Yongrong Zhang Laboratory
Our main research interests are understanding the mechanisms of C. difficile virulent factors and seeking therapeutic targets to treat CDI. CDI is prevalent in the western world. In United States, it costs millions of dollars each year to combat with this superbug. The challenge in controlling C. difficile is the extensive resistance to antibiotics. Effective non-antibiotic treatments are urgently needed. Understanding the mechanism of its virulent factor is extremely helpful to develop effective interventions against the disease. Previously, our laboratory has identified several domain function related molecular mechanisms of the exotoxins: 1) The glucosyltransferase activity of the toxins is critical for the pathogenesis of C. difficile infection; 2) A 97-amino-acid fragment located in the translocation domain contributes to deliver the glucosyltransferase domain of TcdB into cytoplasma; 3) The combined repetitive oligopeptides (CROPs) of TcdA blocks its autoprocessing; 4) Autoprotease domain mediated autocleavage acts as a dual switch to regulate the cytotoxicity and proinflammatory activity of C. difficile glucosylating toxins. Based on the findings, several therapeutic antibodies have been identified from immuned nanobody library and shown superior efficacy in various animal models.
Investigate the pharmacokinetics of engineered probiotic yeast carrying various immuno-therapeutic compounds in gastrointestinal tract in animal models.
Seek novel antibody-based therapeutics against CDI.
Investigate the host immune response against C. difficile virulent factors.
Laboratory Personnel
Publications
“The development...Clostridioides difficile infection towards reconstituting gut microbiota."
Zhang Y, Saint Fleur A, Feng H., The development of live biotherapeutics against Clostridioides difficile infection towards reconstituting gut microbiota. Gut Microbes. 2022; 14(1):2052698.
“A probiotic yeast-based immunotherapy against Clostridium difficile infection.”
Chen K, Zhu Y, Zhang Y, Hamza T, Yu H, Saint Fleur A, Galen J, Yang Z, Feng H.A probiotic yeast-based immunotherapy against Clostridium difficile infection. Science translational medicine. 2020; 12(567), eaax4905.
"Cysteine Protease-Mediated Autocleavage of Clostridium difficile...Proinflammatory Activity."
Zhang Y, Li S, Yang Z, Shi L, Yu H, Salerno-Goncalves R, Saint Fleur A, Feng H. Cysteine Protease-Mediated Autocleavage of Clostridium difficile Toxins Regulates Their Proinflammatory Activity. Cell Mol Gastroenterol Hepatol. 2018; 5(4):611-625.
“The role of purified Clostridium difficile glucosylating toxins...a murine cecum injection model."
Zhang Y, Yang Z, Gao S, Hamza T, Yfantis H, Lipsky M, Feng H. The role of purified Clostridium difficile glucosylating toxins in disease pathogenesis utilizing a murine cecum injection model. Anaerobe 2017; S1075-9964(17):30201-9.