Our Research focuses on 3 main areas of investigation:
1. Molecular Mechanisms of Telomerase RNP Assembly and Regulation
This project investigates the molecular assembly, structural dynamics, and regulation of the native telomerase ribonucleoprotein (RNP) complex in the parasitic protist Trypanosoma brucei. We focus on how specific structural domains of telomerase RNA (TbTR) mediate TERT recruitment, catalytic RNP assembly, and interactions with accessory proteins. By combining RNA structure probing with biochemical and functional analyses, we examine the RNA structural rearrangements that accompany the transition from free TbTR to the assembled, catalytically active telomerase RNP. These studies aim to define how RNA conformational dynamics and RNA–protein interactions regulate telomerase activity and identify fundamental principles governing the assembly of this essential RNP enzyme.
Collaborators: Dr. Bibo Li (Cleveland State University), Dr. Alain Laederach (UNC Chapel Hill) and Dr. Andrew Truman (UNC Charlotte), Dr. Abhishek Dey (NIPER, India)
2. RNA secondary structures, m6A modifications and RNA 3′ end processing
This project investigates how mRNA epitranscriptomic modifications and RNA structure regulate gene expression in the human malaria parasite Plasmodium falciparum. We focus on defining the transcriptome-wide distribution and dynamics of N6-methyladenosine (m6A) and determining how m6A is associated with local RNA structural features, transcript stability, and 3′-end processing/alternative polyadenylation. By integrating nucleotide-resolution m6A mapping, Nanopore direct RNA sequencing, RNA structure analysis, and functional studies of the parasite m6A machinery, we aim to uncover how the interplay between RNA modification, structure, and processing shapes parasite gene regulation and adaptation to environmental and drug-induced stress.
Collaborators: Dr. Kate Meyer (Duke University), Dr. Arthur Hunt, University of Kentucky, Dr. Christoph Dietrich, Heidelberg University, Dr. Shaoyu Li, UNC Charlotte, Dr. Sarath Chandra Janga (Indiana Univ-Purdue University, IN) and Dr. Robert Reid, UNC Charlotte.
3. Human DBR1 as a Regulator of mRNA Fate: From Splicing to Surveillance and Stress Granules
This project investigates the emerging roles of human DBR1 in coordinating post-transcriptional mRNA fate beyond its canonical function in RNA lariat debranching. We examine how DBR1 influences alternative splicing and mRNA surveillance pathways, including nonsense-mediated mRNA decay (NMD), through its interactions with key RNA-processing factors. We further investigate the role of DBR1 in cellular stress responses and stress-granule dynamics, with the goal of defining how DBR1 integrates RNA processing, quality control, and cytoplasmic RNA localization to determine the fate of cellular mRNAs.
Collaborators: Dr. Guramrit Singh (Ohio State University), Dr. Andrew Truman, UNC Charlotte, Dr. Didier Dreau, UNC Charlotte