Cell Signalling (Cancer Biology)

The Cell Signalling Research Group in the Department of Cancer Biology and Pathology has worked to identify novel signalling pathways regulated by different members of the RAS family.

Looking upwards at the glass structure of the Paul O'Gorman Building

Dr Pablo Rodriguez-Viciana

UCL Cancer Institute

Introduction

We use biochemistry, molecular and cellular biology as well as transgenic models to study how RAS family GTPase signal and carry out their multiple cellular functions. Using genomic and proteomic approaches we have identified several novel signalling pathways regulated by different members of the RAS family. Our overall goal is to characterize these novel RAS family effector pathways and to analyse their roles in tumorigenesis, with the ultimate aim of identifying and validating novel targets of therapeutic intervention for the treatment of human cancer.

Research Interests

RAS genes (H-, N- and K-RAS) are mutated in ~30% of human tumours and likely play a role by indirect activation (e.g. by receptor tyrosine kinases) in an even larger number of cancers. RAS mutations are also found in developmental disorders such as Costello and Noonan syndrome.

RAS proteins function as molecular switches, with ON and OFF states. They are activated in response to extracellular signals and when in their ON state, interact with a wide array of downstream targets or effectors to regulate multiple biological processes, including proliferation, differentiation, survival and motility. Analysis of mutations in human tumours has validated both RAF and PI3-kinase as crucial RAS effectors in human tumorigenesis and both are the subject of intense research by pharmaceutical companies. However, data from a variety of experimental systems strongly suggests that additional effectors play critical contributions to RAS-induced tumour formation.

RAS proteins belong to a family of closely related GTPases called the RAS family. Several members of this family share biochemical and biological properties with the RAS proteins, including the ability to act as oncogenes. Their roles in tumorigenesis and how signalling specificity is achieved among closely related members is still poorly understood.

Group members

  • Kristina Klupsch PhD (Research Fellow)
  • Marta Munoz-Alegre MPhil (Research Assistant)
  • Nicole Hartig MSc (PhD student)
  • Berna Demiray MSc (PhD student)
  • Anne Roehrig MSc (PhD student)
  • Lucy Young BSc (Research Technician)