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UID:951@biology.technion.ac.il

DTSTART;TZID=Asia/Jerusalem:20210420T143000

DTEND;TZID=Asia/Jerusalem:20210420T153000

DTSTAMP:20210802T125904Z

URL:https://biology.technion.ac.il/en/seminars/phd-graduate-seminar-boris-
 sarvin-2/

SUMMARY:PHD GRADUATE SEMINAR-BORIS SARVIN [No Categories]
DESCRIPTION:Location:   \n Affiliation: \n Host:\n Research Topic: Mass spe
 ctrometry approaches for studying cancermetabolism  Mass spectrometry bas
 ed metabolomics is a widely usedapproach in biomedical research. However\,
  current methods coupling massspectrometry with chromatography (LC-MS) are
  time-consuming and not suitablefor high-throughput analysis of thousands 
 of samples. In a paper recentlypublished in Nature Communications wedescri
 be an approach for high-throughput metabolomics based on flow-injectionmas
 s spectrometry (FI-MS) in which samples are directly injected to theioniza
 tion source. We show how MS overloading with this approach can be overcome
 by analyzing the distribution of ion m/z values and computationally determ
 ininga series of optimal scan ranges for getting highly reproducible data.
  In afollow up work\, we developed a sub one-minute LC-MS based metabolomi
 cs methodand demonstrate comparable analytical performance to a standard 2
 5 minutesLC-MS method. We are currently using these approaches as a basis 
 for developingearly diagnosis methods for the top-5 frequent cancers in Is
 rael basedthousands of serum samples obtained from Rambam Hospital. Anothe
 r focus of my research was developing a LC-MS basedmethod for investigatio
 n of one-carbon (1C) metabolism. Folate metabolism supplies 1C units for b
 iosynthesisand methylation and has long been a target for cancer chemother
 apy. In arecently published article in CellMetabolism we showed that while
  mitochondrial metabolism is considered themajor source of 1C units in can
 cer\, it is actually the cytosolic pathway that predominantlyproduce 1C un
 its in a variety of tumors under physiological conditions.Tumor-specific r
 eliance on cytosolic 1C flux is associated with poor capacityto retain int
 racellular folates\, which is determined by the expression of Reducedfolat
 e carrier (RFC1). We showed that silencing SHMT1 (cytosolic 1C producingen
 zyme) in cells with low RFC1 expression impairs pyrimidine biosynthesis an
 dtumor growth in vivo. Overall\, ourfindings reveal major diversity in can
 cer cell utilization of the cytosolicversus mitochondrial folate cycle acr
 oss tumors and RFC1 expression as a markerfor increased reliance on SHMT1.
  

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