Dung-Fang Lee, Ph.D.
The University of Texas Health Science Center
The Epitranscriptomic Pathway is a Therapeutic Vulnerability in p53-mutant Osteosarcoma
Osteosarcoma is among the most frequent primary malignant bone cancers in childhood and adolescence. A scientist by training, Dr. Lee is studying a genetic mutation in the p53 tumor suppressor gene to help illuminate how it contributes to the development of osteosarcoma. A successful Powered by Pablove research project will aid greatly in diagnosis or treatment of this cancer, and provide insight into personalized osteosarcoma treatment.
In Dr. Lee’s own words:
Our laboratory is dedicated to understand cancer pathological mechanisms and identify new therapies for cancer treatment by using pluripotent stem cell (PSC) disease models. We focus on osteosarcoma, the most frequent primary malignant bone cancer of childhood and adolescence. Among osteosarcoma-associated pathological alterations, p53 tumor suppressor is commonly mutated in more than 50% of clinical OS specimens, highlighting the crucial role of p53 in preventing bone malignancy. Patients Li-Fraumeni syndrome (LFS), an inherited autosomal dominant cancer disorder caused by germline mutations/deletions in the p53 tumor suppressor gene, have a significantly increased incidence of osteosarcoma, providing a perfect disease platform to investigate how mutant p53 (mutp53) leads to osteosarcomagenesis. In our preliminary studies, we examined LFS PSCs and identified an increase of a key m6A regulator ALKBH5 in mutp53 osteoblasts. Using LFS PSC platform, we will investigate how mutp53 contributes to upregulated ALKBH5 and evaluate if ALKBH5 inhibitors are effective in killing mutp53 osteosarcoma. Our work if successful will have a broad impact on the field to understand the role of mutp53 in osteosarcomagenesis, greatly aid in diagnosis or treatment, and provide insight into personalized osteosarcoma treatment. In the long term, these studies will reveal novel therapeutic targets to treat multiple pediatric cancers with dysregulated p53 function.