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University of Exeter Medical School

Dr Benjamin Housden

Dr Benjamin Housden

Associate Professor

 B.Housden@exeter.ac.uk

 01392 72 7475

 Living Systems Institute T04.13

 

Living Systems Institute, University of Exeter, Stocker Road, Exeter, EX4 4QD


Overview

My research is focussed on using interdisciplinary methods to study how genetic mutations lead to disease. This involves a combination of new technology development and high-throughput genetic screening to analyse gene functions and to identify and characterise candidate drugs to treat diseases. The development of new methods to identify effective drugs is vitally important because current methods suffer from a high failure rate that slows the development of new therapies.

Qualifications

  • Ph.D., University of Cambridge, 2010
  • M.A., University of Cambridge, 2005

Career

Dr. Housden began his research career in the laboratory of Professor Sarah Bray at the University of Cambridge. There, he studied the direct transcriptional outputs of Notch signaling and crosstalk with the EGFR pathway using Drosophila as a model system. For his postdoctoral work, he joined Professor Norbert Perrimon’s laboratory at Harvard Medical School. Here, his interest in gene networks led him to develop new genetic screening methods to identify genes that could be targeted to treat human diseases. Since joining the Living Systems Institute in 2017, Dr. Housden’s laboratory has focused on developing new methods to enhance their ability to identify new therapeutic targets for disease and applying these methods for drug discovery.

Employment history:

  • Associate Professor - University of Exeter; 05/2021 to present
  • Research Fellow - University of Exeter; 04/2017 to 05/2021
  • Postdoctoral Fellow - Harvard Medical School; 09/2011 to 03/2017
  • Postdoctoral Fellow - University of Cambridge; 12/2010 to 08/2011

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Research

Research interests

Research in our group is focused on developing new methods and technologies to allow more sensitive and higher throughput genetic screens to be performed. This includes optimisation of screening methods via the application of liquid handling automation, development of new molecular biology techniques to enhance the performance of genetic tools and the application of machine learning to better analyse screen data. Together, these advances will allow us to perform larger and more reliable screens, which can be applied to both fundamental biological investigations and drug-discovery.

In addition, we have several ongoing projects to apply the new screening methods that we develop to identify new drug-targets for human diseases. We are currently working on Tuberous Sclerosis Complex, Neurofibromatosis type 1, Amyotrophic Lateral Sclerosis and several mutations linked to sporadic cancers.

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Publications

Journal articles

Jenkins BH, Maguire F, Leonard G, Eaton JD, West S, Housden BE, Milner DS, Richards TA (2021). Characterization of the RNA-interference pathway as a tool for reverse genetic analysis in the nascent phototrophic endosymbiosis, <i>Paramecium bursaria</i>. ROYAL SOCIETY OPEN SCIENCE, 8(4). Author URL.
Jenkins BH, Maguire F, Leonard G, Eaton JD, West S, Housden BE, Milner DS, Richards TA (2021). Emergent RNA–RNA interactions can promote stability in a facultative phototrophic endosymbiosis. Proceedings of the National Academy of Sciences, 118(38). Abstract.
Nicholson HE, Tariq Z, Housden BE, Jennings RB, Stransky LA, Perrimon N, Signoretti S, Harris IS, Endress JE, Kaelin WG, et al (2019). HIF-independent synthetic lethality between CDK4/6 inhibition and VHL loss across species. Science Signaling, 12(601). Abstract.
Nicholson HE, Housden B, Perrimon N, Kaelin WG (2019). Loss of CDK4/6 Activity is Synthetic Lethal with VHL Inactivation in Clear Cell Renal Cell Carcinoma. The FASEB Journal, 33(S1), 674.9-674.9.
Koca Y, Housden BE, Gault WJ, Bray SJ, Mlodzik M (2019). Notch signaling coordinates ommatidial rotation in the Drosophila eye via transcriptional regulation of the EGF-Receptor ligand Argos. Scientific Reports, 9(1). Abstract.
Xu C, Tang H-W, Hung R-J, Hu Y, Ni X, Housden BE, Perrimon N (2019). The Septate Junction Protein Tsp2A Restricts Intestinal Stem Cell Activity via Endocytic Regulation of aPKC and Hippo Signaling. Cell Reports, 26(3), 670-688.e6.
Lee P-T, Zirin J, Kanca O, Lin W-W, Schulze KL, Li-Kroeger D, Tao R, Devereaux C, Hu Y, Chung V, et al (2018). A gene-specific T2A-GAL4 library for Drosophila. Elife, 7 Abstract.  Author URL.
Sierzputowska K, Baxter CR, Housden BE (2018). Variable Dose Analysis: a Novel High-throughput RNAi Screening Method for Drosophila Cells. Bio-protocol, 8(24).
Mohr SE, Rudd K, Hu Y, Song WR, Gilly Q, Buckner M, Housden BE, Kelley C, Zirin J, Tao R, et al (2018). Zinc Detoxification: a Functional Genomics and Transcriptomics Analysis in Drosophila melanogaster Cultured Cells. G3 (Bethesda), 8(2), 631-641. Abstract.  Author URL.
Rajan A, Housden BE, Wirtz-Peitz F, Holderbaum L, Perrimon N (2017). A Mechanism Coupling Systemic Energy Sensing to Adipokine Secretion. Developmental Cell, 43(1), 83-98.e6.
Housden BE, Li Z, Kelley C, Wang Y, Hu Y, Valvezan AJ, Manning BD, Perrimon N (2017). Improved detection of synthetic lethal interactions in Drosophila cells using Variable Dose Analysis (VDA). Proceedings of the National Academy of Sciences
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).
Valvezan AJ, Turner M, Belaid A, Lam HC, Miller SK, McNamara MC, Baglini C, Housden BE, Perrimon N, Kwiatkowski DJ, et al (2017). mTORC1 Couples Nucleotide Synthesis to Nucleotide Demand Resulting in a Targetable Metabolic Vulnerability. Cancer Cell, 32(5), 624-638.e5.
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.

Chapters

Housden BE, Ewen-Campen B, Mohr SE, Perrimon N (2018). Chapter 9 CRISPR-Based Perturbation of Gene Function in Drosophila Cells. In  (Ed) Drosophila Cells in Culture, Elsevier, 193-206.

Conferences

Nicholson H, Housden B, Perrimon N, Kaelin WG (2019). Abstract C124: HIF-independent synthetic lethality between CDK4/6 inhibition and VHL loss across species.

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