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Gaetano Gargiulo, PhD - "Tumor homeostates revealed by synthetic locus control regions"

Molecular Oncology, Max-Delbrück-Center for Molecular Medicine (MDC), Berlin, Germany
When Feb 03, 2020
from 12:00 PM to 01:30 PM
Where Tigem, Auditorium Vesuvius
Contact Name
Contact Phone 08119230659
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Short CV

Our understanding of developmental and disease homeostasis requires genetic tracing to selectively identify cellular states and fate transitions without perturbing them. I will discuss a method we invented and developed to translate multifactorial signatures representing cellular states into synthetic genetic tracing cassettes. Using synthetic locus control regions (sLCRs), we investigated the cellular and  molecular basis underlying glioblastoma heterogeneity by genetically tracing tumor cells adopting similar states under homeostatic conditions in vitro and in vivo. Cell fate tracing by sLCRs demonstrates that the proneural glioblastoma is a hardwired identity. Instead, the mesenchymal glioblastoma is a metastable state downstream pro-inflammatory and differentiation cues, genetically- and pharmacologically-tunable and similarly wired in breast and lung tumors. Notably, we discovered that innate immune cells divert glioma cells into a specific mesenchymal  state causal to therapeutic resistance. I will show evidence that the same approach is potentially valid also to report on the cellular response to stress. Hence, this simple, automated and scalable strategy advances genetic tracing of intrinsic cell states, adaptive responses and pharmacogenomics in development and disease.

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