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SELECTBIO Conferences Extracellular Vesicles (EVs): Technologies & Biological Investigations

Fatah Kashanchi's Biography

Fatah Kashanchi, Professor, George Mason University

Dr. Kashanchi received his Ph.D. in 1990 under the supervision of Dr. Charles Wood who also worked with the Nobel Laureate, Dr. Susumu Tonegawa at MIT. He then moved to National Cancer Institute at NIH’s intramural program and continued his work on RNA viral infections. He is currently a Tenured Faculty in the department of Systems Biology at the Prince William Campus of George Mason University. He has obtained independent funding of more than $15.6 M in funding (NIH, DOD, DOE, and Keck) since his departure from NIH in 2000. He has published 236 peer-reviewed manuscripts (h index = 63), and served as an editorial board and reviewer for number of journal including Cell, Molecular Cell, Nature, Nature Medicine, Science Translational Medicine, Retrovirology, JBC, J. Virol, Virology, NAR, and 4 PLoS journals. He is a regular NIH study section member and has served on 153 panels and chaired 17 since 2000.

For the past eighteen years Kashanchi lab has been interested in 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. They also have ample experience with biochemical pathways that leads to transcription and chromatin remolding using in vitro reconstituted machineries. These complexes with epigenetic modifications utilize host signaling events and therapeutic targets that control viral replication. In recent years, they have also started focusing on Extracellular vesicles (i.e., exosomes) mainly from latent virally infected cells. These cells remain in the body for a long period of time can be extended to the life of a person (i.e., CNS cells). These latent cells produce exosomes that carry markers of the infection including RNA and protein sequences specific to a given virus.

The Kashanchi lab, for the first time, showed that viral release and exosome release have overlapping biogenesis in the ESCRT pathway. For instance, HIV-1 latent cells utilize ESCRT-I for viral release, and ESCRT-II for exosomal release. Using in vitro and in vivo (both patient samples and animal models), the lab has found that exosomes from HIV-1 infected cells carry short non-coding RNAs (i.e., TAR) which regulate TLR3 and other pathways in the recipient cells. This data also implies that endogenous retroviruses may have a similar mode of action in their gene expression by expressing short non-coding RNAs that no only regulate the donor cells, but also the recipient cells through the exosomes transfer pathway. The infected cells (in presence of antiretroviral drugs or innate immune molecules) still secret exosomes that contain viral products including TAR, TAR-Gag RNA, and Nef protein1-7.

Similar results were also observed from other neuro-tropic RNA viral infections including HTLV-1, Ebola, RVFV, and Zika infection. More recently data from HTLV-1 infected HAM/TSP patient showed that exosomes isolated from patient PBMCs (25/35) in ex vivo cultures were Tax positive and patient CSF (7/11) contained Tax+ exosomes but not in HTLV-1 seronegative MS donors (0/5), despite the absence of viral detection in the CSF supernatant. Furthermore, exosomes cultivated from HAM/TSP PBMCs were capable of sensitizing target cells for HTLV-1 specific CTL lysis8.

Collectively, data from Kashanchi lab on exosomes both latent and persistent viral infections (5 RNA viruses tested so far), indicate secretion of exosomes that contain various viral components (RNA and/or proteins), all of which affect the immune cells by either destroying or activating T-cells. Broader implications of these findings in the context of diagnostic and vaccine development are currently under development in the lab.

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Future Directions of EVs and Viruses

Wednesday, 15 December 2021 at 16:15

Add to Calendar ▼2021-12-15 16:15:002021-12-15 17:15:00Europe/LondonFuture Directions of EVs and VirusesExtracellular Vesicles (EVs): Technologies and Biological Investigations in Coronado Island, CaliforniaCoronado Island,

EVs naturally are bioactive containers for delivering various bioactive molecules between cells. A growing body of evidence indicates that such EVs are released from virus-infected cells and transfer viral components between cells including DNA, RNA and proteins, as well as viral receptors mediating entry into recipient cells. The released EVs constitute a range of markers that can serve as biomarker for viral infection both in vitro and in vivo.  These cells release EVs with distinct cargos, which differs from healthy cells and viral infection alters EV loading and biogenesis in donor cells.  The main mechanism of viral cargo release through EVs is alteration in the autophagic pathways, including microautophagy, chaperone-mediated autophagy, macroautophagy, and secretory autophagy.  Specially, secretory autophagy has been shown to be responsible for the secretion of these EVs containing parts of the virus or  EVs that contain fully infectious virions.  Multiple RNA and DNA virally infected cells including HIV-1; CHIKV; HBV; EBV; SV40; PV; IAV; DENV; ZIKV; HTLV-1; HSV-1; KSHV; and MHV-68 utilize alteration of autophagy for their cargo release.  Examples of some of the RNA and DNA viruses that utilize degradative or secretory autophagy in relations to homeostasis or disease will be discussed.

Add to Calendar ▼2021-12-13 00:00:002021-12-15 00:00:00Europe/LondonExtracellular Vesicles (EVs): Technologies and Biological InvestigationsExtracellular Vesicles (EVs): Technologies and Biological Investigations in Coronado Island, CaliforniaCoronado Island,