Research Focus Area
Our research program aims to uncover the hidden role of the “dark genome”—the 50-70% of genomic human DNA previously considered non-functional—in cancer development and treatment. Specifically, it focuses on expressed human retro-transposable elements (EREs), a class of repetitive non-coding DNA sequences such as LINE-1 (L1), Alu/SINE, and human endogenous retroviruses (HERVs), which are typically silenced in healthy tissues but become abnormally activated in many cancers and age-related diseases. The objectives of the lab’s research program are to:
- Determine whether EREs are over-expressed in precancerous tissues and contribute to cancer initiation.
- Investigate whether inhibiting ERE-encoded reverse transcriptase (RT) can prevent tumor formation.
- Explore the potential of ERE-derived proteins and expressed open-reading frames as novel targets for cancer immunotherapy.
- Assess whether ERE nucleic acids and peptides in extracellular vesicles (EVs) in blood plasma can serve as biomarkers for early cancer detection and treatment monitoring and develop high-throughput lab-on-a-chip detection methods for EREs as new cancer diagnostics.
The research approach integrates molecular biology, genomics, immunology, and translational biotherapeutics. The lab analyzes ERE expression patterns in various cancer types, study their impact on DNA damage and inflammation, and evaluates their immunogenic potential. The program also aims to develop innovative diagnostic tools and therapeutic strategies targeting EREs, particularly for hard-to-treat cancers such as pancreatic cancer, bile duct cancers, and brain cancer. A key approach used in the lab is the study of EVs that serve as local and long-distance “molecular messengers” in the body. These EVs are released from the cells in our body and circulate in our blood. Tumour cells especially release copious amounts of EVs that contain nucleic acid signatures and proteins from EREs and other genomic elements that serve as “fingerprints” of what are expressed in tumours. As such, EVs can serve as powerful biomarkers in blood that can be readily isolated for screening novel ERE antigens for immunotherapy (cancer vaccine development) and biomarkers for early cancer detection and monitoring disease recurrence, both key aims of the research program. For this aspect, the lab is also collaborating with bioengineers and physicists to develop novel ERE detection methods in EVs such as a new nanomolar-sensitive microfluidics-based surface-enhanced Raman spectroscopy (SERS) approach.
This work in the lab on EREs is highly significant because it helps shifts the paradigm of cancer research beyond traditional protein-coding genes to explore the vast, uncharted territory of the non-coding genome previously ignored for decades. By investigating how EREs contribute to tumor development and immune activation or immune dysfunction in cancer, the program could lead to groundbreaking therapies and early detection methods for cancers that currently lack effective treatments. Ultimately, this research has the potential to transform our understanding of cancer biology and open new avenues for precision medicine.