Dr. Rachel Hevey Department of Pharmaceutical Sciences Profiles & Affiliations OverviewResearch Publications Publications by Type Projects & Collaborations Academic Activities Academic Reputation & Networking Projects & Collaborations OverviewResearch Publications Publications by Type Projects & Collaborations Academic Activities Academic Reputation & Networking Profiles & Affiliations Projects & Collaborations 3 foundShow per page10 10 20 50 Development of glycan-based antimicrobial therapies Research Project | 3 Project MembersAntimicrobial resistance is reaching a global crisis and the WHO considers it a major health threat. Alternative therapies for infection are urgently needed, therefore we have developed a novel drug class targeting a range of pathogens while retaining natural flora to restore microbiome homeostasis. Novel treatment approach to enable blood group-incompatible transplantations Research Project | 2 Project MembersTransplant shortages have necessitated blood group-incompatible organ/stem cell transplantation. To ease organ deficit and improve patients' lives, we have designed glycopolymers to selectively remove circulating antibodies, reducing dependence on immunosuppresants and associated infection risk. Investigation of a novel target for attenuating bacterial infection Research Project | 2 Project MembersRecent data clearly illustrate the growing threat of infectious pathogens, with nearly 3 million antibiotic-resistant infections recorded annually in the US and 35,000 of these resulting in morbidity. Antibiotic resistance results in failed treatment, prolonged hospital stays, and increases the financial burden placed on the medical system. Therefore, novel approaches to antibiotic use and/or combination therapies are urgently needed. Recent studies have demonstrated a novel role of mucin glycans in attenuating pathogen virulence in several cross-kingdom species, including Pseudomonas aeruginosa , Candida albicans , and Streptococcus mutans . In a P. aeruginosa porcine burn model, glycan treatment significantly reduced pathogen virulence and increased bacterial susceptibility to host immune defense, thereby indirectly reducing infection load. Based on these observations, a therapeutic molecule which targets the same entity as the mucin glycans would be a promising novel approach to treating infection, and should have a reduced risk of developing resistance as it does not directly affect bacterial survival. This approach to treating infections is highly unconventional as it targets virulence gene regulation rather than pathogen survival. Given that mucins contain hundreds of different O-glycan structures and therefore their individual glycans cannot be purified from native sources, we have been developing a synthetic platform to access a library of O-glycans and have used this to establish several lead compounds. As mucin glycans are not commercially available, this puts us in the unique position of being able to probe individual molecular interactions and elucidate the unique roles of individual glycan structures. Based on these initial lead compounds, we aim to design, synthesize, and evaluate a series of glycomimetic ligands to assess their potential as novel therapeutics. If successful, this would afford the first example of therapeutically using mucin-derived glycomimetics to attenuate pathogen virulence in infection. Given the importance of antibiotic-resistance and novel approaches to treating infection, the attenuation of microbial virulence is a promising therapeutic approach as it renders pathogens more susceptible to host immunity. The proposed project will afford a better understanding of mucin-based glycan interactions with pathogens, and early-generation glycomimetics will represent a first class of therapeutic compounds targeting virulence gene suppression. 1 1 OverviewResearch Publications Publications by Type Projects & Collaborations Academic Activities Academic Reputation & Networking
Projects & Collaborations 3 foundShow per page10 10 20 50 Development of glycan-based antimicrobial therapies Research Project | 3 Project MembersAntimicrobial resistance is reaching a global crisis and the WHO considers it a major health threat. Alternative therapies for infection are urgently needed, therefore we have developed a novel drug class targeting a range of pathogens while retaining natural flora to restore microbiome homeostasis. Novel treatment approach to enable blood group-incompatible transplantations Research Project | 2 Project MembersTransplant shortages have necessitated blood group-incompatible organ/stem cell transplantation. To ease organ deficit and improve patients' lives, we have designed glycopolymers to selectively remove circulating antibodies, reducing dependence on immunosuppresants and associated infection risk. Investigation of a novel target for attenuating bacterial infection Research Project | 2 Project MembersRecent data clearly illustrate the growing threat of infectious pathogens, with nearly 3 million antibiotic-resistant infections recorded annually in the US and 35,000 of these resulting in morbidity. Antibiotic resistance results in failed treatment, prolonged hospital stays, and increases the financial burden placed on the medical system. Therefore, novel approaches to antibiotic use and/or combination therapies are urgently needed. Recent studies have demonstrated a novel role of