Loading content
Dr Benjamin Housden

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.

 

Qualifications

  • BA
  • MA
  • PhD

Research

Research interests

 

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.

 

Research projects

  • 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

Research grants

  • 2018 DoD/TSCRP
    DoD/TSCRP: A unique opportunity for TSC: Repurposing FDA approved drugs using a unique combinatorial screening strategy. July 2016 - July 2018.

Key publications | Publications by category | Publications by year

Publications by category


Journal articles

Housden BE, Muhar M, Gemberling M, Gersbach CA, Stainier DYR, Seydoux G, Mohr SE, Zuber J, Perrimon N (2017). Loss-of-function genetic tools for animal models: cross-species and cross-platform differences. Nat Rev Genet, 18(1), 24-40. Abstract.
Housden B, Nicholson H, Perrimon N (2017). Synthetic Lethality Screens Using RNAi in Combination with CRISPR-based Knockout in Drosophila Cells. BIO-PROTOCOL, 7(3).
Mohr SE, Hu Y, Ewen-Campen B, Housden BE, Viswanatha R, Perrimon N (2016). CRISPR guide RNA design for research applications. FEBS J, 283(17), 3232-3238. Abstract.  Author URL.
Housden BE, Perrimon N (2016). Cas9-Mediated Genome Engineering in Drosophila melanogaster. Cold Spring Harb Protoc, 2016(9). Abstract.  Author URL.
Housden BE, Perrimon N (2016). Comparing CRISPR and RNAi-based screening technologies. Nat Biotechnol, 34(6), 621-623. Author URL.
Chavez A, Tuttle M, Pruitt BW, Ewen-Campen B, Chari R, Ter-Ovanesyan D, Haque SJ, Cecchi RJ, Kowal EJK, Buchthal J, et al (2016). Comparison of Cas9 activators in multiple species. Nat Methods, 13(7), 563-567. Abstract.  Author URL.
Housden BE, Perrimon N (2016). Design and Generation of Donor Constructs for Genome Engineering in Drosophila. Cold Spring Harb Protoc, 2016(9). Abstract.  Author URL.
Housden BE, Hu Y, Perrimon N (2016). Design and Generation of Drosophila Single Guide RNA Expression Constructs. Cold Spring Harb Protoc, 2016(9). Abstract.  Author URL.
Housden BE, Perrimon N (2016). Detection of Indel Mutations in Drosophila by High-Resolution Melt Analysis (HRMA). Cold Spring Harb Protoc, 2016(9). Abstract.  Author URL.
Zacharioudaki E, Housden BE, Garinis G, Stojnic R, Delidakis C, Bray SJ (2016). Genes implicated in stem cell identity and temporal programme are directly targeted by Notch in neuroblast tumours. Development, 143(2), 219-231. Abstract.  Author URL.
Ammeux N, Housden BE, Georgiadis A, Hu Y, Perrimon N (2016). Mapping signaling pathway cross-talk in Drosophila cells. Proc Natl Acad Sci U S A, 113(35), 9940-9945. Abstract.  Author URL.
Wang H, Becuwe M, Housden BE, Chitraju C, Porras AJ, Graham MM, Liu XN, Thiam AR, Savage DB, Agarwal AK, et al (2016). Seipin is required for converting nascent to mature lipid droplets. Elife, 5 Abstract.  Author URL.
Chavez A, Scheiman J, Vora S, Pruitt BW, Tuttle M, P R Iyer E, Lin S, Kiani S, Guzman CD, Wiegand DJ, et al (2015). Highly efficient Cas9-mediated transcriptional programming. Nat Methods, 12(4), 326-328. Abstract.  Author URL.
Housden BE, Valvezan AJ, Kelley C, Sopko R, Hu Y, Roesel C, Lin S, Buckner M, Tao R, Yilmazel B, et al (2015). Identification of potential drug targets for tuberous sclerosis complex by synthetic screens combining CRISPR-based knockouts with RNAi. Sci Signal, 8(393). Abstract.  Author URL.
Lin S, Ewen-Campen B, Ni X, Housden BE, Perrimon N (2015). In Vivo Transcriptional Activation Using CRISPR/Cas9 in Drosophila. Genetics, 201(2), 433-442. Abstract.  Author URL.
Housden BE, Lin S, Perrimon N (2014). Cas9-based genome editing in Drosophila. Methods Enzymol, 546, 415-439. Abstract.  Author URL.
Housden BE, Terriente-Felix A, Bray SJ (2014). Context-dependent enhancer selection confers alternate modes of notch regulation on argos. Mol Cell Biol, 34(4), 664-672. Abstract.  Author URL.
Simón R, Aparicio R, Housden BE, Bray S, Busturia A (2014). Drosophila p53 controls Notch expression and balances apoptosis and proliferation. Apoptosis, 19(10), 1430-1443. Abstract.  Author URL.
Li J, Housden BE, Bray SJ (2014). Notch signaling assays in Drosophila cultured cell lines. Methods Mol Biol, 1187, 131-141. Abstract.  Author URL.
Mohr SE, Hu Y, Kim K, Housden BE, Perrimon N (2014). Resources for functional genomics studies in Drosophila melanogaster. Genetics, 197(1), 1-18. Abstract.  Author URL.
Housden BE, Perrimon N (2014). Spatial and temporal organization of signaling pathways. Trends Biochem Sci, 39(10), 457-464. Abstract.  Author URL.
Housden BE, Li J, Bray SJ (2014). Visualizing Notch signaling in vivo in Drosophila tissues. Methods Mol Biol, 1187, 101-113. Abstract.  Author URL.
Babaoğlan AB, Housden BE, Furriols M, Bray SJ (2013). Deadpan contributes to the robustness of the notch response. PLoS One, 8(9). Abstract.  Author URL.
Ren X, Sun J, Housden BE, Hu Y, Roesel C, Lin S, Liu L-P, Yang Z, Mao D, Sun L, et al (2013). Optimized gene editing technology for Drosophila melanogaster using germ line-specific Cas9. Proc Natl Acad Sci U S A, 110(47), 19012-19017. Abstract.  Author URL.
Housden BE, Fu AQ, Krejci A, Bernard F, Fischer B, Tavaré S, Russell S, Bray SJ (2013). Transcriptional dynamics elicited by a short pulse of notch activation involves feed-forward regulation by E(spl)/Hes genes. PLoS Genet, 9(1). Abstract.  Author URL.
Housden BE, Millen K, Bray SJ (2012). Drosophila Reporter Vectors Compatible with ΦC31 Integrase Transgenesis Techniques and Their Use to Generate New Notch Reporter Fly Lines. G3 (Bethesda), 2(1), 79-82. Abstract.  Author URL.
Bernard F, Krejci A, Housden B, Adryan B, Bray SJ (2010). Specificity of Notch pathway activation: twist controls the transcriptional output in adult muscle progenitors. Development, 137(16), 2633-2642. Abstract.  Author URL.
Pines MK, Housden BE, Bernard F, Bray SJ, Röper K (2010). The cytolinker Pigs is a direct target and a negative regulator of Notch signalling. Development, 137(6), 913-922. Abstract.  Author URL.
Krejcí A, Bernard F, Housden BE, Collins S, Bray SJ (2009). Direct response to Notch activation: signaling crosstalk and incoherent logic. Sci Signal, 2(55). Abstract.  Author URL.

