Ron J. Leavitt (Switzerland)
CHUV/UNIL
Radiation Oncology Service/ Department of Oncology
I am a postdoctoral researcher in the laboratory of Dr. Marie-Catherine Vozenin at the CHUV in Lausanne, Switzerland, where I have the opportunity to work on cutting-edge FLASH radiotherapy (RT). In 2020 I earned a Ph.D. in Environmental Health Sciences at the University of California, Irvine (UCI) under Dr. Charles Limoli, having studied the mitigation of RT-associated cognitive dysfunction using extracellular vesicles (EV) derived from neural stem cells and the mechanism involved. The work in the Limoli lab combined my interest in epigenetics and the “nature vs. nurture” question with the subject of environmental toxicology and growing importance of the issue of how environmental exposures affect health and disease. A question with ever more importance as the world becomes more interconnected and the incidence of cancer rising. It is imperative that the treatment of diseases like cancer do not leave patients so burdened that they are unable to enjoy life after treatment. A common thread throughout both my doctoral and postdoctoral work has been the mitigation of normal tissue damage surrounding RT.

Moderator of 1 Session

 Online Program
Proton Beam and Heavy Ions

Proton Beam and Heavy Ions: High Dose Rate p, 4He and 12C Ion Therapy: Biological Investigations at Heidelberg Ion-Beam Therapy Center (HIT)

Session Type
Proton Beam and Heavy Ions
Date
02.12.2022
Session Time
15:40 - 16:10
Room
Hall 113-114
Chair(s)

Presenter of 1 Presentation

 Online Program

MIR-124-3P EXPRESSION IS PRESERVED AFTER FLASH-RT

Session Type
FLASH Mechanisms Track
Session Name
0190 - FLASH Mechanisms : In Vivo (Part I) - (Oral presentations) (ID 8)
Date
30.11.2022
Session Time
11:00 - 12:00
Room
Hall 133-134
Presenter
Lecture Time
11:09 - 11:18

Abstract

Background and Aims

We previously identified the micro-RNA (miRNA), miR-124-3p, as a neuroprotective miRNA present in the bioactive cargo of extracellular vesicles able to counteract delayed radiation-injury in the brain (1). miR-124-3p promotes M2 polarization of microglia simultaneously reducing neuroinflammation and promoting neurogenesis. The present study was undertaken to investigate whether miR-124-3p could also be involved in neuroprotection following FLASH-RT.

Methods

Tumor-free female pediatric mice (n = 5 per group; 3 weeks old, at time of weaning) were irradiated in a single-dose regimen with 8 Gy of 6 MeV electrons administered at ultra-high dose rates (UHDR, 1 pulse, 100 Hz, 1.8 µs pulse width) or at conventional dose rates (CONV, ~ 0.1-0.2 Gy/s) with the Oriatron/eRT6 (PMB-Alcen, FR). Following comprehensive behavioral testing at 2- and 4-months post-IR (reported previously, (2)), brains were sampled, micro-dissected and flash-frozen in liquid nitrogen. Total RNA was extracted, and miR-124-3p levels were evaluated using the TaqMan Advanced miRNA Assay (ThermoFisher).

Results

Results showed that bulk brain expression of regenerative, anti-inflammatory miR-124-3p is high and at near-control levels at late time points (5 months) post-FLASH-RT, whereas miR-124-3p levels were found to be decreased significantly after CONV-RT.

Conclusions

We are in the process of analyzing more acute timepoints (< 1 mo post-irradiation) and in adult mice to investigate whether preservation of miR-124-3p levels could be used as an early marker of the sparing efficacy of FLASH-RT.

Acknowledgement: The study is funded by SNF Synergia grant (FNS CRS II5_186369)

1. R. J. Leavitt, M. M. Acharya, J. E. Baulch, C. L. Limoli, Extracellular Vesicle–Derived miR-124 Resolves Radiation-Induced Brain Injury. Cancer Research 80, 4266–4277 (2020).

2. Y. Alaghband, et al., Neuroprotection of Radiosensitive Juvenile Mice by Ultra-High Dose Rate FLASH Irradiation. Cancers (Basel) 12 (2020).

Hide