Project Details
Projekt
Molecular Exploitation of Amyloid Precursor Protein as Novel Ferroptosis Regulator
Applicant
Privatdozent Dr. Vivek Venkataramani
Subject Area
Cell Biology
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 461705388
Ferroptosis, an iron-dependent form of cell demise, is pivotal in aggressive cancers like castration-resistant prostate cancer (CRPC) and neurodegenerative conditions. Our previous research has identified the Alzheimer’s amyloid precursor protein (APP) as a central player in CRPC, governing resistance to ferroptosis by regulating heme oxygenase-1 (HO-1) and the heme-dependent transcription factor BTB and CNC homology 1 (BACH1). This proposal aims to explore APP's role in ferroptosis and its broader impact on cellular metabolism in CRPC. Leveraging advanced methodologies such as CRISPR-Cas9 screening and patient-derived organoid (PDO) models, we aim to uncover the intricate molecular mechanisms governing ferroptosis. Additionally, we will conduct a DNA-encoded library (DEL) screen to identify novel compounds targeting APP and modulating ferroptosis. Utilizing our developed CE-ICP-MS technique for precise quantification of iron species, our goal is to gain crucial insights into iron metabolism and its impact on ferroptosis regulation. Our objectives include elucidating the influence of APP on ferroptosis, validating ferroptosis-related targets in CRPC through PDO models, and identifying novel compounds targeting APP to modulate ferroptosis. Through a comprehensive strategy integrating genetic screenings, pathway analyses, and drug discovery initiatives, we aim to uncover fresh therapeutic avenues to combat therapy-resistant CRPC.
DFG Programme
Priority Programmes