Publications by year


2017

Housden BE, Muhar M, Gemberling M, Gersbach CA, Stainier DYR, Seydoux G, Mohr SE, Zuber J, Perrimon N (2017). Loss-of-function genetic tools for animal models: cross-species and cross-platform differences. Nat Rev Genet, 18(1), 24-40. Abstract.
Housden B, Nicholson H, Perrimon N (2017). Synthetic Lethality Screens Using RNAi in Combination with CRISPR-based Knockout in Drosophila Cells. BIO-PROTOCOL, 7(3).

2016

Mohr SE, Hu Y, Ewen-Campen B, Housden BE, Viswanatha R, Perrimon N (2016). CRISPR guide RNA design for research applications. FEBS J, 283(17), 3232-3238. Abstract.  Author URL.
Housden BE, Perrimon N (2016). Cas9-Mediated Genome Engineering in Drosophila melanogaster. Cold Spring Harb Protoc, 2016(9). Abstract.  Author URL.
Housden BE, Perrimon N (2016). Comparing CRISPR and RNAi-based screening technologies. Nat Biotechnol, 34(6), 621-623. Author URL.
Chavez A, Tuttle M, Pruitt BW, Ewen-Campen B, Chari R, Ter-Ovanesyan D, Haque SJ, Cecchi RJ, Kowal EJK, Buchthal J, et al (2016). Comparison of Cas9 activators in multiple species. Nat Methods, 13(7), 563-567. Abstract.  Author URL.
Housden BE, Perrimon N (2016). Design and Generation of Donor Constructs for Genome Engineering in Drosophila. Cold Spring Harb Protoc, 2016(9). Abstract.  Author URL.
Housden BE, Hu Y, Perrimon N (2016). Design and Generation of Drosophila Single Guide RNA Expression Constructs. Cold Spring Harb Protoc, 2016(9). Abstract.  Author URL.
Housden BE, Perrimon N (2016). Detection of Indel Mutations in Drosophila by High-Resolution Melt Analysis (HRMA). Cold Spring Harb Protoc, 2016(9). Abstract.  Author URL.
Zacharioudaki E, Housden BE, Garinis G, Stojnic R, Delidakis C, Bray SJ (2016). Genes implicated in stem cell identity and temporal programme are directly targeted by Notch in neuroblast tumours. Development, 143(2), 219-231. Abstract.  Author URL.
Ammeux N, Housden BE, Georgiadis A, Hu Y, Perrimon N (2016). Mapping signaling pathway cross-talk in Drosophila cells. Proc Natl Acad Sci U S A, 113(35), 9940-9945. Abstract.  Author URL.
Wang H, Becuwe M, Housden BE, Chitraju C, Porras AJ, Graham MM, Liu XN, Thiam AR, Savage DB, Agarwal AK, et al (2016). Seipin is required for converting nascent to mature lipid droplets. Elife, 5 Abstract.  Author URL.

