Christian Melander

George & Winifred Clark Professor

240F Mccourtney Hall
Notre Dame, IN 46556
+1 574-631-9036


Research Areas

  • Biochemistry
  • Organic Chemistry

Research Specialties

  • Medicine
  • Synthesis

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Year Title
2018-Present George & Winifred Clark Professor, University of Notre Dame
2014-2018 Howard J. Schaeffer Distinguished Professor of Chemistry, North Carolina State University
2013-2018 Professor, North Carolina State University
2010-2013 Associate Professor, North Carolina State University
2004-2010 Assistant Professor, North Carolina State University
2002-2004 Research Associate, The Scripps Research Institute
1998-2001 Postdoctoral Scholar, The California Institute of Technology
1998 Ph.D. in Chemistry, Columbia University
1998 M.Phil. in Chemistry, Columbia University
1995 M.A. in Chemistry, Columbia University
1994 B.S. in Chemistry, University of California - Davis

Selected Awards

2014-2018   North Carolina State University Faculty Scholar

2012   NCSU Entrepreneur of the Year

2012   Industrial Innovator of the Year, Southeastern Region, ACS

2009   Sigma Xi Faculty Research Award

Research Interests

The Melander lab is interested broadly in applying the principles of synthetic organic chemistry and microbiology to deliver novel molecules that address problems associated with failure in antibiotic therapy for the treatment of bacterial infections. Specifically, we are interested in developing novel approaches to combat biofilm-based infections that typically give rise to chronic infections (such as those found in Cystic Fibrosis patients, indwelling medical devices, and diabetic ulcers), as well as acute bacterial infections caused by multi-drug resistant pathogens.

Bacterial Biofilms

A biofilm is defined as a surface attached community of bacteria encased in an extracellular matrix. Biofilms are typically 100-1000-fold more resistant to antibiotics and are recalcitrant to clearance by the host immune response. To address this problem, we are investigating the effects that simple structural motifs found embedded in complex marine natural products have upon biofilm development and maintenance. We have demonstrated that simple derivatives of the natural products bromageliferin and oroidin will inhibit and disperse biofilms from pathogenic bacteria as well as fungi and mixed species biofilms. We have also established that our 2-aminoimidazole-derived anti-biofilm agents are non-toxic to red blood cells, mammalian cell lines, and model organisms. The mechanistic basis by which these compounds inhibit and disperse biofilms, as well as the effect these compounds have in vivo are being pursued.

Multi-drug Resistant Bacteria

The rise of multi-drug resistant pathogens is threatening the vast medical advancements made possible by antibiotics over the last 70+ years. Surgery, premature infant care, cancer chemotherapy, care of the critically ill, and transplantation medicine to name a few fields are feasible only with the existence of effective antibiotic therapy. To address this issue, the Melander lab is currently pursing two distinct yet complementary avenues. The first focuses on new chemical matter that give rise to narrow spectrum antibiotic profiles (both small molecules and nanoparticles) that are potentially less damaging to commensal flora and less susceptible to resistance evolution. The second avenue relies upon an adjuvant approach, in which a small molecule that targets resistance mechanisms is paired with currently approved antibiotics. This latter approach is underpinned by the discovery that a certain sub-set of our 2-aminoimidazole library is able to render multi-drug resistant bacterial strains susceptible to various classes of conventional antibiotics. We are currently probing the mechanistic basis of this activity, augmenting activity through analogue synthesis, and exploring the in vivo potential of these compounds in animal models of infection.

Selected Publications

  • Jenul, C.; Keim, K. C.; Jens, J. N.; Zeiler, M. J.; Schilcher, K.; Schurr, M. J.; Melander, C.; Phelan, V. V. and Horswill, A. R. "Pyochelin Biotransformation by Staphylococcus Aureus Shapes Bacterial Competition with Pseudomonas Aeruginosa in Polymicrobial Infections" 2023 Cell Reports, 42 (6), 112540. DOI: 10.1016/j.celrep.2023.112540.
  • Harper, E. I.; Siroky, M. D.; Hilliard, T. S.; Dominique, G. M.; Hammond, C.; Liu, Y. Y.; Yang, J.; Hubble, V. B.; Walsh, D. J.; Melander, R. J.; Melander, C.; Ravosa, M. J. and Stack, M. S. "Advanced Glycation End Products as a Potential Target for Restructuring the Ovarian Cancer Microenvironment: A Pilot Study" 2023 International Journal of Molecular Sciences, 24 (12), 9804. DOI: 10.3390/ijms24129804.
  • Liu, C.; Zhang, H.; Peng, X.; Blackledge, M. S.; Furlani, R. E.; Li, H. T.; Su, Z. M.; Melander, R. J.; Melander, C.; Michalek, S. and Wu, H. "Small Molecule Attenuates Bacterial Virulence by Targeting Conserved Response Regulator" 2023 mBio, 14 (3), e00137-23. DOI: 10.1128/mbio.00137-23.
  • Marrujo, S. A.; Hubble, V. B.; Yang, J. D.; Wang, M.; Nemeth, A. M.; Barlock, S. L.; Juarez, D.; Smith, R. D.; Melander, R. J.; Ernst, R. K.; Chang, M. Y. and Melander, C. "Dimeric 2-Aminoimidazoles are Highly Active Adjuvants for Gram-Positive Selective Antibiotics Against Acinetobacter Baumannii" 2023 European Journal of Medicinal Chemistry, 253, 115329. DOI: 10.1016/j.ejmech.2023.115329.
  • Weig, A. W.; O'Conner, P. M.; Kwiecinski, J. M.; Marciano, O. M.; Nunag, A.; Gutierrez, A. T.; Melander, R. J.; Horswill, A. R. and Melander, C. "A Structure Activity Relationship Study of 3,4'-Dimethoxyflavone for ArlRS Inhibition in Staphylococcus Aureus" 2023 Organic & Biomolecular Chemistry, 21 (16), pp.3373-3380. DOI: 10.1039/d3ob00123g.
  • Onyedibe, K. I.; Nemeth, A. M.; Dayal, N.; Smith, R. D.; Lamptey, J.; Ernst, R. K.; Melander, R. J.; Melander, C. and Sintim, H. O. "Re-Sensitization of Multidrug-Resistant and Colistin-Resistant Gram- Negative Bacteria to Colistin by Povarov/Doebner-Derived Compounds" 2023 ACS Infectious Diseases, 9 (2), pp.283-295. DOI: 10.1021/acsinfecdis.2c00417.