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UID:966@biology.technion.ac.il

DTSTART;TZID=Asia/Jerusalem:20210706T130000

DTEND;TZID=Asia/Jerusalem:20210706T140000

DTSTAMP:20210802T125905Z

URL:https://biology.technion.ac.il/en/seminars/phd-graduate-seminar-elleno
 re-koren-2/

SUMMARY:PhD Graduate Seminar-Ellenore Koren [No Categories]
DESCRIPTION:Location:   \n Affiliation: \n Host:\n Stem Cells: a Matter of 
 Life and DeathStemcells ( play a pivotal role in fueling homeostasis and r
 egeneration Whilemuch focus has been given to self renewal and differentia
 tion pathways regulatingSC fate\, little is known regarding the specific m
 echanisms utilized for theirelimination During my Ph D I determined that t
 he pro apoptotic protein ARTS(a Septin 4 isoform) is highly expressed in c
 ells comprising the intestinal SC (niche and that its deletion protects ce
 lls from undergoing apoptosis As a result\,the Sept 4 /ARTS crypt displays
  heightened proliferation and\, in culture\, generatesmassive cystic organ
 oids due to enhanced Wnt/β catenin signaling Importantly\, micedeleted fo
 r Sept 4 /ARTS exhibit resistance against intestinal damage in a mannerdep
 endent upon ISCs Finally\, I was able to show that ARTS interacts with XIA
 P inintestinal crypt cells and that deletion of XIAP can abrogate Sept 4 /
 ARTSdependent phenotypes in an epistatic manner (Koren et al Nature Commun
 ications\,2018 These results indicate that ISCs utilize specific apoptotic
  proteins for theirelimination representing a unique therapeutic targetCur
 rentlyI am testing distinct compounds that have been identified via highth
 roughput in vitro and in silico screening platforms\, for their potential 
 totherapeutically block the ARTS/ XIAP interface It is my greatest hope th
 at my findingsmay one day serve as a staple for human disease treatmentsIn
 the skin\, the presence of a distinct SC population that maintains the int
 erfollicularepidermis ( is highly debated We found that basal keratinocyte
 s marked by Thy 1do not express T cell markers\, express a unique transcri
 ptional profile\, cyclesignificantly slower than basal epidermal progenito
 rs and display significantexpansion potential in vitro Multicolor lineage 
 tracing analyses and mathematicalmodeling reveals that Thy 1 basal keratin
 ocytes do not compete neutrally alike IFEprogenitors and contribute long t
 erm to both epidermal replenishment and woundrepair Importantly\, ablation
  of Thy 1 cells in T cell deficient mice strongly impairsthese processes\,
  thus indicating the non redundant function of Thy 1 SCs in theepidermis T
 aken together\, these findings indicate the existence of a distinct slowcy
 cling SC population that plays a critical role in epidermal homeostasis an
 d 

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