2015

Chavez A, Scheiman J, Vora S, Pruitt BW, Tuttle M, P R Iyer E, Lin S, Kiani S, Guzman CD, Wiegand DJ, et al (2015). Highly efficient Cas9-mediated transcriptional programming. Nat Methods, 12(4), 326-328. Abstract.  Author URL.
Housden BE, Valvezan AJ, Kelley C, Sopko R, Hu Y, Roesel C, Lin S, Buckner M, Tao R, Yilmazel B, et al (2015). Identification of potential drug targets for tuberous sclerosis complex by synthetic screens combining CRISPR-based knockouts with RNAi. Sci Signal, 8(393). Abstract.  Author URL.
Lin S, Ewen-Campen B, Ni X, Housden BE, Perrimon N (2015). In Vivo Transcriptional Activation Using CRISPR/Cas9 in Drosophila. Genetics, 201(2), 433-442. Abstract.  Author URL.

2014

Housden BE, Lin S, Perrimon N (2014). Cas9-based genome editing in Drosophila. Methods Enzymol, 546, 415-439. Abstract.  Author URL.
Housden BE, Terriente-Felix A, Bray SJ (2014). Context-dependent enhancer selection confers alternate modes of notch regulation on argos. Mol Cell Biol, 34(4), 664-672. Abstract.  Author URL.
Simón R, Aparicio R, Housden BE, Bray S, Busturia A (2014). Drosophila p53 controls Notch expression and balances apoptosis and proliferation. Apoptosis, 19(10), 1430-1443. Abstract.  Author URL.
Li J, Housden BE, Bray SJ (2014). Notch signaling assays in Drosophila cultured cell lines. Methods Mol Biol, 1187, 131-141. Abstract.  Author URL.
Mohr SE, Hu Y, Kim K, Housden BE, Perrimon N (2014). Resources for functional genomics studies in Drosophila melanogaster. Genetics, 197(1), 1-18. Abstract.  Author URL.
Housden BE, Perrimon N (2014). Spatial and temporal organization of signaling pathways. Trends Biochem Sci, 39(10), 457-464. Abstract.  Author URL.
Housden BE, Li J, Bray SJ (2014). Visualizing Notch signaling in vivo in Drosophila tissues. Methods Mol Biol, 1187, 101-113. Abstract.  Author URL.

2013

Babaoğlan AB, Housden BE, Furriols M, Bray SJ (2013). Deadpan contributes to the robustness of the notch response. PLoS One, 8(9). Abstract.  Author URL.
Ren X, Sun J, Housden BE, Hu Y, Roesel C, Lin S, Liu L-P, Yang Z, Mao D, Sun L, et al (2013). Optimized gene editing technology for Drosophila melanogaster using germ line-specific Cas9. Proc Natl Acad Sci U S A, 110(47), 19012-19017. Abstract.  Author URL.
Housden BE, Fu AQ, Krejci A, Bernard F, Fischer B, Tavaré S, Russell S, Bray SJ (2013). Transcriptional dynamics elicited by a short pulse of notch activation involves feed-forward regulation by E(spl)/Hes genes. PLoS Genet, 9(1). Abstract.  Author URL.

2012

Housden BE, Millen K, Bray SJ (2012). Drosophila Reporter Vectors Compatible with ΦC31 Integrase Transgenesis Techniques and Their Use to Generate New Notch Reporter Fly Lines. G3 (Bethesda), 2(1), 79-82. Abstract.  Author URL.

2010

Bernard F, Krejci A, Housden B, Adryan B, Bray SJ (2010). Specificity of Notch pathway activation: twist controls the transcriptional output in adult muscle progenitors. Development, 137(16), 2633-2642. Abstract.  Author URL.
Pines MK, Housden BE, Bernard F, Bray SJ, Röper K (2010). The cytolinker Pigs is a direct target and a negative regulator of Notch signalling. Development, 137(6), 913-922. Abstract.  Author URL.

2009

Krejcí A, Bernard F, Housden BE, Collins S, Bray SJ (2009). Direct response to Notch activation: signaling crosstalk and incoherent logic. Sci Signal, 2(55). Abstract.  Author URL.

Back | Edit Profile