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SUMMARY:ChemBio seminar by Dr Xuyu Liu (Uni Sydney) - CH-635
DTSTART:20240625T091500
DTEND:20240625T101500
DTSTAMP:20260926T055229Z
UID:09d08044436198f75f5a0cdc511c6efb67523a5a6a6b152d583350af
CATEGORIES:Conferences - Seminars
DESCRIPTION:Dr Xuyu Liu\nTitle: Unveiling hidden functions of dietary elec
 trophiles in platelets through integrated phenotypic and chemoproteomic ap
 proaches\n\nAbstract:\nA wide range of dietary phytochemicals has been sho
 wn to modulate the activities of kinases\, ubiquitin-conjugating enzymes\,
  and transcription factors\, providing long-lasting impacts on immune resp
 onses\, neural plasticity\, and cardiovascular health.1 Many of these bioa
 ctive compounds possess electrophilic functionalities\, enabling covalent 
 attachment to the sulfhydryl side chains of cysteine residues within prote
 ins.2 Such diet-induced covalent modifications have recently been linked t
 o a reduced risk of acute ischemic stroke and atherosclerosis.3\, 4 Despit
 e these findings\, the effects of protein post-dietary modifications on th
 e functions and activities of platelets – crucial cellular elements in r
 egulating hemostasis and thrombosis – remain largely unexplored.\nIn our
  recent investigation\, we analyzed platelet phenotypes resulting from the
  irreversible binding of proteins by 23 dietary electrophiles.5 This analy
 sis revealed distinct antiplatelet selectivity profiles for naturally occu
 rring isothiocyanates and polyphenols\, notably attenuating the platelets'
  response to the ADP agonist without affecting thrombin-mediated activatio
 n. By integrating a Click chemistry-based target enrichment strategy with 
 a multiplexed Tandem Mass Tag (TMT) proteomic mapping approach\, we identi
 fied protein disulfide isomerase isoform A6 (PDIA6) as the key target modi
 fied through covalent bonds with these dietary electrophiles. Importantly\
 , using murine models of electrolytic injury-induced thrombosis and tail b
 leeding\, we demonstrated that selective inhibition of PDIA6 is effective 
 in thrombolytic therapy in vivo without an increased risk of bleeding. Our
  findings suggest a new avenue for developing antiplatelet agents based on
  the mechanism of diet-induced electrophilic modifications\, potentially o
 ffering safer and more effective therapeutic options for the treatment of 
 stroke and thrombosis.\nReferences:\n(1) Manju Singh\, M.\; Arvind\, K. S.
 \; Raosaheb\, K. In Antioxidants\, Viduranga\, W. Ed.\; IntechOpen\, 2021.
 \n(2) Long\, M. J. C.\; Liu\, X.\; Aye\, Y. Current Opinion in Chemical Bi
 ology 2019\, 51\, 48-56.\n(3) van Steenwijk\, H. P.\; Winter\, E.\; Knaven
 \, E.\; et al. Frontiers in Nutrition 2023\, 10\, Clinical Trial.\n(4) Rud
 olph\, T. K.\; Rudolph\, V.\; Edreira\, M. M.\; et al. Arteriosclerosis\, 
 Thrombosis\, and Vascular Biology 2010\, 30\, 938-945.\n(5) Guan\, I. A.\;
  Liu\, J. T.\; Sawyer\, R. C.\; et al. ACS Central Science 2024\, 10\, 344
 -357.\n\n \nSpeaker's biography:\nDr Xuyu (Johnny) Liu completed his Bach
 elor and Master of Biomedical Science at Victoria University\, Wellington\
 , NZ in 2012. He then moved to Sydney and conducted his PhD research under
  the supervision of Professor Richard J Payne in the School of Chemistry a
 t The University of Sydney and graduated in 2016. His PhD research entaile
 d developing new methods for sulfopeptide synthesis and evaluating sulfope
 ptides’ biological activity. In his postdoctoral work\, he worked at Cor
 nell University and École Polytechnique Fédérale de Lausanne (EPFL) und
 er the guidance of Prof Yimon Aye. His postdoctoral research focused on hi
 jacking endogenous lipid electrophile-signalling pathways for precision me
 dicine development. The contribution of this work to anticancer research w
 as recognised by Cornell University\, and he was nominated by the universi
 ty for the Blavatnik Award in 2018.\nDr Liu was awarded the Sydney Cardiov
 ascular Fellowship and joins HRI to start his independent research in deve
 loping new chemoproteomic platforms for identification of novel therapeuti
 c targets for cardiovascular disease.\n\nLab website: https://www.hri.org.
 au/our-research/cardiovascular-protective-signalling-and-drug-discovery\n\
 n 
LOCATION:CE 1 5 https://plan.epfl.ch/?room==CE%201%205
STATUS:CONFIRMED
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