Research Interests

Cellular memories of a stressful past: encoding by epigenetic regulation of RNA and other mechanisms

A cell or organism's ability to adapt to new environments or stress has major impacts on its evolutionary success, and its potential to transform into diseased states. Genetically encoded traits store selected information that protects against numerous destabilizing forces, experienced over evolutionary timescales. Epigenetic traits can promote rapid phenotypic change, controlling how the complexly evolved genome is expressed upon stress or novel environmental signals.

Our lab aims to uncover, in molecular detail, epigenetic traits that influence how cells respond to stress and adapt to new environments. We mix molecularly focused analyses and high-throughput experiments in yeast to define the drivers of these stress/environment-responsive epigenetic states. We are interested in taking what we learn in yeast and exploring its conservation in metazoans, to understand how these traits can affect human health or influence disease.

RNA Modifying Enzymes with Prion-Like Properties

We place particular focus on regulators of RNA chemical modifications or structure. RNA modifying enzymes (RMEs) can influence expression of numerous genes simultaneously, through molecularly definable rules. Through a large phenotypic screen, based on transient perturbation of more than seventy RMEs and two-dozen other RBPs, we discovered numerous examples of RMEs driving prion-like, heritable growth states. These states influenced fundamental traits such as proliferation, cell size, lifespan, and growth in a variety of stresses. Our goals are to understand the causes and effects of this type of regulation, by connecting long-lasting, heritable changes in RNA regulation to their consequent effects on cell growth across varying environments.

Stress-Induced Epigenetic States

We are also interested in the ability of molecules—both natural and man-made—and environmental stresses to induce new heritable growth states. We previously showed the possibility of identifying environmental molecules responsible for inducing adaptive prions in yeast (Garcia and Dietrich et al., 2016). We then approached this question from a different angle, executing a large phenotypic screen, testing many known molecules and discovering their potential to induce new heritable growth states. We want to identify the genetic and molecular basis of these long-lived states.

Please check out the Garcia lab website for more details.