Dr Benjamin Housden
Research Fellow (LSI)
01392 72 7475
Living Systems Institute T04.13
I began my research career in the laboratory of Dr. Sarah Bray at the University of Cambridge. There, I studied the direct transcriptional outputs of Notch signaling and crosstalk with the EGFR pathway using Drosophila as a model system. From this work, I gained valuable experience working with transcriptomics datasets and developed an appreciation of the network-like organization of signaling pathways. In addition, I realized the advantages of using model organisms such as Drosophila to tease apart the mechanisms of complex systems relevant to mammalian models and humans.
For my postdoctoral work, I joined Dr. Norbert Perrimon’s laboratory at Harvard Medical School. Here, my interest in signaling networks led me to develop combinatorial screening methods to identify synthetic lethal interactions in a high-throughput manner. A synthetic lethal interaction is a relationship between two genes where simultaneous disruption of both is lethal but disruption of either gene alone is not. Knowledge of synthetic lethal interactions has many applications, including mapping of signaling networks, determining the functions of individual network components and identifying drug targets for human disease. However, while synthetic lethal interaction maps have been generated for single celled organisms such as yeast, methods that allow robust and systematic mapping of synthetic lethal interactions in multicellular models are currently lacking. I therefore focused on developing improved methods to identify synthetic lethal interactions using Drosophila as a model organism.
I am now establishing my research group at the Living Systems Institute. Here, we will use the screening methods that I developed in my postdoc to identify new therapeutic drugs for a range of tumourigenic diseases and improve our understanding of the mechanisms underlying tumour formation.
My group is focused on using synthetic lethal interaction screening to identify candidate drug targets for human diseases. In particular, we are investigating tuberous sclerosis complex (TSC) disease, which is caused by mutation of either the TSC1 or TSC2 genes and results in the formation of tumours in a wide range of tissues. In addition, we are now expanding our efforts to identify candidate drugs for other tumourigenic diseases including neurofibromatosis (NF).
To identify drug targets, we use a combination of high-throughput RNAi screening in Drosophila cells followed by validation experiments in mouse and human cells to determine the most promising drugs. In addition, we are developing new screening technologies to improve the speed with which synthetic lethal interactions can be mapped.
- Repurposing clinically approved drugs for the treatment of Tuberous Sclerosis Complex (TSC)
- Using synthetic lethal screens to identify drug targets for neurofibromatosis type 1
- Development of improved technologies for high-throughput RNAi screening
- 2018 DoD/TSCRP
DoD/TSCRP: A unique opportunity for TSC: Repurposing FDA approved drugs using a unique combinatorial screening strategy. July 2016 - July 2018.