

Courses Taught
2015,2018-2021
PHA6935 Selected Topics in Pharmacy
2014-2021
PHA7980 Research for Doctoral Dissertation
2015,2018-2020,2020-2021
PHA6971 Research for Master’s Thesis
2014-2021
PHA7979 Advanced Research
2014-2015,2017-2021,2020-2021
PHA6447 Drug Design
2016-2021
PHA5782C Patient Care 2
2014-2018,2020-2021
PHA6910 Supervised Research
2020-2021
PHA7939 Journal Colloquy in Pharmacodynamics
2015-2016,2018-2020,2020
GMS6009 Principles of Drug Action and Therapeutics
2016,2018-2020,2020
PHA6472 Organic Synthesis of Drug Molecules
2017-2019
PHA5784C Pt Care 4: GI and Renal
2015-2018,2020-2021
PHA5439 Prin Med Chem-Pcol I
2018
GMS7980 Research for Doctoral Dissertation
2018
GMS7979 Advanced Research
2018
CHM7979 Advanced Research
2014-2018,2021
PHA6905C Research Procedures in Medicinal Chemistry
2016-2017
PHA5878C Pt Care 3: Cv and Pulm
2015-2016
PHA6934 Seminar in Medicinal Chemistry
2015-2016
PHA5438 Medicinal Chemistry 2
2013-2015
PHA5906 Research in Med Chem
2014
PHA5433 Funda Medicinal Chem
2020-2021
PHA5930 Sem Pharm Research

Contact Details

Phones:
Business:
(352) 273-7718
Emails:
Business:
rwhuigens@ufl.edu

Huigens Lab 2018

Huigens Lab 2015

Huigens Lab 2014