R. Keith Slotkin

R. Keith Slotkin

R. Keith Slotkin

Associate Professor

slotkin.2@osu.edu

Danforth Center
975 N. Warson Rd
St. Louis, MO
63132

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Areas of Expertise

  • Epigenetics
  • Transposable Elements
  • Small RNAs

Education

  • PhD – The University of California Berkeley (2000-2005)
  • Post-Doctoral Research – Cold Spring Harbor Laboratory (2005-2009)
  • Bachelor of Science - The University of Arizona (1996-2000)

Transposable elements are fragments of DNA that can duplicate or move from one location to another. Their ability to replicate has resulted in transposable elements occupying vast amounts of most eukaryotic genomes, including nearly half of the human genome. Although often overlooked or dismissed as “junk DNA”, transposable elements have played an important role in the structure and evolution of the eukaryotic genome.

When transposable elements are active, they cause DNA damage and new mutations by inserting into essential protein-coding genes or by promoting rearrangements and genome instability. To suppress the mutagenic potential of transposable elements, over a billion years ago eukaryotes evolved a genome-wide surveillance system to target transposable elements for inactivation. This process of selective inactivation takes advantage of the transposable element’s propensity to generate double-stranded RNA, which is the trigger for small RNA-based silencing mechanisms. These silencing mechanisms result in either post-transcriptional silencing or chromatin modifications. One such heritable chromatin modification is DNA methylation, which can be propagated from cell to cell (through mitosis) or from parent to progeny (through meiosis and fertilization). This heritable repression of gene expression is referred to as epigenetic regulation, and is not the result of changes in the primary DNA sequence (ATGCs). Epigenetic changes are distinct from genetic changes because they are readily reversible, making them exceptional targets of short-term or generation-to-generation environmental modulation.

For more information on the epigenetic regulation of transposable elements, see Sigman and Slotkin, 2016, The Plant Cell.

My laboratory uses Arabidopsis thaliana (thale cress), a reference flowering plant, as a model to investigate basic biological questions exploring how eukaryotic cells repress transposable elements over the development of a single generation, as well as across evolutionary time. Plants offer a unique opportunity to study transposable elements. Unlike animals, plants lack a germline that is set-aside early in embryonic development, meaning that epigenetic changes that occur during plant development are more likely to be transmitted to the next generation. Furthermore, mutations in the genes responsible for epigenetically suppressing transposable elements in plants are viable, while the corresponding mutations that act similarly to silence transposable elements in mammals are embryonic lethal.

Projects in the laboratory focus on the following:

  1. How the cell recognizes which regions of the genome are genes and should be expressed, and which are transposable elements and should be selectively silenced

  2. How epigenetic information targeting transposable elements for silencing is propagated from generation to generation, protecting each generation from new mutations

  3. How active transposable elements are initially triggered for silencing and how epigenetic modifications are first targeted.

  4. How the recruitment of epigenetic control to transposable elements has been co-opted over evolutionary time to produce novel and interesting examples of gene regulation.

     

Current Lab Members:

Lab Alumni:

  • Germán Martinez-Arias (Postdoc) is currently a Senior Researcher in the laboratory of Claudia Köhler at the Swedish University of Agricultural Sciences
  • Chris DeFraia (Postdoc) is currently an Assistant Professor at Ferris State University
  • Andrea McCue (Graduate Student) is currently a Postdoc at the NIH in the lab of Shiv Grewal
  • Saivageethi Nuthikattu (Graduate Student) is currently a Postdoc at the University of California Davis in the lab of Amparo Villablanca
  • Erica Thomas (Undergraduate Student) is currently in a PhD program at Washington University in St. Louis in the lab of Hani Zaher
  • Jennifer Bosse (Undergraduate Student) is currently in the MCDB Graduate program at The Ohio State University in the lab of Heithem El-Hodiri 
  • Jeff Kovach (Undergraduate Student) is currently studying plant biology in a PhD program at Michigan State University
  • Eric Roose (Undergraduate Student) is currently completing a post-bac pre-med program at the University of Toledo

 

Slotkin Lab Members - 2016

 

Slotkin Lab Members - 2015

 

Slotkin Lab Members - 2012

 

Slotkin Lab Members - 2010

Publications:

Grants, Fellowships and Awards