Astrid D. Haase, M.D., Ph.D.

Stadtman Investigator

RNA Biology Section, Laboratory of Cell and Molecular Biology

NIDDK

BG 8A RM 1A04
8 CENTER DR
BETHESDA MD 20892

301-451-5125

astrid.haase@nih.gov

Research Topics

Research Goal

We aim to understand how small non-coding RNAs guard genomic integrity.

Current Research

Small non-coding RNAs play crucial roles in development and disease. Globally referred to as RNA interference (RNAi), conserved small RNA pathways operate from yeast to human. They regulate gene expression, defend against viruses and control repetitive genetic elements. Additionally, their elegant mechanisms are widely harnessed for biotechnology and targeted therapy.

Our group studies a particular class of small RNAs that represses transposon activity in the germline. The ability of transposons to mobilize and insert into new genomic locations threatens genomic integrity and must be suppressed. Integrity of genomic information is particularly important in germ cells that determine the genetic make-up of a species. Therefore germ cells employ specialized small RNA pathways -PIWI proteins and PIWI-interacting RNAs (piRNAs)- to silence transposons and thus ensure genomic stability and fertility in animals. Mature piRNAs guide their associated PIWI complexes to silence transposons at transcriptional or post-transcriptional levels, directing chromatin modifications or promoting RNA decay.

We aim to elucidate molecular mechanisms of piRNA silencing through an integrated approach combining Drosophila genetics, biochemistry and next-generation sequencing. While recent advances have provided a framework for what resembles a small RNA-based immune system, further studies are required to elucidate the many molecular innovations that enable discrimination of transposons from host genes and efficient selective silencing of genetic mobility. Successfully meeting our goals will bolster our understanding of fundamental mechanisms that survey and guard genomic integrity.

Applying our Research

Genome integrity is essential for cellular and organismal fitness and is lost in various diseases including cancer. Insights into the molecular mechanisms of small RNA-guided genome defense will further our understanding of genome surveillance, and will inspire novel biomedical approaches to combat genomic instability in diseases. Additionally, mechanisms of RNA interference have been successfully harnessed for biotechnology and targeted therapy over the past years, and novel insights into piRNA pathways will enlarge our molecular repertoire.

Need for Further Study

Small regulatory RNAs have been discovered in all branches of life but we are just beginning to understand their diverse functions in gene regulation and genome surveillance. Further studies are required to characterize these regulatory pathways and to elucidate their molecular mechanisms.

Biography

  • Post Doctoral Fellow, Cold Spring Harbor Laboratory, 2007-2015
  • Graduate Student, Friedrich Miescher Insitute for Biomedical Research, 2002-2007
  • Ph.D., University of Basel, Switzerland, 2007
  • M.D., University of Vienna, Austria, 2002

Selected Publications

  1. Yang M, Haase AD, Huang FK, Coulis G, Rivera KD, Dickinson BC, Chang CJ, Pappin DJ, Neubert TA, Hannon GJ, Boivin B, Tonks NK. Dephosphorylation of tyrosine 393 in argonaute 2 by protein tyrosine phosphatase 1B regulates gene silencing in oncogenic RAS-induced senescence. Mol Cell. 2014;55(5):782-90.

  2. Faehnle CR, Elkayam E, Haase AD, Hannon GJ, Joshua-Tor L. The making of a slicer: activation of human Argonaute-1. Cell Rep. 2013;3(6):1901-9.

  3. Ipsaro JJ, Haase AD, Knott SR, Joshua-Tor L, Hannon GJ. The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis. Nature. 2012;491(7423):279-83.

  4. Elkayam E, Kuhn CD, Tocilj A, Haase AD, Greene EM, Hannon GJ, Joshua-Tor L. The structure of human argonaute-2 in complex with miR-20a. Cell. 2012;150(1):100-10.

  5. Haase AD, Fenoglio S, Muerdter F, Guzzardo PM, Czech B, Pappin DJ, Chen C, Gordon A, Hannon GJ. Probing the initiation and effector phases of the somatic piRNA pathway in Drosophila. Genes Dev. 2010;24(22):2499-504.


This page was last updated on June 20th, 2017