mucin glycans in attenuating pathogen virulence in several cross-kingdom species, including Pseudomonas aeruginosa , Candida albicans , and Streptococcus mutans . In a P. aeruginosa porcine burn model, glycan treatment significantly reduced pathogen virulence and increased bacterial susceptibility to host immune defense, thereby indirectly reducing infection load. Based on these observations, a therapeutic molecule which targets the same entity as the mucin glycans would be a promising novel approach to treating infection, and should have a reduced risk of developing resistance as it does not directly affect bacterial survival. This approach to treating infections is highly unconventional as it targets virulence gene regulation rather than pathogen survival. Given that mucins contain hundreds of different O-glycan structures and therefore their individual glycans cannot be purified from native sources, we have been developing a synthetic platform to access a library of O-glycans and have used this to establish several lead compounds. As mucin glycans are not commercially available, this puts us in the unique position of being able to probe individual molecular interactions and elucidate the unique roles of individual glycan structures. Based on these initial lead compounds, we aim to design, synthesize, and evaluate a series of glycomimetic ligands to assess their potential as novel therapeutics. If successful, this would afford the first example of therapeutically using mucin-derived glycomimetics to attenuate pathogen virulence in infection. Given the importance of antibiotic-resistance and novel approaches to treating infection, the attenuation of microbial virulence is a promising therapeutic approach as it renders pathogens more susceptible to host immunity. The proposed project will afford a better understanding of mucin-based glycan interactions with pathogens, and early-generation glycomimetics will represent a first class of therapeutic compounds targeting virulence gene suppression. 1 1
Development of glycan-based antimicrobial therapies Research Project | 3 Project MembersAntimicrobial resistance is reaching a global crisis and the WHO considers it a major health threat. Alternative therapies for infection are urgently needed, therefore we have developed a novel drug class targeting a range of pathogens while retaining natural flora to restore microbiome homeostasis.
Novel treatment approach to enable blood group-incompatible transplantations Research Project | 2 Project MembersTransplant shortages have necessitated blood group-incompatible organ/stem cell transplantation. To ease organ deficit and improve patients' lives, we have designed glycopolymers to selectively remove circulating antibodies, reducing dependence on immunosuppresants and associated infection risk.
Investigation of a novel target for attenuating bacterial infection Research Project | 2 Project MembersRecent data clearly illustrate the growing threat of infectious pathogens, with nearly 3 million antibiotic-resistant infections recorded annually in the US and 35,000 of these resulting in morbidity. Antibiotic resistance results in failed treatment, prolonged hospital stays, and increases the financial burden placed on the medical system. Therefore, novel approaches to antibiotic use and/or combination therapies are urgently needed. Recent studies have demonstrated a novel role of mucin glycans in attenuating pathogen virulence in several cross-kingdom species, including Pseudomonas aeruginosa , Candida albicans , and Streptococcus mutans . In a P. aeruginosa porcine burn model, glycan treatment significantly reduced pathogen virulence and increased bacterial susceptibility to host immune defense, thereby indirectly reducing infection load. Based on these observations, a therapeutic molecule which targets the same entity as the mucin glycans would be a promising novel approach to treating infection, and should have a reduced risk of developing resistance as it does not directly affect bacterial survival. This approach to treating infections is highly unconventional as it targets virulence gene regulation rather than pathogen survival. Given that mucins contain hundreds of different O-glycan structures and therefore their individual glycans cannot be purified from native sources, we have been developing a synthetic platform to access a library of O-glycans and have used this to establish several lead compounds. As mucin glycans are not commercially available, this puts us in the unique position of being able to probe individual molecular interactions and elucidate the unique roles of individual glycan structures. Based on these initial lead compounds, we aim to design, synthesize, and evaluate a series of glycomimetic ligands to assess their potential as novel therapeutics. If successful, this would afford the first example of therapeutically using mucin-derived glycomimetics to attenuate pathogen virulence in infection. Given the importance of antibiotic-resistance and novel approaches to treating infection, the attenuation of microbial virulence is a promising therapeutic approach as it renders pathogens more susceptible to host immunity. The proposed project will afford a better understanding of mucin-based glycan interactions with pathogens, and early-generation glycomimetics will represent a first class of therapeutic compounds targeting virulence gene suppression.
