Shaun W. Lee Monahan Family Associate Professor of Rare and Neglected Diseases

Research Interests:

It is our primary research goal to gain a better understanding of the mechanisms behind bacteriocin production and its role in influencing microbial dynamics and host pathogenesis. Bacteriocins are a large class of ribosomally synthesized peptides produced by bacteria that encompass an enormous range of structure and function. It has been estimated that all bacteria and Archaea produce at least one, if not multiple bacteriocin-like peptides, that have diverse activities ranging from antimicrobial, anti-viral, anti-parasitic compounds, to host virulence factors, to bacterial signaling molecules that mediate polymicrobial dynamics and multicellular behaviors such as biofilm formation.  In particular, commensal members of host microbiomes have been identified as a rich source of bacteriocins, and their roles in polymicrobial dynamics are yet to be fully elucidated.  Currently, our major research efforts are focused on two main research goals: 1. Discovery and design of novel bacteriocin candidates for use in therapeutics, and 2. Mechanistic studies on bacteriocins produced by pathogenic and commensal microorganisms in the context of host disease and immunity. Efforts in our laboratory involve important multidisciplinary avenues – chemical approaches for structural identification of bacteriocins, design and screening methods to identify active antibiotic candidates, as well as molecular and microbiology-based approaches to better understand how microorganisms biosynthesize and utilize these bacteriocins.

Biography:

• Monahan Family Associate Professor, University of Notre Dame, IN
• Assistant Professor, University of Notre Dame, IN
• Postdoctoral Fellow, University of California, San Diego, CA
• Ph.D., Oregon Health and Science University, Portland, OR
• B.A., University of California Berkeley, CA

Recent Papers:

• Fields FR, Manzo G, Hind CK, Janardhanan J, Foik IP, Carmo Silva PD, Balsara RD, Clifford M, Vu HM, Ross JN, Kalwajtys VR, Gonzalez AJ, Bui TT, Ploplis VA, Castellino FJ, Siryaporn A, Chang M, Sutton JM, Mason AJ, Lee S. Synthetic Antimicrobial Peptide Tuning Permits Membrane Disruption and Interpeptide Synergy. ACS Pharmacol Transl Sci. 2020 Jun 12;3(3):418-424. doi: 10.1021/acsptsci.0c00001. *Featured on Cover.
• Carothers KE, Liang Z, Mayfield J, Donahue DL, Lee M, Boggess B, Ploplis VA, Castellino FJ, Lee SW. The Streptococcal Protease SpeB Antagonizes the Biofilms of the Human Pathogen Staphylococcus aureus USA300 through Cleavage of the Staphylococcal SdrC Protein. J Bacteriol. 2020 May 11;202(11). doi: 10.1128/JB.00008-20. *Featured on Cover.
• Fields FR, Freed SD, Carothers KE, Nafiz Hamid MD, Hammers DE, Ross JN, Kalwajtys VR, Gonzalez AJ, Hildreth AD, Friedberg I, Lee SW. Novel antimicrobial peptide discovery using machine learning and biophysical selection of minimal bacteriocin domains. Drug Dev Res. 2019;1–9. https://doi.org/10.1002/ ddr.21601. *Featured on Cover.
• Flaherty RA, Donahue DL, Carothers KE, Ross JN, Ploplis VA, Castellino FJ, Lee SW. Neutralization of Streptolysin S-Dependent and Independent Inflammatory Cytokine IL-1β Activity Reduces Pathology During Early Group A Streptococcal Skin Infection. Frontiers in cellular and infection microbiology. 2018; 8:211.
• Fields FR, Carothers KE, Balsara, RD, Ploplis, VA, Castellino, FJ, and Lee, S.W. Rational design of syn-safencin, a novel linear antimicrobial peptide derived from the circular bacteriocins safencin AS-48. 2018. J Antibiotics 71, 592-600.
• Higashi DL, Biais N, Donahue DL, Mayfield JA, Tessier C, Rodriguez K, Ashfeld B, Luchetti J, Ploplis VA, Castellino FJ, Lee, S.W. Activation of band 3 mediates group A Streptococcus streptolysin S-based beta-haemolysis. Nature Microbiology. 2016. DOI: 10.1038. NMICROBIOL2015.4. *Featured on Cover, Nature Microbiology, Feb 2016.
• Flaherty, R., Freed, S., Lee, S.W. The wide world of Bacteriocins: ribosomally encoded bacterial peptides. 2014. PLOS Pathogens 10(7): e1004221.