Orlando Scharer

Summary

I am interested in further advancing our research and leveraging our findings for precision oncology. The HCC provides an ideal interdisciplinary environment for these efforts. 

I am focused on the below research areas:

1. Molecular mechanisms of human nucleotide excision repair (NER)
• Biochemical, cellular, structural and single molecule studies of damage recognition, complex assembly and dual incision in NER
• Determining the activity of NER proteins on DNA adducts formed by antitumor agents
• Development of new assays for monitoring NER activity in biochemical and cellular systems
• Elucidation of the molecular basis of phenotypes induced by mutations in NER genes in human patients

2. Trabectedin and lurbinectedin: new tool compounds for precision oncology
• Elucidation of the mechanisms by which trabectedin and lurbinectedin kill cancer cells in a DNA repair dependent manner
• Determine the genomic location of trabectedin and lurbinectedin induced breaks at a genome wide level
• Study the response of sarcoma, small cell lung and ovarian cancers to trabectedin and lurbinectedin

3. Platinum cancer therapy: Mechanisms of resistance and tools to predict clinical response
• Develop methods for the determination of cisplatin, oxaliplatin and carboplatin DNA adducts in cells using an UPLC-MS approach
• Develop approaches to map DNA repair incision at cisplatin, oxaliplatin and carboplatin DNA adducts at a genome-wide level
• Investigation of DNA repair pathways that contribute to resistance to platinum therapy in tumors