Michael Sheedlo, PhD

Dr. Sheedlo attended Michigan State University where he received a B.S. in Biochemistry and Molecular Biology, awarded by Lyman Briggs College. He then transitioned to Purdue University where he earned his PhD from the Department of Chemistry, working in the laboratory of Dr. Chitta Das. After completing his PhD, he obtained a postdoctoral fellowship at Vanderbilt University Medical Center, working under the mentorship of Dr. Borden Lacy. Dr. Sheedlo joined the Department of Pharmacology as an Assistant Professor in 2021.

Sidney P. Colowick Outstanding Postdoctoral Fellow Award, 2020

K99/R00 Career Transition Award, 2020-Present

T32 Training Award Recipient, 2019-2020

Vanderbilt Institute for Infection, Immunology, and Inflammation Postdoc of the Year, 2020

Vanderbilt Institute for Infection, Immunology, and Inflammation Mini-Sabbatical, 2018-2019

Research in the Sheedlo lab is focused on defining the mechanisms that govern interactions at the host-pathogen interface. Specifically, we are interested in using structural biology (cryo-electron microscopy and X-ray crystallography) to obtain a framework that we can then probe in a physiologically relevant context. Of particular interest is understanding how the Gram-positive pathogen, Clostridioides difficile, uses toxins and effectors to elicit disease. In this vein, we are actively pursuing two areas of research (described below).

The Clostridioides difficile Transferase

A primary focus in the Sheedlo lab is an understudied toxin secreted by C. difficile known as the C. difficile transferase (CDT) or binary toxin. Although CDT is not found in all strains of C. difficile, it is produced by some of the most common clinical isolates. The presence of CDT in these strains has led to the hypothesis that the activity associated with CDT may lead to more severe disease outcomes. In the Sheedlo lab, we are interested in elaborating upon the mechanisms used by CDT to intoxicate host cells with the aim of better understanding the role that CDT plays during infection. Through our work, we intend to build upon foundational studies that have defined the structure of CDT and have highlighted features distinct from distantly related toxins such as anthrax toxin.

Gram-positive Type Four Secretion Systems

A second project in the Sheedlo lab aims to improve our understanding of how type four secretion system (T4SS) machinery is arranged and utilized in Gram-positive bacteria. Although T4SSs can be evolutionarily linked to DNA conjugation, several pathogens have evolved to use these complex machines to their advantage during infection. In the Sheedlo lab, we are specifically interested in exploring the utility of a series of T4SS gene clusters recently identified in several strains of C. difficile. Ultimately, our goal is to better understand how C. difficile employs these T4SSs to interact with its environment.

For a complete list of publications, please see: https://www.ncbi.nlm.nih.gov/myncbi/michael.sheedlo.1/bibliography/public/