J Scott Butler, Ph.D.

J Scott Butler, Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 672
Rochester, NY 14642

Office: (585) 275-7921
Lab: (585) 275-5614
Fax: (585) 473-9573

Research Bio

One 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.

Awards & Honors (National)

NIH - CNRS Postdoctoral Fellowship 1983 - 1986
NIH - INSERM Postdoctoral Fellowship - Declined 1983
NIH Predoctoral Traineeship in Biochemistry 1980 - 1983

Recent Journal Articles

Showing the 5 most recent journal articles. 44 available »

2016 Sep 26
Walling LR, Butler JS. "Structural determinants for antitoxin identity and insulation of cross talk between homologous toxin-antitoxin systems." Journal of bacteriology. 2016 Sep 26; Epub 2016 Sep 26.
2016 Mar
Uppal N, Foxe JJ, Butler JS, Acluche F, Molholm S. "The neural dynamics of somatosensory processing and adaptation across childhood: a high-density electrical mapping study." Journal of neurophysiology. 2016 Mar; 115(3):1605-19. Epub 2016 Jan 13.
2015 Oct 14
Seward CH, Manzella A, Alam A, Butler JS, Dziejman M. "Using S. cerevisiae as a Model System to Investigate V. cholerae VopX-Host Cell Protein Interactions and Phenotypes." Toxins. 2015 Oct 14; 7(10):4099-110. Epub 2015 Oct 14.
2015 Apr
Jin G, Pavelka MS, Butler JS. "Structure-function analysis of VapB4 antitoxin identifies critical features of a minimal VapC4 toxin-binding module." Journal of bacteriology. 2015 Apr; 197(7):1197-207. Epub 2015 Jan 26.
2015 Apr
Aroda VR, Christophi CA, Edelstein SL, Zhang P, Herman WH, Barrett-Connor E, Delahanty LM, Montez MG, Ackermann RT, Zhuo X, Knowler WC, Ratner RE, . "The effect of lifestyle intervention and metformin on preventing or delaying diabetes among women with and without gestational diabetes: the Diabetes Prevention Program outcomes study 10-year follow-up." The Journal of clinical endocrinology and metabolism. 2015 Apr; 100(4):1646-53. Epub 2015 Feb 23.

Current Appointments

Professor - Department of Microbiology and Immunology (SMD) - Primary
Professor - Department of Biochemistry and Biophysics (SMD)

Education

PhD | Biochemistry | Univ of Illinois-Urbana1984
BS | Biochemistry | Univ Wisconsin-Madison1979

Post-Doctoral Training & Residency

University of Rochester, Postdoc., Molec. Biol. 1989
Institut de Biologie Physico-chimique, Paris 1987