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SUMMARY:EPFL BioE Talks SERIES  "The Glycosphingolipid Gb3 as Target for P
 athogens and Cancer Immunotherapy"
DTSTART:20240415T121500
DTEND:20240415T131500
DTSTAMP:20260916T085034Z
UID:06983be0898a7a55263ff004b1828f049f0d08f7e046fc425a2716cf
CATEGORIES:Conferences - Seminars
DESCRIPTION:Prof. Winfried Römer\, Faculty of Biology and Signalling Rese
 arch Centres BIOSS and CIBSS\, University of Freiburg (DE)\nWEEKLY EPFL BI
 OE TALKS SERIES (sandwiches provided)\n\nAbstract:\nGlycosphingolipids (GS
 Ls) are mainly present in the extracellular leaflet of the plasma membrane
 . They are known to be involved in many cellular processes\, e.g. in signa
 l transduction\, cell differentiation\, apoptosis or embryonic development
 . However\, a more precise characterization of the physiological role of G
 SLs is difficult due to the lack of appropriate tools.\n\nThis presentatio
 n focuses on the glycosphingolipid Gb3\, also known as globotriaosylcerami
 de\, CD77 and Pk blood group antigen. It represents an attractive host cel
 l receptor\, particularly for pathogens and pathogenic products. Shiga tox
 in (Stx)\, from Shigella dysenteriae or Escherichia coli\, which is one of
  the most virulent bacterial toxins\, binds and clusters Gb3\, leading to 
 local negative membrane curvature and the formation of tubular plasma memb
 rane invaginations as the initial step for clathrin-independent endocytosi
 s. After internalization\, Stx is embracing the retrograde transport pathw
 ay. In comparison\, the homotetrameric lectin LecA from the bacterium Pseu
 domonas aeruginosa can also bind to Gb3\, triggering the so-called lipid z
 ipper mechanism\, which results in membrane engulfment of the bacterium as
  an important step for its cellular uptake. Notably\, both lectins bind to
  Gb3 but induce distinct plasma membrane domains and exploit mainly differ
 ent transport pathways. What makes the difference?\n\nThe second part of t
 he presentation will focus on the glycosphingolipid Gb3 as target for canc
 er immunotherapy. Gb3 is highly abundant in various cancers\, such as Burk
 itt's lymphoma\, colorectal or breast cancer. Proof-of-concept studies of 
 lectin-based approaches (so-called lectibodies and lectin-CAR T cells)\, w
 hich redirect the immune system into fighting cancer\, will be introduced.
 \n\nThe lectibody is a bispecific construct composed of a Gb3-binding lect
 in linked to an antibody fragment. It was inspired by bispecific T cell en
 gager (BiTEs) antibodies that recruit cytotoxic T lymphocytes while simult
 aneously binding to tumor-associated antigens on cancer cells. In another 
 approach\, a panel of Gb3-binding lectin-CAR T cells was developed. Both t
 ools resulted in a specific and nearly complete tumor cell lysis in vitro.
  These findings reveal the big potential of lectibodies and lectin-based C
 AR T cells as therapeutical applications to target Gb3 and other tumor-ass
 ociated carbohydrate antigens expressed in hematological malignancies and 
 solid tumors.\n\n\nBio:\nWinfried Römer is Professor of Synthetic Biology
  of Signalling Processes at the Faculty of Biology and member of the BIOSS
  and CIBSS signaling research centers at the University of Freiburg (Germa
 ny) since 2011. From 1996-2001\, he studied chemistry and biology at the U
 niversity of Regensburg (Germany)\, where he also performed his PhD studie
 s (2001-2004). As post-doctoral fellow (2004-2008) and research scientist 
 CNRS (2008-2011) at Curie Institute (Paris\, France)\, he investigated nov
 el uptake pathways used by several toxins and viruses. Together with a col
 league\, he was awarded the Pfizer Foundation Research Prize (Infectiology
 ) in 2011.\n\nHis research is mainly focused on host-pathogen interactions
 \; in particular\, he is interested in understanding the impact of bacteri
 al lectins on host cell physiology of single cells\, tissues and model org
 anisms in molecular detail by using a combination of analytical and synthe
 tic approaches. For instance\, his lab investigates the effects of the P. 
 aeruginosa lectins LecA and LecB on wound healing processes (e.g. cell pro
 liferation\, cell adhesion and migration\, immune response). Moreover\, in
  collaboration with chemists he develops alternative strategies to fight b
 acterial infections\, e.g. divalent glycomimetics that fully block host ce
 ll invasion when applied in nano-molar concentrations\, or bacteriophages 
 to kill intracellular bacteria. Recently\, he started to develop lectin-ba
 sed tools to target and kill cancer cells.\n\n\nZoom link (with one-time r
 egistration for the whole series) for attending remotely: https://go.epfl.
 ch/EPFLBioETalks\n\n\nInstructions for 1st-year Ph.D. students who are und
 er EDBB’s mandatory seminar attendance rule:\nIN CASE you cannot attend 
 in-person in the room\, please make sure to\n\n	send D. Reinhard a note we
 ll ahead of time (ideally before seminar day)\, informing that you plan to
  attend the talk online\, and\, during seminar:\n	be signed in on Zoom wit
 h a recognizable user name (not any alias making it difficult or impossibl
 e to identify you).\n\nStudents attending the seminar in-person should col
 lect a confirmation signature after the talk - please print your own signa
 ture sheet beforehand (71 kB pdf available for download here). IMPORTANTLY
 : hang on to this sheet as no signature record is being kept by anyone els
 e!
LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717 https://go.epfl.ch/
 EPFLBioETalks
STATUS:CONFIRMED
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