Astrid Desiree Haase, M.D., Ph.D.
RNA Biology Section, Laboratory of Cell and Molecular Biology
Building 8A, Room 1A04
8 Center Dr
Bethesda, MD 20814
+1 301 451 5125
We aim to understand how small non-coding RNAs guard genomic integrity.
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.
- Post Doctoral Fellow, Cold Spring Harbor Laboratory, 2007-2015
- Graduate Student, Friedrich Miescher Institute for Biomedical Research, 2002-2007
- Ph.D., University of Basel, Switzerland, 2007
- M.D., University of Vienna, Austria, 2002
Genzor P, Cordts SC, Bokil NV, Haase AD. Aberrant expression of select piRNA-pathway genes does not reactivate piRNA silencing in cancer cells. Proc Natl Acad Sci U S A. 2019.
Stein CB, Genzor P, Mitra S, Elchert AR, Ipsaro JJ, Benner L, Sobti S, Su Y, Hammell M, Joshua-Tor L, Haase AD. Decoding the 5' nucleotide bias of PIWI-interacting RNAs. Nat Commun. 2019;10(1):828.
Sarshad AA, Juan AH, Muler AIC, Anastasakis DG, Wang X, Genzor P, Feng X, Tsai PF, Sun HW, Haase AD, Sartorelli V, Hafner M. Argonaute-miRNA Complexes Silence Target mRNAs in the Nucleus of Mammalian Stem Cells. Mol Cell. 2018;71(6):1040-1050.e8.
Haase AD. A Small RNA-Based Immune System Defends Germ Cells against Mobile Genetic Elements. Stem Cells Int. 2016;2016:7595791.
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.
Related Scientific Focus Areas
Genetics and Genomics
Molecular Biology and Biochemistry
This page was last updated on October 25th, 2019