Dr John Knight

Lecturer in Cancer Biology

View graph of relations

Overview

Protein Synthesis and Cancer Lab (PSC)

Research in the group aims to understand how protein synthesis is altered by tumours to promote their activities. Through collaboration with clinical scientists and fundamental biologists we aim to build our knowledge of cancer and its treatment to improve patient outcomes. We make use of cell and organoid based models as well as tumour tissue from patients. Current projects in the lab include:

1: How do colorectal cancers respond to current chemotherapies? Half of metastatic colorectal cancer patients do not respond to first line treatment, with no biomarkers of resistance currently available to determine which patients will respond. Those patients who do not respond are left with few approved clinical options, particularly the ~50% of patients who have KRAS or BRAF mutations that drive resistance to second line therapy. Through understanding how current therapies alter cancer cell-intrinsic pathways we are uncovering biomarkers of resistance to enable patient stratification and identifying mechanisms to suppress tumour cells that do not respond to treatment.

2: What determines the divergent roles of the translation regulator eEF2K between different tumour types? eEF2K is a negative regulator of protein synthesis, acting by inhibiting the elongation factor eEF2 through reversible phosphorylation. In some tumour types (colorectal, breast and prostate) eEF2K expression is reduced, consistent with rapid translation driving protein synthesis and tumour proliferation. However, in other tumours (ovarian and AML) eEF2K expression is elevated, with the slowing of translation essential for preserving energy levels within tumour cells. The reasons behind the choice individual tumour types make is unclear but presents a druggable target through modulation of eEF2K activity. We are seeking to understand the pleiotropy of eEF2K by analysing its activity across tumour types. In parallel we are aiming to uncover potential drug targets altering eEF2K and translation elongation for future exploitation.

Biography

I completed my PhD at the University of York with Prof Jo Milner, investigating post-translational regulation of p53, cancer metabolism and ribosome biogenesis. I then moved to the group of Prof Anne Willis at the MRC Toxicology Unit in Leicester. There I worked on projects investigating the dysfunction of the protein synthesis in sub-physiological conditions and disease. I developed methods for the assessment of the rates of translation elongation and proposed a model for how changes in elongation speed can alter the global proteome. Having collaborated with the Sansom group during my time in Leicester, I then moved to Glasgow to work with Owen on a project looking at the role of KRAS in generating drug resistance in colorectal cancer. Since 2022, I am a Lecturer in the Division of Cancer Sciences leading a research programme identifying methods to improve colorectal cancer treatment and patient stratification. I am a discovery scientist and take a highly collaborative approach to my work, working with clinical and industrial partners. 

Education / academic qualifications

  • Doctor of Philosophy, Regulation of SIRT1 protein in cancer metabolism and ribosome biogenesis (2008 - 2012)
  • Bachelor of Science University of York (2005 - 2008)

Related information

Publication highlights

Research output: Contribution to journalArticlepeer-review

Research output: Contribution to journalArticlepeer-review

Research output: Contribution to journalReview articlepeer-review

Research output: Contribution to journalArticlepeer-review

Research output: Contribution to journalArticlepeer-review

Research output: Contribution to journalArticlepeer-review

View all publications (29)