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Aishe Sarshad - Research
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Research Summary

An illustrative model of Micro RNA

Non-coding RNAs and AGOs in Health and Disease

Argonaute (AGO) proteins, loaded with small interfering RNAs (siRNAs) or microRNAs (miRNAs), are the core components of RNA induced silencing complex (RISC). The small RNAs guide the AGO ribonucleoprotein to complementary target RNAs resulting in gene silencing. microRNAs (miRNAs), 21-23 nucleotide long non-coding RNA molecules, are expressed in a cell type-specific manner and can accumulate to tens of thousands of copies per cell. It is estimated that up to 60% of human genes are under miRNA regulation. miRNA silencing pathways play important roles in a number of biological processes, including embryonic stem cell differentiation and tissue development. Deregulation of this pathway is associated with various diseases; therefore, it is essential to fully understand the molecular mechanisms of miRNA regulation.    

We recently discovered that key factors of the RISC silencing complex are expressed in the nucleus of embryonic stem cells. Our current work aims at decoding the regulatory pathways of nuclear RISC. Specifically, we want to understand why stem cells need nuclear miRNA-Argonaute complexes for gene regulation and how these play a role during stem cell differentiation and reprograming. We further aim to understand if nuclear RNA interference by RISC can be used in cancers as a way of targeting nuclear factors important in cancer development.

A portrait of Aishe Sarshad
Photo: Johan Wingborg

Contact Information

Department of Medical Biochemistry and Cell biology
Phone +46 31-786 57 04
Mail: aishe.sarshad@gu.se

Visiting Address
Medicinaregatan 9 a-b
41390 Göteborg

Postal Address
Box 440
40530 Göteborg

Grants and Awards

Establishment grants:

  • 2020     Tenure-track position with Wallenberg Center for Molecular and Translational Medicine
  • 2019     Swedish Society for Medical research (SSMF) 
  • 2019     The Swedish Research council (VR) 

Project funding

  • 2021     Åke Wiberg foundation (awarded 2019, 2020 and 2021)
  • 2021     Magnus Bergvall foundation (awarded 2019, 2020 and 2021)
  • 2021     Ollie och Elof Ericsson foundation (awarded 2020 and 2021)
  • 2020    Cornell foundation (awarded 2019 and 2020) 
  • 2020    The Swedish Medical Society (SLS) 
  • 2020    Jeansson foundation 
  • 2020    AG-Fonden (Awarded 2019 and 2020)
  • 2020    Carl Trygger foundation 
  • 2019    Gunvor och Josef Anérs foundation 
  • 2018    Olle Engkvist foundation
  • 2018    Sahlgrenska Academy Returning Grant

Awards:

  • 2019    L’Oréal-UNESCO for Women in Science Award, Sweden 
  • 2016    Fellow Award Research Excellence (FARE), NIH

Postdoc grants:

  • 2016    The Swedish Research council (VR)
  • 2016     Swedish Society for Medical research (SSMF) – declined

Group Members

Vivian Lobo, Postdoctoral fellow

  • PhD in Reproductive Medicine, University of Mumbai, India
  • MSc, in Biotechnology, University of Mumbai, India
  • BSc, in Biotechnology, University of Mumbai, India

Carola Fernandez, Postdoctoral fellow

  • PhD in Medical Biology University of Montpellier, France
  • MSc in Stem cell and developmental Biology, Sorbonne University, France
  • BSc in Life Science biology, Sorbonne University, France

Iwona Nowak, Postdoctoral fellow

  • PhD in Biochemistry, biophysics and Biotechnology, University of Jagiellonian University, Poland

  • MSc in Biotechnology, University of Jagiellonian University, Poland
  • BSc in Biotechnology, University of Jagiellonian University, Poland

Ulrika Alexandersson, Lab manager (shared with Maria Falkenberg)

  • BSc University of Gothenburg, Sweden

Alumni

Isra Hamzo, BMA thesis student
Wail Chrifi, Technician

Selected Publications

Nowak I and Sarshad AA#
Argonaute proteins take center stage in cancers.
Cancers (2021) 13(4):788.
doi.org/10.3390/cancers13040788

Muys BR, Sousa JF, Pla.a JR, Ara.jo LF, Sarshad AA, Anastasakis DG, Wang X, Li XL, de Molfetta GA, Ram.o A, Lal A, Vidal DO, Hafner M, Silva WA.
miR-450a acts as a tumor suppressor in ovarian cancer by regulating energy metabolism.
Cancer Research. (2019) Jul 1;79(13):3294-3305.
doi: 10.1158/0008-5472.CAN-19-0490

Sarshad AA, Juan AH, Correa Muler AI, Anastasakis D, Wang X, Genzor P, Feng X, Tsai P, Sun H, Haase AD, Sartorelli V, Hafner M.
Argonaute-miRNA complexes silence target mRNAs in the nucleus of mammalian stem cells.
Molecular Cell. (2018) Sep 20;71(6):1040-1050.e8
doi: 10.1016/j.molcel.2018.07.020.

Gao QQ*, Putzbach WE*, Murmann AE, Chen S, Sarshad AA, Ambrosini G, Bartom ET, Hafner M, and Peter ME.
6mer seed toxicity in tumor suppressive microRNAs.
Nature Communications (2018), Oct 29;9(1):4504.
doi: 10.1038/s41467-018-06526-1.

Tsai P, Dell’Orso S, Rodriguez J, Vivanco KO, Ko K, Jiang K, Juan AH, Sarshad AA, Tran M, Wang D, Wang AH, Anastasakis D, Ralston E, Ried T, Sun H, Hafner M, Larson DR, and Sartorelli V. A
Muscle Super-Enhancer RNA Mediates Cohesin Recruitment and Regulates Transcription in Trans.
Molecular Cell. (2018) Jul 5;71(1):129-141.e8.
doi: 10.1016/j.molcel.2018.06.008.
 
Benhalevy D*, McFarland HL*, Sarshad AA*, Hafner M.
PAR-CLIP and streamlined small RNA cDNA library preparation protocol for the identification of RNA binding protein target sites.
Methods. (2017) Apr 15;118-119:41-49.
doi: 10.1016/j.ymeth.2016.11.009

Dutka T*, Sarshad AA*, Hafner M.
PAR-CLIP: A Genomic Technique to Dissect RNA-Protein Interactions.
Field Guidelines for Genetic Experimental Designs in High-Throughput Sequencing (2016) pp 261-289.
Doi 10.1007/978-3-319-31350-4