Whitney Nolte, PhD, Clinical Pharmacology and Toxicology, Irina Pushel, PhD, Genomic Medicine Center, and Atul Ranjan, PhD, Research Scientist, Division of Hematology & Oncology, were all recipients of Partners Advisory Board funding from the Masonic Cancer Alliance, the outreach network of The University of Kansas Cancer Center.
Dr. Nolte will use her two-year, $244,109 funding for her project, “Stability Proteomics Methods to Identify Targets of a Potential Anti-Cancer Drug.” Dr. Pushel will use her two-year, $250,000 funding for her project, “Multi-omic Profiling of Pediatric Leukemias.” Both of their project periods run from Dec. 1, 2022 through Nov. 30, 2024. Dr. Ranjan’s two-year, $249,999 grant goes to his study “The p53-dependent and independent roles of RUNDC1 in sarcoma progression,” with a project period of Dec. 1, 2021 through Dec. 31, 2023.
Dr. Nolte’s project focuses on osteosarcoma, a common and deadly form of cancer in pediatric populations.
“Previously, we used a high-throughput screen to identify a set of compounds that can specifically kill p53-deficient osteosarcoma cells. Our current approach is to use stability proteomics methods to identify the protein targets of these compounds, as well as to establish an affordable and feasible system to identify target proteins of any compound at Children’s Mercy Research Institute,” said Dr. Nolte.
Proteomics is the large-scale study of proteins, their structure and physiological role or functions. Dr. Nolte explains that understanding the mechanism of action of these compounds that target osteosarcoma cells will potentially enable her and her study team to improve the efficacy of the compounds and develop novel anti-cancer therapeutics.
Dr. Pushel’s project looks to expand beyond looking at a patient’s DNA to help with treatment for a child with leukemia.
“While this current method has advanced our understanding of childhood cancers and improved outcomes for patients, in many cases this approach is very limited,” said Dr. Pushel.
Dr. Pushel and her study team will extend this method to include additional data about a patient’s RNA and protein expression, which give a clearer picture of what may be driving a particular cancer and which treatments may be effective against it.
“In the future, these multi-dimensional classifications of leukemias will allow us to better characterize and more effectively treat children with leukemia,” said Dr. Pushel.
Dr. Ranjan’s study will give mechanistic insight of RUNDC1’s role in sarcoma in both p53-dependent and -independent manners. They are investigating the hypothesis that RUNDC1 plays a role in cancer progression or suppression as well as its role in potentially regulating p53 activity.
Sarcoma is a type of cancer that can develop in children, adolescents, and young adults, accounting for approximately 15 percent of all childhood cancers. Using osteosarcoma cells, Dr. Ranjan and his team identified RUNDC1 protein as a regulator of tumor suppressor p53’s activity. High levels of RUNDC1 (RUN domain containing protein 1) in sarcoma are correlated with better overall patient survival.
When the study is completed, the team hopes to be able to identify changes in genes and pathways altered by RUNDC1 and reveal the RUNDC1 interactome (set of molecular interactions in a particular cell).
“This will ultimately help identify novel therapeutic targets for osteosarcoma and other types of cancer, which will have a significant impact on the prognosis of patients with pediatric sarcomas,” he said.