Dung-Fang Lee
Associate Professor
The University of Texas Health Science Center at Houston
McGovern Medical School
Department of Integrative Biology and Pharmacology
Our research is dedicated to unraveling the enhanced functions of mutant p53, a protein implicated in the development of various cancers. By understanding how mutant p53 promotes cancer, we aim to identify potential strategies to counteract its oncogenic effects. Over the past few years, our investigations have yielded significant breakthroughs in comprehending the functions, mechanisms, and regulation of mutant p53. Our focus has been particularly pronounced in the context of Li-Fraumeni syndrome (LFS), a hereditary cancer syndrome linked to mutations in the TP53 tumor suppressor gene. To delve into the intricacies of mutant p53, we have harnessed the power of induced pluripotent stem cells (iPSCs) derived from individuals with LFS. These cells serve as invaluable tools for modeling and studying malignancies associated with mutant p53. Our approach involves dissecting gene expression profiles, unraveling cellular mechanisms (e.g., m6A epitranscriptome and MLL1 epigenome), and exploring tumor microenvironments, allowing us to develop compounds and gene-editing strategies aimed at reversing the aberrant transcriptomes characteristic of p53-mutant cancers. These insights pave the way for potential breakthroughs in future cancer treatments.
In addition, the RB1 tumor suppressor is inactivated through various mechanisms. Our research explores the connection between RB1 gene mutations and osteosarcomagenesis, with a particular focus on hereditary retinoblastoma (HRB), a genetic condition caused by autosomal dominant mutations in the RB1 gene. HRB patients face a significantly elevated risk of developing osteosarcoma. We have developed an HRB iPSC disease model that recapitulates the bone malignancy phenotype, enabling us to investigate the role of RB1 in regulating RNA splicing and genome architecture, as well as to explore potential therapeutic interventions.
Beyond mutant p53 and RB1, our research extends to investigating the tumor suppressor functions of other genes. Using corresponding genetic iPSC models for conditions such as Rothmund-Thomson syndrome, Noonan syndrome, and LEOPARD syndrome, we aim to broaden our understanding of various cancer predisposition syndromes. This comprehensive approach not only sheds light on the complexities of these syndromes but also holds promise for developing novel therapeutic interventions for a spectrum of hereditary cancers.
What students can learn during the tutorial: Our laboratory offers a comprehensive tutorial that provides hands-on experience in iPSC disease modeling and cancer genetics. Participants will gain proficiency in iPSC/hESC culture, tissue differentiation, TALEN/CRISPR genome editing, systems biology analysis, and cellular/molecular biology techniques essential for studying cancer pathogenesis. Additionally, the tutorial emphasizes the development of independent thinking and experimental design skills for addressing fundamental biomedical questions.
Education & Training
PhD, MD Anderson UTHealth Houston Graduate School, 2008