Dr Angus James Cameron

PhD
Senior Lecturer
Group Leader
Research Focus

Protein kinases represent the largest group of drug targets in cancer therapy. My research focuses on kinases regulating cancer cell growth and motility to understand how and when to target them with drugs.

Key Publications

Inhibitor-induced HER2-HER3 heterodimerisation promotes proliferation through a novel dimer interface. Elife (2018) 7. pii: e32271. PMID: 29712619

Knockout of the PKN family of Rho effector kinases reveals a non-redundant role for PKN2 in developmental mesoderm expansion. Cell Reports (2016) 14(3):440-448. PMID: 26774483

mTORC2 targets AGC kinases through Sin1-dependent recruitment. Biochem J (2011) 439(2):287-97. PMID: 21806543

PKC maturation is promoted by nucleotide pocket occupation independently of intrinsic kinase activity. Nat Struct Mol Biol (2009) 16(6):624-30. PMID: 19465915

Major Funding
  • 2018-2021- Worldwide Cancer Research/PCRF Research Grant, Targeting PKN to suppress stromal activation in pancreatic ductal adenocarcinoma, £235,633
Other Activities
  • Member of the Biochem Journal Editorial Panel
  • Advisory Board Member - European Pharma Summit- Design & Screening conference 2017
Research

The targeting of protein kinases represents an opportunity and challenge in cancer treatment. Some 2% of transcribed genes are kinases, many implicated in tumorigenesis and all potentially druggable.

My research encompasses various cancer associated kinases, including PKC, PKN, mTOR and EGFR family tyrosine kinases. In particular, my work on PKC and the HER family of tyrosine kinase growth factor receptors has revealed that inhibitors can have surprising allosteric effects on kinase function with significant implications for therapy.

My group is currently examining the role of the PKN kinases in malignant progression. PKN kinases are effectors of Rho family GTPases, regulating cell shape, adhesion and motility. Our studies on the role for PKN family members in mammalian development has provided significant insight; we have described a key non-redundant role for the PKN2 isoform in the regulation of embryo morphogenesis, cell proliferation and migration; phenotypes critically linked to cancer progression (Cell Reports 2016).

The PKN kinases are dramatically upregulated in many cancers and high expression has been correlated with metastatic disease – the spread of cancer around the body. Our current studies focus on the stromal roles for the PKN kinases in pancreatic and breast cancer, supported by the novel roles we have discovered for PKN during development.

The ultimate goal of this research is to assess whether these kinases represent a significant cancer drug target.

Other Activities
  • Member of the Biochem Journal Editorial Panel
  • Advisory Board Member - European Pharma Summit- Design & Screening conference 2017
  • Athena Swan Committee member - Silver Award 2015/2018
  • Barts Pancreas Tissue Bank (BPTB) committee member: 2017-present
Major Funding
  • 2018-2021- Worldwide Cancer Research/PCRF Research Grant, Targeting PKN to suppress stromal activation in pancreatic ductal adenocarcinoma,'£235,633
  • 2016-2018- Academy of Medical Sciences/Wellcome Trust Springboard Award, Defining the role of PKN2 in cancer-associated fibroblasts, £99,773
Recent Publications

Inhibitor-induced HER2-HER3 heterodimerisation promotes proliferation through a novel dimer interface Claus J, Patel G, Autore F et al. eLife (2018) 7(7)

Towards specific inhibition of mTORC2 Murray ER, Cameron AJM Aging (2017) 9(7) 2461-2462

Genomic Subtypes of Non-invasive Bladder Cancer with Distinct Metabolic Profile and Female Gender Bias in KDM6A Mutation Frequency Hurst CD, Alder O, Platt FM et al. Cancer Cell (2017) 32(7) 701-715.e7

Uncoupling TORC2 from AGC kinases inhibits tumour growth Cameron AJM, Veeriah S, Marshall JJT et al. Oncotarget (2017) 8(7) 84685-84696

PDGFRα depletion attenuates glioblastoma stem cells features by modulation of STAT3, RB1 and multiple oncogenic signals Cenciarelli C, Marei HE, Felsani A et al. Oncotarget (2016) (1)

Knockout of the PKN Family of Rho Effector Kinases Reveals a Non-redundant Role for PKN2 in Developmental Mesoderm Expansion Quétier I, Marshall JJT, Spencer-Dene B et al. Cell Reports (2016) 14(7) 440-448

Targeting protein kinase C in sarcoma Martin-Liberal J, Cameron AJ, Claus J et al. Biochimica et Biophysica Acta - Reviews on Cancer (2014) 1846(7) 547-559

Functional implications of assigned, assumed and assembled PKC structures. Linch M, Riou P, Claus J et al. Biochem Soc Trans (2014) 42(2) 35-41
https://www.ncbi.nlm.nih.gov/pubmed/24450624

Regulation of polarized morphogenesis by protein kinase C iota in oncogenic epithelial spheroids. Linch M, Sanz-Garcia M, Rosse C et al. Carcinogenesis (2014) 35(1) 396-406
http://www.ncbi.nlm.nih.gov/pubmed/24072773

A cancer-associated mutation in atypical protein kinase Cι occurs in a substrate-specific recruitment motif Linch M, Sanz-Garcia M, Soriano E et al. Science Signaling (2013) 6(7)

For additional publications, please click here
Team

Postdoctoral Researchers
Dr Shinelle G. Menezes, Dr Lorena Alba-Catellon

PhD Students
Ms Priththivika Baskaran, Ms Elizabeth Murray, Ms Josie Williams

Biography

I completed my BSc in biochemistry at the University of Bath where I got hooked on research while working on a placement year in the US on protein phosphatases and virology.

I studied for my PhD in Glasgow on a Wellcome Trust Prize studentship working on receptor mediated signal transduction, graduating in 2000. After completing a 2 years Wellcome Trust postdoctoral fellowship in Glasgow, I joined Professor Peter Parker’s lab at the Cancer Research UK London Research Institute where I studied the role PKC family protein kinases in development and cancer.

I joined Barts Cancer Institute in 2013 as an Early Career Researcher in the Centre for Tumour Biology and was promoted to Senior Lecturer in 2018.