The focus of my laboratory is to understand how SDRT can initiate an innate response in the local tumor and also contribute to initiation of a response in distant tumors (Abscopal/Adscopal like effects).
In addition, we use combination of SDRT and chemotherapeutic drugs with short acting anti-angiogenic agents, which result in improved tumor response with less overall toxicity.
Adriana Haimovitz-Friedman, PhD
Research FocusOptimizing the use of Single high Dose Radiation Therapy (SDRT) in pre-clinical studies to activate innate immune signaling pathways, potentially leading to adaptive immune responses within the local tumors and in distant ones, i.e eliciting Adscopal and/or Abscopal effects.
- Wang F, Li H, Markovsky E, Glass R, de Stanchina E, Powell SN, Schwartz GK, Haimovitz-Friedman A. Pazopanib radio-sensitization of human sarcoma tumors. Oncotarget. 2018 Feb 6;9(10):9311. doi: 10.18632/oncotarget.24281. eCollection 2018 Feb 6.
- van Hell AJ, Haimovitz-Friedman A, Fuks Z, Tap WD, Kolesnick R. Gemcitabine kills proliferating endothelial cells exclusively via acid sphingomyelinase activation. Cell Signal. 2017 Feb 24; 34:86-91. doi: 10.1016/j.cellsig.2017.02.021. [Epub ahead of print] PMID: 28238856. DOI: 10.1016/j.cellsig.2017.02.021
- Our Laboratory was the first to discover that radiation can induced damage to the plasma membrane of the endothelial cells, which resulted in a paradigm shift in the treatments of radiation and introduced the Single high Dose Radiation therapy, SDRT, in the clinic, which results in cures for those tumors that are otherwise non-responders to conventional fractionated radiation therapy.
- We found the optimal timing to combine SDRT with anti-angiogenics and with chemotherapy.
- For both prostate and breast cancers, ATM down regulation can radiosensitize via a specific signal transduction pathway involving de novo ceramide generation.
- Radiation-induced acute blood-brain barrier disruption is mediated by the acid sphingomyelinase (ASMase) pathway, a major contribution to the radiation and brain drug delivery field.
- Mice suffering from sepsis can be rescued by protecting the microvasculature.
- Mice are protected from Radiation-induced gastrointestinal syndrome by protecting the microvasculature via inhibition of the ASMase/Ceramide pathway.