American Cancer Society Postdoctoral Fellow, University of Illinois at Urbana-Champaign, 2009-2013

Ph.D. Organic Chemistry, North Carolina State University, 2004-2009

B.A. Biology, University of North Carolina at Greensboro, 2000-2003

Medicinal Chemistry, Organic Chemistry, Chemical Synthesis, Drug Discovery, Chemical Biology, Infectious Disease, Bacterial Biofilms

• 2024 NIH ad hoc Reviewer; Biochemistry & Biophysics MIRA Panel (10 ZRG1 MBBC-B (55) R)
• 2024 American Cancer Society ad hoc Grant Reviewer (January 2024 & June 2024)
• 2023 American Cancer Society ad hoc Grant Reviewer
• 2023 NC State University Alumni Speaker
• 2021 NIH ad hoc Reviewer; Coccidioidomycosis Collaborative Research Centers
• 2020 NIH ad hoc Reviewer; Combating Antibiotic-Resistant Bacteria Interdisciplinary Research Units (CARBIRU)
• 2019 Young Investigator Award, American Chemical Society (Division of Organic Chemistry)
• 2018-2023 Maximizing Investigators’ Research Award; National Institute of General Medical Sciences
• 2018-2022 American Cancer Society Research Scholar
• 2017 NIH ad hoc Reviewer; Partnerships for Countermeasures Against Select Pathogens: Therapeutics, Immunotherapeutics, and Vaccines Review Panel
• 2017 Teacher of the Year, College of Pharmacy, University of Florida
• 2016 NIH Early Career Reviewer, Anti-Infective Drug Discovery and Mechanism of Resistance (DDR)
• 2015 Young Investigator Award, Center for Biofilm Engineering (Montana State University)
• 2015 Young Investigator Award, American Chemical Society (Division of Medicinal Chemistry)
• 2010-2013 American Cancer Society Postdoctoral Fellow (UIUC)
• 2008-2009 Jimmy V Scholarship/Predoctoral Fellow (NCSU)
• 2007 Sara & Chloe Novak Award for Excellence in Teaching of Organic Chemistry (NCSU)
• 2006-2007 Phi Lambda Upsilon Treasurer (NCSU)
• 2005 Phi Lambda Upsilon Membership (NCSU)
• 2004 Phi Beta Kappa Society Membership
• 2003 Graduated Summa Cum Laude (UNCG)
• 2003 Eberhart Award (UNCG Biology)
• 2003 Student Excellence Award (UNCG Honors College)
• 2003 American Chemical Society Organic Chemistry Award (UNCG Chemistry)
• 2001-2002 Beta Beta Beta Society President (UNCG Biology)
• 2001 Beta Beta Beta Society Membership (UNCG Biology)

The overarching goal of the Huigens lab is to discover and develop new small molecules that can be used to explore or treat significant disease areas. Our interdisciplinary group is actively involved in: (1) developing approaches that enable us to better understand and eradicate surface-attached bacterial biofilms, (2) utilizing readily available indole alkaloids as starting points to rapidly generate complex and diverse compound collections for biological screening in areas of critical importance (e.g., opioid addiction, cancer, inflammation, malaria), and (3) harnessing synthetic medicinal chemistry to optimize various small molecules in targeted disease areas in collaboration with disease experts (i.e., cancer, myotonic dystrophy). Students and postdocs in our group receive rigorous training at the interface of chemistry and biology using a combination of synthetic organic chemistry, medicinal chemistry, chemical biology, and microbiology approaches.

Schultz, D.C.; Chavez-Riveros, A.; Goertzen II, M.G.; Brummel, B.R.; Paes, R.A.; Santos, N.M.; Tenneti, S.; Abboud, K.A.; Rocca, J.R.; Seabra, G.; Li, C.; Chakrabarti, D.; Huigens III, R.R. “Chloroformate-Mediated Ring Cleavage of Indole Alkaloids Leads to Re-engineered Antiplasmodial Agents” Org. Biomol. Chem. 2024. DOI: 10.1039/D4OB00853G (accepted 6-26-2024)

Liu, K.; Xiao, T.; Yang, H.; Chen, M.; Gao, Q.; Brummel, B.R.; Ding, Y.; Huigens III, R.W. “Design, Synthesis and Evaluation of Halogenated Phenazine Antibacterial Prodrugs Targeting Nitroreductase Enzymes for Activation.” RSC Med. Chem. 2023, 14, 1472-1481.

Leas, D.A.; Schultz, D.C.; Huigens III, R.W. “Chemical Reactions of Indole Alkaloids That Enable Rapid Access to New Scaffolds for Discovery.” SynOpen 2023, 7, 165-185.

Xiao, T.; Liu, K.; Gao, Q.; Chen, M.; Kim, Y.S.; Jin, S.; Ding, Y.; Huigens III, R.W. “Design, Synthesis and Evaluation of Carbonate-Linked Halogenated Phenazine-Quinone Prodrugs with Improved Water-Solubility and Potent Antibacterial Profiles.” ACS Infect. Dis. 2023, 9, 899-915.

Liu, K.; Abouelhassan, Y.; Zhang, Y.; Jin, S.; Huigens III, R.W. “Transcript Profiling of Nitroxoline-Treated Biofilms Shows a Rapid Upregulation of Iron Acquisition Gene Clusters.” ACS Infect. Dis. 2022, 8, 1594-1605.

