B.S. Ithaca College, 2003
Ph.D. Purdue University, 2009
NIH Postdoctoral Fellow, University of Pennsylvania, 2009-2011
The Pires lab uses synthetic chemistry as a platform to construct cell wall analogs that metabolically label live bacteria and mimic key aspects of cell wall architecture. Through this work, the interrogation of cell wall remodeling and processing in pathogenic bacteria will guide the design of next-generation antibiotics that circumvent resistance mechanisms. Moreover, we are working to establish the fundamental framework of a non-traditional antibiotic therapy based on the specific recruitment of components of the immune cells to target the destruction of pathogenic bacteria.
Every year in the United States, over two million people are afflicted with bacterial infections resistant to FDA-approved antibiotics. In order to counter the rapid rise in drug-resistance in bacteria, new drug targets and diagnostic tests are urgently needed. The bacterial cell wall has proven to be a rich source of antibiotic drug discovery. However, there are fundamental aspects of bacterial cell wall assembly and its interaction with the host organism that are yet to be fully elucidated.
Bacterial Cell Wall Probes – Chemical Microbiology
The Pires laboratory will leverage the laboratory expertise in building synthetic bacterial cell wall mimics to reveal key aspects of peptidoglycan recognition and cell wall remodeling. We anticipate that interrogation of cell wall remodeling and processing in pathogenic bacteria will guide the design of next-generation antibiotics that circumvent resistance mechanisms. Our work has yielded synthetic cell wall mimics that reveal how bacterial cell wall building blocks regulate surface remodeling and biosynthesis.
Synthetic Immunotherapeutics Against Bacterial Pathogens
We are developing unique antimicrobial therapeutic strategies based on a specific modulation of the immune response to combat bacterial infections. We have established novel methods to re-engage components of the immune system to induce a targeted immunological response to the site of infection. The goal is to assemble and evaluate agents that induce the recruitment of antibodies or the direct engagement with human immune cells. This new class of agents will constitute a way of mobilizing the immune system to target poorly immunogenic bacterial pathogens.
Apostolos AJ, Kelly J, Ongwae G., Pires M."Structure Activity Relationship of the Murein Peptide in Sortase A mediated Ligation from Staphylococcus aureus" (2021), in preparation.
Ferraro NJ, Pires M. "Transposon Screen of Surface Accessibility in Staphylococcus aureus" (2021), submitted.
Apostolos AJ, Yehiya TK, Silva JR, Lameira J, Alves MC, Siegrist MS, Pires M. "Metabolic Processing of Selenium-based Bioisostere of meso-diaminopimelic Acid in Live Bacteria" (2021), submitted.
Ongwae G, Chordia M, Cawley JL, Dalesandro BE, Wittenberg NJ, Pires M. "Targeting of Pseudomonas aeruginosa Cell Surface via GP12, an Escherichia coli Specific Bacteriophage" Scientific Reports (2021), accepted.
Apostolos AJ, Pires M. "Impact of Crossbridge Structure on Peptidoglycan Crosslinking: A Synthetic Stem Peptide Approach" Methods in Enzymology (2021), accepted.
Sikorski EL, Wehr J, Ferraro NJ, Pires M, Thévenin D. "Selective Display of a Chemoattractant Agonist on Cancer Cells Activates the Formyl Peptide Receptor 1 on Immune Cells" ChemBioChem (2021), accepted.
Ferraro NJ, Kim S, Im W, Pires M. "Systematic Assessment of Accessibility to the Surface of Staphylococcus aureus." ACS Chemical Biology (2021) 16, 2527-2536.
Apostolos AJ, Ferraro NJ, Dalesandro BE, Pires M. "SaccuFlow: A High-Throughput Analysis Platform to Investigate Bacterial Cell Wall Interactions." ACS Infectious Diseases (2021) 7, 2483-2491.
Wehr J, Sikorski EL, Bloch E, Feigman MS, Ferraro NJ, Baybutt TR, Snook AE, Pires M, Thévenin D. "pH-Dependent Grafting of Cancer Cells with Antigenic Epitopes Promotes Selective Antibody-Mediated Cytotoxicity. Journal of Medicinal Chemistry (2020), 63, 3713-3722.
Dalesandro BE, Pires M. “Induction of Induction of Endogenous Antibody Recruitment to the Surface of the Pathogen Enterococcus faecium.” ACS Infectious Diseases (2020), 7, 1116-1125.
Apostolos AJ, Nelson J, Pires M. “Facile Synthesis and Metabolic Incorporation of m-DAP Bioisosteres Into Cell Walls of Live Bacteria.” ACS Chemical Biology (2020), 15, 2966-2975.
Apostolos AJ, Pidgeon SE, Pires M. “Remodeling of Cross-bridges Controls Peptidoglycan Cross-linking Levels in Bacterial Cell Walls.” ACS Chemical Biology (2020), 15,1261-1267.
Ongwae GM, Morrison KR, Allen RA, Kim S, Im W, Wuest WM, Pires M. “Broadening Activity of Polymyxin by Quaternary Ammonium Grafting.” ACS Infectious Diseases (2020) 6, 1427-1435.
Wehr J, Sikorski EL, Bloch E, Feigman MS, Ferraro NJ, Baybutt TR, Snook AE, Pires M, Thévenin D. “pH-Dependent Grafting of Cancer Cells With Antigenic Epitopes Promotes Selective Antibody-Mediated Cytotoxicity.” Journal of Medicinal Chemistry (2020) 63, 3713-3722.
Wang L, Jakob S, Wang H, Apostolos A, Pires M, Xu XG. “Generalized Heterodyne Configurations for Photoinduced Force Microscopy.” Analytical Chemistry (2019) 91, 13251-13259.
Pidgeon S, Apostolos A, Nelson J, Shaku M, Rimal B, Islam M, Crick C, Kim J, Pavelka S, Kana D, Pires M. “L,D-Transpeptidase Specific Probe Reveals Spatial Activity of Peptidoglycan Cross-Linking.” ACS Chemical Biology (2019) 14, 2185-2196.