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SUMMARY:EPFL BioE Talks SERIES  "Metabolic and Stress Response Regulation 
 in Human Hematopoietic and Leukemia Stem Cells"
DTSTART:20211129T160000
DTEND:20211129T170000
DTSTAMP:20260503T103912Z
UID:8f8354bcaec712eaf18f683be9f6e01ad79fa44a69f19b208b9a9416
CATEGORIES:Conferences - Seminars
DESCRIPTION:Stephanie Xie\, Ph.D.\, Princess Margaret Cancer Centre\, Univ
 ersity Health Network\, University of Toronto (Can)\nWEEKLY EPFL BIOE TALK
 S SERIES\n\nAbstract:\nThe hundreds of billions of blood cells produced in
  the body daily are ultimately derived from a rare subpopulation called lo
 ng-term hematopoietic stem cells (LT-HSC). LT-HSC play a central role in m
 aintaining life-long hematopoiesis and are characterized by three function
 al hallmarks: self-renewal\, multilineage differentiation\, and capacity t
 o remain quiescent for long periods of time. Improving our understanding o
 f LT-HSC has implications for a number of diseases including immune system
  disorders\, inherited blood disorders\, and various cancers. Indeed\, som
 e leukemias\, e.g. acute myeloid leukemia (AML)\, are considered stem cell
  diseases that are caricatures of the normal blood system. Inflammatory st
 ress is a major risk factor for many diseases including AML. Severe infect
 ions such as COVID-19 or bacterial sepsis lead to excessive production of 
 pro-inflammatory cytokines (e.g. TNFα) which has been shown to drive lymp
 hopenia\, organ failure\, and mortality in some individuals. Upon stress s
 timuli such as infection\, HSCs must exit quiescence and respond to sudden
  changes in demand. However\, the molecular programs underlying inflammato
 ry stress response in human LT-HSC are not well understood. There is a cri
 tical unmet need to characterize inflammatory stress regulation in human L
 T-HSC and use this knowledge to develop inflammatory stress interventions 
 in disease that spare LT-HSC.\nMetabolism\, derived from the Greek term me
 taballein (to change)\, is intimately tied to the ability for HSCs to tran
 sition from quiescence to a proliferative state. We recently identified th
 at programs involving sphingolipid metabolism and stress response\, includ
 ing inflammatory stress\, regulate human LT-HSC function and show these ar
 e dysregulated in AML. I will discuss how sphingolipid composition is dive
 rse across the human hematopoietic hierarchy and sphingolipid metabolism r
 egulates LT-HSC self-renewal. Sphingosine-1-phosphate (S1P) is a bioactive
  sphingolipid that contributes to a number of inflammatory conditions incl
 uding neurodegeneration\, autoimmunity\, and cardiovascular disease. In a 
 second story\, I will describe how S1PR3 was identified as a TNFa activate
 d S1P receptor whose lentiviral overexpression in LT-HSC was sufficient to
  promote cell cycle activation\, drive myeloid differentiation and led to 
 decreased reconstitution in xenografts akin to a chronic inflammation-indu
 ced emergency myelopoiesis response. Functional studies involving modulati
 on of the S1P signaling axis\, including with the S1P prodrug FTY720\, in 
 LSCs induced differentiation and reduced engraftment ability\, pointing to
  a novel therapeutic approach in AML. Finally\, I will discuss a new proje
 ct seeking to characterize the effect of pro-inflammatory stress on human 
 LT-HSC and identify potential novel metabolic pathways that prevent HSC fu
 nctional impairment due to pro-inflammatory stress exposures. Preliminary 
 data suggest TNFα elicits heterogeneous responses from the human LT-HSC p
 ool with some cells primed to respond and others more resistant to the neg
 ative impact of TNFα treatment.\n\nBio:\nStephanie Xie is an affiliate sc
 ientist (equivalent to a research assistant professor) at the Princess Mar
 garet Cancer Centre in the University Health Network. She obtained her PhD
  from the Department of Biology at the Massachusetts Institute of Technolo
 gy with Dr. Peter Sorger\, moved to a post-doctoral fellowship in Dr. Davi
 d Scadden’s group at Massachusetts General Hospital/Harvard Stem Cell In
 stitute and then finished her post-doctoral training in Dr. John Dick’s 
 group at the Princess Margaret Cancer Centre. She is one of the leading ex
 perts of human HSC assays/analysis. She has been at the forefront in the f
 unctional characterization of stemness programs in human hematopoietic ste
 m cells (HSCs) and how they are perturbed in leukemia stem cells (LSCs) fr
 om acute myeloid leukemia (AML). She identified that sphingolipids interse
 ct with stemness regulatory programs including inflammatory and proteostat
 ic quality control pathways to regulate cell fate in human HSCs and this h
 as been subverted in patient LSCs. Understanding lipid metabolism in stem 
 cells holds great translational promise including improving HSC transplant
 ation and targeting AML. \n\n\n\n\nZoom link (with one-time registration 
 for the whole series) for attending remotely: https://go.epfl.ch/EPFLBioET
 alks\n\nIMPORTANT NOTICE:\nThis seminar can be followed via Zoom web-strea
 ming only\, (following prior one-time registration through the link above)
 .\n\n\n\nInstructions for 1st-year Ph.D. students who are under EDBB’s m
 andatory seminar attendance rule:\nPlease make sure to\n\n	send D. Reinhar
 d a note before noon on seminar day\, informing that you plan to attend th
 e talk online\, and\n	be signed in on Zoom with a recognizable user name (
 not a pseudonym making it difficult or impossible to be identified).\n
LOCATION:via Zoom web-streaming only https://go.epfl.ch/EPFLBioETalks http
 s://go.epfl.ch/EPFLBioETalks
STATUS:CONFIRMED
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