CONTACT INFORMATIONCREDENTIALSAWARDSPUBLICATIONSJames S. Butler, Ph.D.Contact InformationPhone NumbersOffice: (585) 275-7921Fax: (585) 473-9573Research LabsVisit Lab WebsiteLocationsUniversity of Rochester Medical CenterSchool of Medicine and Dentistry601 Elmwood Ave, Box 672Rochester, NY 14642Faculty AppointmentsProfessor (Part-Time) - Department of Microbiology and Immunology (SMD) BiographyResearchOne goal of the work in the laboratory is a clear understanding of the mechanisms that ensure the proper expression of messenger RNAs in eukaryotes. The research focuses on a nuclear mRNA surveillance pathway in eukaryotes that destroys aberrant RNAs before they exit the nucleus. Central to this pathway is a conserved complex of proteins called the exosome that degrades RNA molecules that fail to undergo post-transcriptional processing reactions such as polyadenylation and splicing. A major unanswered question addressed by the research is what components of the nuclear exosome and the associated TRAMP complex are required for the processing and degradation of RNAs in the nucleus. This RNA surveillance system guards against the formation of defective RNA-protein complexes that have toxic effects on cell growth and proliferation. Previous studies identified Rrp6p, a nuclear exoribonuclease component of the exosome and showed that it plays a critical role in degrading aberrant RNAs in the nucleus. More recent evidence indicates that a second complex called TRAMP plays a key role in activating RNA substrates for degradation by the nuclear exosome. Experiments underway in the lab aim to (i) identify the components of the TRAMP complex required for enhancement of Rrp6p activity, (ii) elucidate the role that TRAMP and Rrp6p play in a general and a specific pathway for mRNA degradation. A second project focuses the public health challenge caused by the resurgence of tuberculosis and the spread of antibiotic resistant strains of the causative agent, Mycobacterium tuberculosis. Tuberculosis kills nearly 2 million people each year and estimates put the worldwide population of infected individuals at nearly 2 billion. A majority of these people (90%) carries latent, asymptomatic infections that reactivate causing disease and spread of M. tuberculosis to uninfected individuals. The latent phase and the slow growth rate of M. tuberculosis limit the effectiveness of existing antibiotics. One approach to treatment of tuberculosis would be to design drugs that inhibit the establishment of the latent phase or reactivate growth under conditions allowing aggressive treatment of the infection. Uncharacterized toxin-antitoxin systems in M. tuberculosis may play a role in the establishment and maintenance of the latent phase of infection. Work in the laboratory is designed to (i) test the hypothesis that activation of these systems induces a static metabolic state in cells, (ii) identify the molecular targets of the toxins and (iii) determine the impact of the loss of Pin-toxin function on M. tuberculosis survival during hypoxia-induced latency. These studies will lay the groundwork for a thorough analysis of the molecular biology of these toxin-antitoxin systems with the goal of designing therapeutic approaches to the treatment of latent M. tuberculosis infections.CredentialsEducation1979BS | Univ Wisconsin-MadisonBiochemistry1984PhD | Univ of Illinois-UrbanaBiochemistryPost-doctoral Training & Residency1987 - 1989University of Rochester, Postdoc., Molec. Biol.1984 - 1987Institut de Biologie Physico-chimique, ParisAwards2017Graduate Alumni AwardSponsor: URMCLocation: URMC2013Outstanding Program Director AwardSponsor: URMCLocation: URMC1983 - 1986NIH - CNRS Postdoctoral Fellowship1983NIH - INSERM Postdoctoral Fellowship - Declined1980 - 1983NIH Predoctoral Traineeship in BiochemistryVIEW ALL expand_morePublicationsJournal Articles1/2019Walling LR, Butler JS. "Toxins targeting transfer RNAs: Translation inhibition by bacterial toxin-antitoxin systems." Wiley interdisciplinary reviews. RNA.. 2019 Jan 0; 10(1):e1506. Epub 2018 Sep 16. 2/1/2018Walling LR, Butler JS. "Homologous VapC Toxins Inhibit Translation and Cell Growth by Sequence-Specific Cleavage of tRNA." Journal of bacteriology.. 2018 Feb 1; 200(3)Epub 2018 Jan 10. 12/15/2016Walling LR, Butler JS. "Structural Determinants for Antitoxin Identity and Insulation of Cross Talk between Homologous Toxin-Antitoxin Systems." Journal of bacteriology.. 2016 Dec 15; 198(24):3287-3295. Epub 2016 Nov 18. VIEW ALL PUBLICATIONSClose WindowSchedule an appointment with James S. Butler, Ph.D.Please answer the following questions to help us find the right appointment for you.Important: If you believe that you have a medical or psychiatric emergency, please call 911 or go to the nearest hospital. This website is not intended for emergency care.Have you seen this provider in the last 2 years?YesNoExisting Patient Schedule or request a follow up appointment online through MyChart. If you do not have a MyChart account, please close this window and call the appointment phone number. James S. Butler, Ph.D. is currently scheduling for the following appointment type(s): Our policy does not permit patients to establish care with multiple providers within the same practice or specialty without prior approval. If you choose a new provider in the same office, we will cancel the appointment. Please contact the office directly with questions on this policy.