Professor Ade Whitehouse

Profile

I obtained a BSc in Microbiology from the University of Sheffield in 1991 and D.Phil in Molecular Virology from the University of Oxford in 1994. Following postdoctoral work at the Molecular Medicine Unit, St James’s Hospital in Leeds, I was awarded a Medical Research Council Non-clinical Fellowship in 1998, and joined the School of Molecular & Cellular Biology, University of Leeds, as a Lecturer in 2002, and subsequently appointed to Reader in 2005, and Professor of Molecular Virology in 2010.

Research interests

Viruses and Cancer

Infection is a major cause of cancer worldwide. Viruses are associated with approximately 10-15% of human cancers, resulting in about 2 million new cases every year in the world. Research in the the Whitehouse laboratory aims to understand how viruses cause cancer and develop novel antiviral strategies to prevent infection and tumourigenesis. We study the molecular biology of the two most recently discovered human tumour viruses.

(i) Kaposi's sarcoma associated herpesvirus (KSHV) is associated with a variety of lymphoproliferative disorders including Kaposi's sarcoma (KS). Widespread HIV infection has now turned KS into an epidemic disease in Africa. KS is now the most common adult tumour in sub-Saharan Africa. Like other herpesviruses, KSHV has two distinct forms of infection, latency and lytic replication, whic are required for KSHV-mediated pathogensis. Therefore, we have a major research focus to study the molecular mechanisms which regulate lytic gene expression to provide a better understanding of KSHV pathogenesis.

(ii) Merkel cell polyomavirus (MCPyV) is associated with the majority of Merkel cell carcinomas (MCC) is a highly aggressive skin cancer. Due to its recent discovery, little is known about the link between MCPyV and MCC. Therefore, we are currently investigating the role of MCPyV encoded proteins in transformation and immortalisation of human cells.

Current Projects

 1. Identification of essential virus-host cell interactions which are required for virus replication or transformation.

We utilise a range of cutting-edge transcriptomic and quantitative proteomic approaches to globally identify how viral proteins affect the cellular environment. These interactions can then be verified using biochemical and con-focal imaging techniques. This is helping to identify essential virus-host cell interactions which we can target by novel antiviral strategies to inhibit virus replication and transformation.

We are particularly interested in virus-host cell interactions which:
1. Control virus and cellular RNA processing during infection, specifically at the epitranscriptomic level
3. Regulate viral and cellular translation control, specifically by the production of specialised ribosomes
3. Initiate the aggressive metastatic potential of some virus-induced cancers

2. Structural-based rational drug design approaches to inhibit oncogenic viruses.

To date, there are limited antiviral strategies for oncogenic viruses. Although vaccines have been developed for a few of these viruses, these are not available for all the 7 oncogenic viruses, incluing KSHV and MCPyV. Therefore novel antiviral straetgies are required to combat these important human pathogens.

Upon identification of essential virus-host cell interactions using transcriptomic and quantitative proteomic approaches, we utilise a structural-based rational drug design approach to molecular model and design small molecules to inhibit these interactions. Virtual high-throughput screening campaigns are conducted from a large libraries of commercially available compounds. Docking routines and ligand-similarity searches are utilised to design compounds which have the potential to inhibit these essential virus-host cel interactions. Once the virtual high-throughput screening campaign has been performed selected compounds are then assessed in virus-based assays for antiviral activity.

• Action in solution: Embedding new technology and new capability in Biomolecular Interactions in the University of Leeds
• Host-virus interactions in KSHV-related malignancies: evaluating the role of STIP/HOP as a therapeutic target
• Live cell imaging capability for research on pathogenic viruses
• Mass spectrometry infrastructure for in-cell structural biology
• RiboCode - Unlocking the secrets of specialised ribosomes across eukaryotes
• Royal proteins: role in KSHV RNA processing to novel antiviral approaches
• Targeting transfer RNA-derived fragments during KSHV infection
• Virus manipulation of host non-coding RNA regulatory networks

Qualifications

• BSc, Sheffield
• DPhil, Oxford

Professional memberships

• Microbiology Society
• American Society of Microbiology

Student education

I teach molecular virology, cell biology and cancer biology at undergraduate and taught postgraduate levels. 

Undergraduate project topics:

• Investigation of viral-host cell interactions in oncogenic viruses
• Gene Therapy approaches

Postgraduate studentship areas:

• Virus-host cell interactions involved in KSHV lytic replication
• Roles of MCPyV oncogenic proteins in MCC

Research groups and institutes

• Cancer
• Cell and Organismal Biology
• Structural Biology