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SELECTBIO Conferences Extracellular Vesicles (EV)-Exosomes: Diagnostics, Delivery and Therapeutics

Fatah Kashanchi's Biography



Fatah Kashanchi, Professor, George Mason University

Dr. Kashanchi is a Professor and currently at head of the Laboratory of Molecular Virology at the George Mason University. He has obtained more than $15.8 M in funding (NIH, DOD, DOE, and Keck) since his departure from NIH’s intramural program in 2000. He has published more than 218 peer-reviewed manuscripts (h index = 57) and served as an editorial board and reviewer for journals such as JBC, Retrovirology, J. Virol, Virology, NAR, 4 PLoS Journals, Cell, Molecular Cell, Nature Medicine, Nature communications, Scientific Report and Science Translational Medicine.

His lab focuses on understanding the mechanism of viral gene expression in human viruses and how the virus and the host control the dynamics of fundamental machineries needed for viral replication and/or host survival, including pathways that leads to transcription and chromatin remolding using in vitro reconstituted DNA/RNA elements. His lab has also contributed to general understanding of how these machineries are different in T-cells vs. myeloid cells. In recent years, his lab has additionally been focusing on exosomes secreted from HIV and HTLV infected cells, as well as 7 other RNA and DNA virus infections (through collaborations) and validation of data using in vitro functional analysis and humanized mouse models. The more recent exosome works focus on the mechanisms of how autophagy regulates EV biogenesis and how viruses manage to deregulate autophagy. Finally, in collaborations with ATCC, they have purified large-scale iPSC and MSC EVs as reparative agents.

Fatah Kashanchi Image

Exosomes and Viruses: A Tale of Two Overlapping Worlds

Friday, 26 February 2021 at 08:00

Add to Calendar ▼2021-02-26 08:00:002021-02-26 09:00:00Europe/LondonExosomes and Viruses: A Tale of Two Overlapping WorldsExtracellular Vesicles (EV)-Exosomes: Diagnostics, Delivery and Therapeutics in Virtual ConferenceVirtual ConferenceSELECTBIOenquiries@selectbiosciences.com

Extracellular vesicles (EVs) play a significant role in intercellular communication by serving as a carrier for the transfer of membrane and cytosolic proteins, lipids, and RNA between cells.  In recent years, using state of art technologies such as RNA seq, RPMA, and single cell omics, we have found that virally infected cells including HIV-1, HTLV-1, Rift Valley Fever, Zika, Ebola, and Coronavirus infected cells secret exosomes that contain biomarker of these infections in urine, saliva, CSF, and blood. We have been able to separate and characterize EVs from several different viruses including HIV-1.  These EVs are not infectious and have a different density than infectious virions using gradients.  They contain various viral RNAs including TAR (non-coding RNA), Nef, gp120/160 and Tat.  The origin of these EVs are infected cells, especially when treated with cART or Interferons.  They are present in patient samples tested (plasma and CSF, 33%-95%) to date (4 cohorts of 5-20 patients each). The EVs contribute to pro-inflammatory signals in the naïve recipient cells using TLR3 signaling.  Recently, we have asked about the timing difference between EV and virus release from infected cells using serum starvation experiments from cells followed by release. Results from supernatants of uninfected cells showed a peak of tetraspanin proteins (CD63, CD81, and CD9) at 6 hours and a gradual decrease of all EV associated proteins by 24 hours. However, the EV from HIV-1 infected cells showed all three tetraspanins present at 3 hours and expression gradually increased up to 24 hours. HIV-1 viral proteins (p24, gp120, Nef) expression was present at 6 hours and continued to increase and peaked at 24 hours.  HIV-1 supernatant 6- hour sample was found not to be infectious. However, infectious HIV-1 was successfully rescued from 24-hour sample.

Our data indicates that EV release may occur prior to viral release in infected cells, thereby implicating a potentially significant effect of EVs on uninfected recipient cells prior to subsequent viral infection.


Add to Calendar ▼2021-02-25 00:00:002021-02-26 00:00:00Europe/LondonExtracellular Vesicles (EV)-Exosomes: Diagnostics, Delivery and TherapeuticsExtracellular Vesicles (EV)-Exosomes: Diagnostics, Delivery and Therapeutics in Virtual ConferenceVirtual ConferenceSELECTBIOenquiries@selectbiosciences.com