CRISPR Synthetic Lethality screens and TRANSFAC Pathways

Q&A: Coffee break with TRANSFAC

In this webinar Prof. Dr. Alexander Kel, the CEO and CSO of geneXplain GmbH, will address the in-depth exploration of how CRISPR gene knockouts can be leveraged for TRANSFAC pathway discovery and the identification of cancer master regulators within the TRANSFAC network.

This seminar will highlight the utility of CRISPR synthetic lethality screens in discovering drug targets and understanding disease mechanisms within TRANSFAC pathways. Alexander will showcase a case study where a synthetic lethal CRISPR screen identified a cancer cell-intrinsic role of PD-L1 in regulating vulnerability to ferroptosis in Homo sapiens (GSE268533). Despite the success of PD-1/PD-L1 inhibitors in cancer therapy, only a minority of patients benefit from these treatments. The presented study uses a genome-wide CRISPR screen to explore the intrinsic function of PD-L1 in head and neck squamous cell carcinoma (HNSCC). This seminar will focus on how synthetic lethality screens, combined with the TRANSFAC database, can uncover pathways and regulatory mechanisms that highlight PD-L1’s role in cancer resilience. Additionally, we’ll discuss how these insights can enhance therapeutic strategies by targeting intrinsic PD-L1 functions. The following main questions will be in the focus of this seminar:

• Genome-wide CRISPR/Cas-9 synthetic lethality screens to discover anti-cancer drug targets
• Analysis of GSE268533 dataset of head and neck squamous cell carcinoma (HNSCC)
• Mapping the results of CRISPR/Cas-9 synthetic lethality screens on TRANSFAC pathways
• Finding master-regulators to resolve resistance to PD-L1 inhibitors