Research Overview
The majority of the human genome is transcribed into RNA that does not encode proteins. Among these transcripts, long non-coding RNAs (lncRNAs) have emerged as critical regulators of gene expression and cellular function, yet their molecular mechanisms remain incompletely understood. Our research aims to define lncRNA function across multiple scales — from molecular structure and RNA–protein interactions to cellular phenotypes and disease relevance. This work is inherently interdisciplinary, combining: Cell biology to study lncRNA function in living systems and disease models Biochemistry and structural approaches to characterize RNA structure and RNA–protein interactions Genomics and computational tools to analyze transcriptomes, identify functional RNA domains, and map regulatory networks Together, these approaches connect molecular mechanism with biological function.
Current Projects
Mechanisms of lncRNA-Mediated Gene Regulation
A major focus of our research is understanding how lncRNAs regulate transcription through interactions with chromatin-associated proteins. ​Recently, we demonstrated that the cancer-associated lncRNA lncTCF7 promotes activation of WNT signaling by recruiting the RNA-binding protein SND1 and chromatin-remodeling complexes to the TCF7 locus. We further mapped functional RNA domains required for protein binding and transcriptional activation.​ This work supports a model in which lncRNAs function as molecular scaffolds that assemble gene-regulatory protein complexes at specific genomic locations.
Tissue-Specific lncRNAs in Physiology and Disease
Many lncRNAs exhibit strong tissue-specific expression, suggesting specialized roles in tissue function and disease. Our work investigates tissue-enriched lncRNAs and their roles in cancer and viral infection. For example, we identified the tissue-specific lncRNA FAM99A as a tumor suppressor that interacts with the protein-translation machinery and suppresses global protein synthesis. This work expands the functional repertoire of lncRNAs beyond transcriptional regulation to include control of protein translation. These studies are conducted in collaboration with clinical and basic science partners across multiple biological systems.
RNA Structure–Function Relationships
LncRNAs often show limited sequence conservation but retain conserved secondary and tertiary structural features. Understanding how RNA structure determines function is a central theme of the laboratory. Our work has shown that: a) Conserved structural elements exist within lncRNAs despite sequence divergence b) Distinct structural domains are required for the oncogenic activity of the prostate cancer lncRNA SChLAP1 These findings demonstrate that RNA structure is a key determinant of lncRNA function and highlight the importance of combining biochemical, structural, and computational approaches.