Bio

Bio


I received a B.S. in Biochemistry and Molecular Biology from UC Santa Cruz, with one year of my bachelor's spent at the Pontifical Catholic University of Chile. Returning to the Bay Area where I grew up, I worked briefly at the VA Medical Center, San Francisco. I then did my Ph.D. studies at MIT, in David Bartel’s lab at the Whitehead Institute. I discovered new features of microRNA recognition sequences that were so predictive of mRNA repression that they were integrated into a major update of TargetScan.org, a microRNA target prediction program that receives ~20,000 visitors per month. I became interested in the link between protein homeostasis and RNA regulation, and joined Dan Jarosz’s lab at Stanford to study novel prion-like states of RNA binding proteins. My interest in prions also led me to a collaboration with Jon Clardy of Harvard, in which we identified for the first time an example of a bacterially secreted molecule that potently induces a prion. I continue to be fascinated with the biologically beneficial roles of prions, how they are induced in nature and the resulting physiological consequences, as well as their characteristic molecular features. Once I complete my training at Stanford I look forward to leading my own research group. In addition to research, I have longstanding interests in science communication for the public (see publications) and celebrating diversity in the academy through outreach opportunities.

Honors & Awards


  • Burroughs Wellcome Fund Postdoctoral Enrichment Program Award, Burroughs Wellcome Fund (2015—2018)
  • Kavli Frontiers of Science Fellow, National Academy of Sciences (2015)
  • Poster Award, Gordon Research Conference: Epigenetics (2015)
  • Ruth L. Kirschstein National Research Service Award (NRSA), NIH/NIGMS (2014—2016)
  • Ford Foundation Postdoctoral Fellowship, Ford Foundation/National Academy of Sciences (2013—2014)
  • MIT Ragnar and Margaret Naess Certificate of Distinction, Jazz Performance (drums), MIT Music and Theater Arts (2012)
  • S. Klein Prize for Science Writing, First Place, Massachusetts Institute of Technology (2012)
  • Phi Beta Kappa, Phi Beta Kappa Society (2004)

Professional Education


  • Doctor of Philosophy, Massachusetts Institute of Technology (2012)
  • Bachelor of Science, University of California Santa Cruz (2004)

Stanford Advisors


Publications

All Publications


  • Intrinsically Disordered Proteins Drive Emergence and Inheritance of Biological Traits. Cell Chakrabortee, S., Byers, J. S., Jones, S., Garcia, D. M., Bhullar, B., Chang, A., She, R., Lee, L., Fremin, B., Lindquist, S., Jarosz, D. F. 2016; 167 (2): 369-381 e12

    Abstract

    Prions are a paradigm-shifting mechanism of inheritance in which phenotypes are encoded by self-templating protein conformations rather than nucleic acids. Here, we examine the breadth of protein-based inheritance across the yeast proteome by assessing the ability of nearly every open reading frame (ORF; ∼5,300 ORFs) to induce heritable traits. Transient overexpression of nearly 50 proteins created traits that remained heritable long after their expression returned to normal. These traits were beneficial, had prion-like patterns of inheritance, were common in wild yeasts, and could be transmitted to naive cells with protein alone. Most inducing proteins were not known prions and did not form amyloid. Instead, they are highly enriched in nucleic acid binding proteins with large intrinsically disordered domains that have been widely conserved across evolution. Thus, our data establish a common type of protein-based inheritance through which intrinsically disordered proteins can drive the emergence of new traits and adaptive opportunities.

    View details for DOI 10.1016/j.cell.2016.09.017

    View details for PubMedID 27693355

  • A common bacterial metabolite elicits prion-based bypass of glucose repression. eLife Garcia, D. M., Dietrich, D., Clardy, J., Jarosz, D. a. 2016; 5

    Abstract

    Robust preference for fermentative glucose metabolism has motivated domestication of the budding yeast Saccharomyces cerevisiae. This program can be circumvented by a protein-based genetic element, the [GAR(+)] prion, permitting simultaneous metabolism of glucose and other carbon sources. Diverse bacteria can elicit yeast cells to acquire [GAR(+)], although the molecular details of this interaction remain unknown. Here we identify the common bacterial metabolite lactic acid as a strong [GAR(+)] inducer. Transient exposure to lactic acid caused yeast cells to heritably circumvent glucose repression. This trait had the defining genetic properties of [GAR(+)], and did not require utilization of lactic acid as a carbon source. Lactic acid also induced [GAR(+)]-like epigenetic states in fungi that diverged from S. cerevisiae ~200 million years ago, and in which glucose repression evolved independently. To our knowledge, this is the first study to uncover a bacterial metabolite with the capacity to potently induce a prion.

    View details for DOI 10.7554/eLife.17978

    View details for PubMedID 27906649

  • Rebels with a cause: molecular features and physiological consequences of yeast prions FEMS YEAST RESEARCH Garcia, D. M., Jarosz, D. F. 2014; 14 (1): 136-147
  • Extreme Tissue Regeneration OZY Magazine Garcia, D. M. 2014
  • Great Adaptations - Research on a versatile bacterium provides insight into multicellular microbial life and tackling deadly infections Natural History Magazine Garcia, D. M. 2012
  • Weak seed-pairing stability and high target-site abundance decrease the proficiency of lsy-6 and other microRNAs NATURE STRUCTURAL & MOLECULAR BIOLOGY Garcia, D. M., Baek, D., Shin, C., Bell, G. W., Grimson, A., Bartel, D. P. 2011; 18 (10): 1139-U75

    Abstract

    Most metazoan microRNAs (miRNAs) target many genes for repression, but the nematode lsy-6 miRNA is much less proficient. Here we show that the low proficiency of lsy-6 can be recapitulated in HeLa cells and that miR-23, a mammalian miRNA, also has low proficiency in these cells. Reporter results and array data indicate two properties of these miRNAs that impart low proficiency: their weak predicted seed-pairing stability (SPS) and their high target-site abundance (TA). These two properties also explain differential propensities of small interfering RNAs (siRNAs) to repress unintended targets. Using these insights, we expand the TargetScan tool for quantitatively predicting miRNA regulation (and siRNA off-targeting) to model differential miRNA (and siRNA) proficiencies, thereby improving prediction performance. We propose that siRNAs designed to have both weaker SPS and higher TA will have fewer off-targets without compromised on-target activity.

    View details for DOI 10.1038/nsmb.2115

    View details for Web of Science ID 000295931400008

    View details for PubMedID 21909094