Liu, K.; Brivio, M.; Xiao, T.; Norwood IV, V. M.; Kim, Y. S.; Jin, S.; Papagni, A.*; Vaghi, L.*; Huigens III, R. W.* “Modular Synthetic Routes to Fluorine-Containing Halogenated Phenazine and Acridine Agents that Induce Rapid Iron Starvation in MRSA Biofilms.” ACS Infect. Dis. 2022, 8, 280-295.

Norwood IV, V.M.; Murillo-Solano, C.; Goertzen II, M.G.; Brummel, B.R.; Perry, D.L.; Rocca, J.R.; Chakrabarti, D.*; Huigens III, R.W.* “Ring Distortion of Vincamine Leads to the Identification of Re-Engineered Antiplasmodial Agents.” ACS Omega 2021, 6, 20455-20470.

Yang, H.; Kundra, S.; Chojnacki, M.; Liu, K.; Fuse, M.A.; Abouelhassan, Y.; Kallifidas, D.; Zhang, P.; Huang, G.; Jin, S.; Ding, Y.; Luesch, H.; Rohde, K.H.; Dunman, P.M.; Lemos, J.A.; Huigens III, R.W. “A Modular Synthetic Route Involving N-Aryl-2-Nitrosoaniline Intermediates Leads to a New Series of 3-Substituted Halogenated Phenazine Antibacterial Agents.” J. Med. Chem. 2021, 64, 7275-7295.

Fu, T.; Cai, Z.; Yue, Z.; Yang, H.; Fang, B.; Zhang, X.; Fan, Z.; Pan, X.; Yang, F.; Jin, Y.; Cheng, Z.; Wu, W.; Sun, B.L.; Huigens III, R.W.; Yang, L.; Bai, F. “Evolution of Resistance to Phenazine Antibiotics in Staphylococcus aureus and its Role During Co-infection with Pseudomonas aeruginosa.” ACS Infect. Dis. 2021, 7, 636-649.

Paciaroni, N.G.; Norwood IV, V.M.; Ratnayake, R.; Luesch, H.*; Huigens III, R.W.* “Yohimbine as a Starting Point to Access Diverse Natural Product-Like Agents with Re-programmed Activities against Cancer-Relevant GPCR Targets.” Bioorg. Med. Chem. 2020, 28, 115546.

Norwood IV, V.M.; Brice-Tutt, A.; Eans, S.O.; Stacy, H.; Shi, G.; Ratnayake, R.; Rocca, J. R.; Abboud, K.A.; Li, C.; Luesch, H.; McLaughlin, J. P.; Huigens III, R.W. “Preventing Morphine-Seeking Behavior through the Re engineering of Vincamine’s Biological Activity.” J. Med. Chem. 2020, 63, 5119-5138.

Paciaroni, N.G.; Perry, D.; Norwood IV, V.M.; Murillo-Solano, C.; Collins, J.; Tenneti, S.; Chakrabarti, D.*; Huigens III, R.W.* “Re-engineering of Yohimbine’s Biological Activity through Ring Distortion: Identification and Structure-Activity Relationships of a New Class of Antiplasmodial Agents.” ACS Infect. Dis. 2020, 6, 159-167.

Liu, K.; Huigens III, R.W. “Instructive Advances in Chemical Microbiology Inspired by Nature’s Diverse Inventory of Molecules.” ACS Infect. Dis. 2020, 6, 541-562.

Abouelhassan, Y.; Garrison, A.T.; Yang, H.; Chávez-Riveros, A.; Burch, G.; Huigens III, R.W. “Recent Progress in Natural-Product-Inspired Programs Aimed at Addressing Antibiotic Resistance and Tolerance.” J. Med. Chem. 2019, 62, 7618-7642.

Huigens III, R.W.; Abouelhassan, Y.; Yang, H. “Phenazine Antibiotic-Inspired Discovery of Bacterial Biofilm Eradicating Agents.” ChemBioChem 2019, 20, 2885-2902.

Norwood IV, V.M.; Huigens III, R.W. “Harnessing the Chemistry of the Indole Heterocycle to Drive Discoveries in Biology and Medicine.” ChemBioChem 2019, 20, 2273-2297.

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. 2018, 57, 15523-15528.

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. 2018, 61, 3962-3983.

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.

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.

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.

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.

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. Chem. Int. Ed. 2015, 54, 14819-14823.

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.

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.; Melander, C. “Inhibition of Acinetobacter baumannii, Staphylococcus aureus, and Pseudomonas aeruginosa biofilms with a class of TAGE-triazole conjugates.” Org. Biomol. 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. BioSyst. 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.

We thank the agencies below for providing generous external funding for our present and past research efforts.

• National Institute of General Medical Sciences (PI: 1R35GM153272, 1R35GM128621)
• American Cancer Society (PI: 131947-RSG-18-013-01-CDD)
• National Institute of Dental and Craniofacial Research (Co-I: 1R01DE032555-01A1)
• National Institute of Allergy and Infectious Diseases (Co-I: 1R21AI159191)
• National Cancer Institute (Co-I: 1R01CA188132-01A1)
• Muscular Dystrophy Association, Inc. (Co-I)