University of Gothenburg
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Hadi Valadi

Researcher

Department of Rheumatology and Inflammation
Research
Mail
hadi.valadi@gu.se
Visiting address
Guldhedsgatan 10
51346 Göteborg
Postal address
Box 480
40530 Göteborg

About Hadi Valadi

Associate professor

My name is Hadi Valadi and I am a molecular biologist. In 2003, I received my PhD in Chemistry & Biotechnology from Chalmers technical university under the supervision of Prof. Lena Gustafsson, which was about the functional analysis of three isoenzymes (Glyceraldehyde 3-phosphate dehydrogenase) from the upper part of the glycolysis.

As a Postdoctoral Fellow (2004-2008) I joined Prof. Jan Lötvall’s group at the Institute of Internal medicine at the Sahlgrenska Academy. Under this period we discovered that extracellular vesicles, termed exosomes, transport RNA between cells. The findings suggest a previously undescribed mechanism by which cells send RNA-messages to each other by loading them into exosome-vesicles.

Since 2008, at the dept. of Rheumatology and inflammation research, my research group is studying the mechanism by which a subset of RNAs are packaged into exosomes and how his mechanism can be utilized to insert therapeutic RNAs into exosomes, for delivery to other cells.

Research

Genetic communication between cells via exosome vesicles, the use of exosomes for delivery of therapeutic RNAs to cells

Exosomes are small vesicles (30-150 nm in diameter) secreted by almost all cell types under normal as well as pathological conditions. They have been detected in many biological fluids, as well as supernatants of cultured cells. These vesicles are originated from endocytic pathway, when late endosomes fuse with plasma membrane and release internal vesicles to the extracellular milieu (1). In 2007, we revealed that exosomes from various origins contain a substantial amount of RNA, mainly mRNA and microRNA but contained no or little ribosomal RNA (2). Moreover, we discovered that the exosome vesicles are capable to donate their RNA-content to other cells.

Since exosomes naturally transport genetic materials between cells, we hypothesized that these vesicles - derived from human materials - might be an ideal candidate as delivery vehicle, to deliver therapeutic RNA-molecules to cells/ organs. In order for the exosomes to act as vehicle for delivery of therapeutic RNAs to cells, the exogenous nucleic acids initially need to be introduced into these vesicles.

Our current studies primarily are focused on further understanding the mechanisms by which cells send RNA molecules to each other via exosomes. We have shown that exosomes contain a subset of RNA is released into the extracellular environment via secretion of exosomes. However, the mechanism by which this subset of RNAs are loaded into exosomes, maintained, and transferred to other cells remains unknown. We hypothesized that these RNAs are packaged into exosomes (translocated from cytosol into intraluminal vesicles of endosomes) through the action of specific RNA-binding proteins.

References:

  1. Fevrier, B. and Raposo, G. (2004) Exosomes: endosomal-derived vesicles shipping extracellular messages. Current opinion in cell biology, 16, 415-421.
  2. Valadi, H., Ekstrom, K., Bossios, A., Sjostrand, M., Lee, J.J. and Lotvall, J.O. (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nature cell biology, 9, 654-659.

Group Members

  • Muhammad Nawaz – PostDoc
  • Mehrdad Mokhtari – Master Thesis Student
  • Marco Maugeri – PostDoc

Funding and collaboration

  • Swedish Research Council (VR),
  • Swedish Foundation for Strategic Research (SSF),
  • Swedish government innovation agency (VINNOVA),
  • FoRmulaEx research centre
  • AstraZeneca R&D, Gothenburg

Read more

Akademiliv - The cells’ natural transport system can be used for future treatments