Ramiro Martinez

Immune checkpoint therapies (ICTs) have revolutionized cancer treatment by harnessing the power of the immune system, yet many patients experience limited responses and eventual relapse. Our research seeks to unravel the complex mechanisms underlying tumor immune evasion, with a particular focus on the emerging role of long non-coding RNAs (lncRNAs) in modulating T-cell activation and tumor cell interactions. Recognizing that lncRNAs may serve as pivotal regulators of immune responses, our current project integrates advanced cellular models and innovative genetic screening techniques to identify novel immuno-modulatory targets. We utilize a Jurkat-derived cell line engineered to express a GFP reporter driven by an NFAT promoter, alongside a MART-1-specific T-cell receptor, to monitor immune activation in real time. In parallel, both our T-cell and melanoma cell models have been modified with a dCas9-KRAB-MECP2 system, enabling precise CRISPR interference with a custom sgRNA library targeting highly expressed lncRNAs. Through pooled screening in co-culture systems with the melanoma cell line MALME3M, we are systematically uncovering lncRNA candidates that may influence the efficacy of ICTs. Complementing our genetic approach, we have developed a high-throughput lentiviral-based platform to silence both lncRNAs and protein-coding genes in melanoma cells, and initiated a compound screening program involving over 3,000 molecules to identify agents that enhance T-cell and tumor cell interactions. By bridging molecular insights with therapeutic innovation, our work aims to extend the benefits of ICTs and ultimately improve clinical outcomes across a broad spectrum of cancers.
 

• Lab address: 
  - Postal and laboratory address: Medical Research Building 1 (MRB1, entrance 34)
  - Office address: The Core, third floor, room 130.006 (entrance 37a)
• Ramiro Martinez is interested to receive invitations for presentations or talks