|Awarded On||May 18, 2022|
|Title||Recruitment of First-Time, Tenure-Track Faculty Members|
|Award Mechanism||Recruitment of First-Time, Tenure-Track Faculty Members|
|Principal Investigator/Program Director||Jonathan Clinger|
|Cancer Sites||All Sites|
|Summary of Goals and Objectives||
This proposal utilizes time-resolved and multi-temperature crystallography of polyamine biosynthesis enzymes: ornithine decarboxylase (ODC), spermidine synthase (SPDS), and spermine synthase (SPS) to improve the structural knowledgebase of these enzymes for dynamic structure-based inhibitor design. These enzymes are upregulated in aggressive hepatocellular carcinomas and in childhood neuroblastomas, and ODC provides feedback to the oncogene myc. However, only ODC has an FDA approved inhibitor, and high-throughput inhibitor screening of these enzymes has proven challenging due to the lack of development of applicable assays. Time-resolved crystallography, utilizing the recently developed Mill...