Vihandha Wickramasinghe lab

Messenger RNA (or mRNA) is part of the central dogma of biology. RNA is enjoying a renaissance in both biology and medicine due to the efficacy of mRNA based therapeutics in treating COVID and holds tremendous promise for treating many diseases, including cancer. At the Vihandha Wickramasinghe lab, we aim to be at the forefront of this exciting time in RNA research. Visit Nature Reviews Cancer: RNA in Cancer for an overview. Through leveraging our curiosity driven work on export of mRNA from the nucleus and circular RNA to develop new RNA targeting therapies to treat cancer.

Current projects

New RNA-targeting therapeutics to treat cancer

A critical step in the gene expression pathway that is altered in cancer is nuclear export of messenger RNA (mRNA). We have demonstrated that mRNA export is not constitutive, but highly selective and can regulate distinct biological processes through poorly understood mechanisms.

The extraordinary success of RNA based therapeutics to treat COVID-19 has dramatically increased interest in other types of RNA targeting therapies. We have developed a completely new mRNA targeting therapy that works in the nucleus of cells and has the potential to be an exciting new frontier in cancer therapeutics. We are using cutting-edge cell biology, molecular biology and genetic approaches to understand how RNA export is altered in cancer and how our novel first-in-class inhibitors can be used to treat cancer.

Uncovering the promise of circular RNA in next generation RNA based therapeutics

RNA stability is a key determinant in improving the efficacy of RNA based therapeutics. Through our pioneering work on nuclear export of RNA over the past 15 years, we have uncovered key mechanisms that modulate RNA export and the stability of RNA in the nucleus and the cytoplasm. Many of these proteins are amplified in various types of cancer, underlying the importance of this cellular process in both fundamental RNA biology and in disease.

Recently, we have applied these principles to work out how circular RNAs, a subtype of RNA with great therapeutic potential, are exported from the nucleus. This work has uncovered a completely new mechanism for export that is distinct from export of mature mRNA. Our findings have important implications for the potential use of circular RNAs in therapeutics. We aim to make further advances in how biogenesis of circular RNAs is coupled to their export and stability, and be at the forefront in determining how circRNAs may play a role in the next generation of RNA based therapeutics.

Uncovering new links between the cell cycle, DNA damage and mRNA export that drive cancer

Nuclear export of messenger (mRNA) is extensively connected to transcription and processing of mRNA throughout the cell cycle. Little is known about how cancer cells regulate mRNA export during DNA replication. We have unexpectedly discovered that cell cycle regulated proteins regulate mRNA export during the DNA damage response in S-phase of the cell cycle.

We are using cutting-edge cell, molecular biology and genetic approaches to understand why these biological processes are linked and how they drive cancer. As several promising cancer therapies target these cellular pathways, this will reveal new cancer sub-types that may be suitable for treatment.

Current projects

New RNA-targeting therapeutics to treat cancer

Uncovering the promise of circular RNA in next generation RNA based therapeutics

Uncovering new links between the cell cycle, DNA damage and mRNA export that drive cancer

Related links

Related pages