Faculty of Biological Sciences

Prof Adrian Whitehouse

BSc, Sheffield; DPhil, Oxford
Professor of Molecular Virology
School of Molecular and Cellular Biology

Background: Postdoctoral Research Fellow 1994-1998, Molecular Medicine Unit, Leeds; MRC Non-Clinical Research Fellow, 1998-2001, Molecular Medicine Unit, Leeds. Appointed Lecturer 2002, Reader 2005 and to Professor in 2010.

Contact:  Garstang 9.59, +44(0) 113 34 37096, email address for  

You can read more about Prof Whitehouse's interests here:
www.fbs.leeds.ac.uk/staff/Whitehouse_A/

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 focus on studying the molecular biology of the two most recently discovered human tumour viruses, Kaposi's sarcoma-associated herpesvirus and Merkel cell polyomavirus.

(i) Kaposi's sarcoma associated herpesvirus (KSHV)
This is a human gamma-2 herpesviruses which has been associated with a variety of lymphoproliferative disorders including Kaposi's sarcoma (KS), primary effusion lymphoma and multicentric Castleman's disease. Widespread HIV infection has now turned KS into an epidemic disease in Africa. KS is now the most common adult tumour in parts of Africa. Like other herpesviruses, KSHV has two distinct forms of infection, latency and lytic replication. Although latency has been implicated in tumourigenesis, reactivation and lytic replication play an important part in the pathogenesis and spread of KSHV infection. Therefore, we have a major research focus to study the molecular mechanisms which regulate reactivation and lytic gene expression to provide a better understanding of KSHV pathogenesis.

(ii) Merkel cell polyomavirus (MCPyV)
Merkel cell carcinoma (MCC) is a highly aggressive human cancer of the skin that occurs in elderly and immunosuppressed patients. Merkel cell polyomavirus was discovered in 2008 and is present in 80% of human Merkel cell carcinomas. Therefore, MCPyV is likely to have a causative role in MCC. 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 are utilising 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. Regulate reactivation in Kaposi's sarcoma associated herpesvirus
2. Regulate virus RNA processing
3. Immune evasion strategies employed by oncogenic viruses
4. Virus-host cell interactions required for 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.

 

Faculty Research and Innovation



Studentship information

Undergraduate project topics:

  • Investigation of viral-host cell interactions in oncogenic viruses
  • Development of herpesvirus-based gene delivery vectors
  • Keywords: Cancer, oncogenic viruses, herpesvirus, polyomavirus, gene therapy, viral vectors, molecular biology

Postgraduate studentship areas:

  • Virus-host cell interactions involved in viral mRNA export
  • Identification of oncoproteins encoded by McPyV
  • Development of Herpesvirus-based Gene Delivery Vectors

See also:

Modules taught

BIOC1301 - Introductory Integrated Biochemistry: the Molecules and Processes of Life
BIOC3111/12/BIOL3112/MICR3120 b - ATU - Gene Therapy
BIOC3231/32/3900/BIOL3211/MICR3212 - ATU - Molecular Oncology
BIOC3231/32/BIOL3211/MICR3212 A - ATU - Life of an RNA
BIOC3231/32/BIOL3211/MICR3212 D - ATU - Human-microbe interactions
BIOC3900/BIOL3211/BMSC3233/34/36 - ATU - Cancer Therapy/Biology
BIOL2301/03/05/MICR2320 - Skills for Biol Sci, Biosciences and Microbiology
BIOL3398 - Research Tools and Applications
BIOL3399 - Extended Research Project Preparation
BIOL5296M - Treatment of Infectious Disease and Cancer
BIOW5901X - Foundation module
BIOW5907X - Biocatalysis
BMSC2210 - Chemotherapy
BMSC2233 - Topics in Medical Sciences
MICR2120/BIOC2301 - Integrated Biochemistry/Medical Bacteriology
MICR2121 - Molecular Virology
MICR3211/BIOL3210 A - ATU - emerging infections
MICR3325 - Skills for Microbiologists 3

Centre membership: The Astbury Centre for Structural Molecular Biology

Group Leader Prof Adrian Whitehouse  (Professor of Molecular Virology)

Dr Belinda Baquero  (Research Fellow)

Dr Sophie Schumann  (Research Fellow)


Postgraduates

Alexander Coleman (Primary supervisor) 100% FTE
Samuel Dobson (Primary supervisor) 90% FTE
Zoe Lear (Primary supervisor) 34% FTE
Nnenna Nwogu (Primary supervisor) 70% FTE
Gabriele Stakaityte (Primary supervisor) 75% FTE
Aikaterini Douka (Co-supervisor) 20% FTE
Shola Richards (Co-supervisor) 50% FTE