Anastasia Velalopoulou (United States of America)
University of Pennsylvania
Department of Radiation Oncology
Anastasia Velalopoulou is a Research Associate in the Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania. Born and raised in Tinos island located in the Aegean Sea, in Greece, Anastasia received her B.Sc. (with a recognized integrated M.Sc.) in 2008, from the Department of Biological Applications and Technology of the University of Ioannina, Greece. In 2013, she earned her Ph.D. in Physiology, from the School of Medicine of the same University. Anastasia continued with her postdoctoral studies in the United States and the University of Pennsylvania and joined the field of FLASH radiotherapy in 2019, while jointly working in the labs of Constantinos Koumenis and Theresa Busch. In 2021, she reported the sparing properties of proton FLASH radiotherapy of the epithelial and mesenchymal tissues of the murine limb in the context of a sarcoma tumor. Her research efforts now focus on the elucidation of the underlying mechanisms of FLASH proton radiotherapy in various models of acute and chronic normal tissue toxicities

Moderator of 1 Session

 Online Program
FLASH Mechanisms Track

FLASH Mechanisms: Lipids Peroxidation in Liposomes after FLASH and CONV Irradiation

Session Type
FLASH Mechanisms Track
Date
30.11.2022
Session Time
10:00 - 10:30
Room
Hall 113-114
Chair(s)

Presenter of 1 Presentation

 Online Program

A TRANSCRIPTOMIC ATLAS OF THE MOUSE SKIN IRRADIATED WITH FLASH PROTON RADIATION

Session Type
FLASH Mechanisms Track
Session Name
0440 - FLASH Mechanisms : In Vivo (Part II) - (Oral Presentation) (ID 31)
Date
30.11.2022
Session Time
17:40 - 18:40
Room
Hall 129-130
Presenter
Lecture Time
18:07 - 18:16

Abstract

Background and Aims

Background: FLASH proton radiotherapy is evidenced to alleviate radiation-related toxicities in normal skin tissue compared to Standard radiotherapy. Aim: To investigate the transcriptomic changes induced by FLASH proton radiotherapy (F-PRT) that could be responsible for the protection of normal epithelial tissues by radiation-induced toxicities as have been previously shown by us and others.

Methods

Methods: C57BL/6J mice received 30 Gy of F-PRT or S-PRT to the hind leg at respective dose rates of 69-124 Gy/sec or 0.39–0.65 Gy/sec. RNA sequencing was performed using full-thickness leg skin at 5 days after radiation revealing major pathways regulated by F-PRT and S-PRT. In an endeavor to identify the full repertoire of cells and gene expression profiles that are involved in the sparing effects of FLASH PRT, we expanded our studies to include single-cell RNA sequencing (sc-RNA seq) and examined additional time points such as Day 2 and Day 10 after radiation. Single-cell transcriptome libraries were generated on a 10X Genomics Chromium system. Datasets were acquired from cell samples derived and sequenced from pooled skin samples of three mice per group. Skin from the sequenced mice was also embedded for spatial analysis of gene expression.

Results

Results: RNA sequencing revealed that F-PRT uniquely upregulates almost four times more genes compared to S-PRT (F-PRT-uniquely upregulated 489 genes vs S-PRT-uniquely upregulated 129 genes). Also, F-PRT uniquely downregulated 178 genes, compared to the 125 genes uniquely downregulated by S-PRT. GO analysis demonstrates that the keratinization and apoptosis pathways are uniquely upregulated by S-PRT, whereas F-PRT uniquely upregulates genes involved in vascular development pathway. During submission of the abstract, analysis of sc-RNA seq samples was pending.

Conclusions

Conclusion: Our comprehensive studies inform on the transcriptomic profiling of skin cell populations that are affected by F-PRT vs S-PRT; this insight will further spur discoveries on the biology of FLASH radiotherapy effects.

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