Charles Darkoh
Professor and R. Palmer Beasley, M.D. & Lu Yu Hwang, M.D. Endowed Chair in Infectious Diseases and Global Health
The University of Texas Health Science Center at Houston
School of Public Health
Department of Epidemiology
Center for Infectious Diseases
My laboratory focuses on microbial pathogenesis, molecular epidemiology, and the molecular basis of enteric infectious diseases to identify and understand the mechanisms of action of novel virulence factors, pathways, and unique microbial products that can be harnessed for diagnostics and therapeutics. My long-term research interests include examining the role of microbially-produced small molecules and metabolites in the pathogenesis of enteric infectious diseases, mechanisms of host-pathogen interactions, antimicrobial resistance, drug discovery, host genetics and susceptibility to bacterial infections, and developing new genetic systems for bacterial pathogenesis studies.
One of the current projects in my laboratory involves elucidating the mechanism of toxin regulation in Clostridioides difficile, a multidrug-resistant pathogen responsible for the majority of the hospital-acquired and antibiotic-associated diarrhea in the United States with an estimated total cost of treatment of about 5 billion U.S. dollars annually. This anaerobic bacterium causes disease by producing toxins. We discovered for the first time that C. difficile regulates the production of its disease-causing toxins using a unique small quorum-signaling cyclic peptide, which is released by the infecting bacteria and accumulates in the colon during infection. Furthermore, my laboratory has identified a novel pathway in C. difficile, which produces the cyclic peptide important for making its toxins. This has enabled us to identify novel compounds that block the pathway and toxin production. We have also identified another group of compounds that inhibit toxin activity. These discoveries offer exciting new avenues for developing novel non-antibiotic therapies for treating both initial and recurrent C. difficile infections. A long-term goal of my laboratory is to understand all of the players and mechanisms involved in C. difficile toxin regulation, which I anticipate will allow us to develop novel therapeutics to combat this life-threatening emerging multidrug-resistant pathogen.
A tutorial student in my laboratory will gain experience working with clinical aerobic and anaerobic pathogens, animal models of enteric infections, learn various molecular biology, microbial genetics, and biochemical techniques in a translational research setting.
Education & Training
PhD, MD Anderson UTHealth Houston Graduate School, 2012