Isaac Fianu

Assistant: Andy Lo

Every cell in our body contains nearly identical genetic information (DNA), which is carefully maintained and passed on. However, only a small subset of our genes is active at any given time and location in our body. The processes that control when and where genes are turned on play a crucial role in how our bodies develop and how cells respond to various situations. We use biochemistry, structural biology—especially cryo-electron microscopy—and other methods to study these processes in health and disease states.

How gene activity is controlled: RNA Polymerase II (Pol II) transcribes majority of our genes and it is regulated by factors that either increase or decrease RNA synthesis. In complex organisms like humans, gene regulation involves premature Pol II termination which is done by the large molecular complex called Integrator. Mutations in Integrator subunits are associated with various diseases, including developmental disorders, neurodegenerative conditions, and cancers, highlighting the importance of this process. Our research focuses on understanding how premature Pol II termination works in different contexts, with particular emphasis on the Integrator complex.

Gene activity and genome stability: The machineries responsible for gene transcription, DNA replication and repair must smoothly navigate the DNA strands of our genome. Lack of coordination between these processes leads to conflicts that stress cells and potentially cause genome instability. We are interested in understanding the basic principles of coordination between these processes, and how conflicts between them are recognized and resolved.

We hope to provide a deeper understanding of the spatiotemporal control of gene activity and elucidate fundamental mechanisms of systems coordination between transcription, DNA replication and repair. This knowledge could potentially lead to new therapeutic approaches with broad applications.

We are currently seeking new team members at all levels. If you are interested in a postdoctoral position, please email Isaac directly. For graduate student opportunities, kindly apply through one of our graduate programs.

Email: [email protected]
X: @isaac_fianu