Dr James Wells
Dr James Wells

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"As a child I was always interested in how things worked and was constantly asking people questions they couldn’t possibly know the answers to," says Dr James Wells, Research Fellow in the Epithelial Cancer Group at The University of Queensland Diamantina Institute (UQDI). Wells' curiosity hasn't abated, but his questions are now focused on the role the immune system plays in recognising and controlling skin cancer.

 

Wells enrolled as a Zoology undergraduate at the University of Edinburgh, but soon switched to Immunology, and a project during his honours year roused a strong interest in dendritic cells (DCs). Part of the early immune response to infection, DCs intercept intruders such as viruses or bacteria, then teach other immune cells to recognise and attack them.  

Dr Wells received his PhD from King’s College London in 2004, working with Dr Joanna Galea-Lauri and Professor Farzin Farzaneh where he studied DCs in the context of cancer, an opportunity he felt was too good to miss. Cancer is notoriously good at evading the immune system, so Wells researched the use of DCs to activate the immune system against cancer. While this approach showed promise, Wells wanted to learn more about immunotherapy in order to find out how to optimise the anti-cancer effect. 
 
At the end of his PhD Wells was advised to seek research experience in asthma and allergy in order to broaden his knowledge of immunology. "It meant learning a whole new area," says Wells, "but it was good advice." He then under took two postdoctoral positions: firstly with Dr Alistair Noble at the MRC & Asthma UK Centre in Allergic Mechanisms of Asthma in London, UK, where he studied vaccine-induced modulation of allergic airway inflammation. He studied another immune cell type, T-cells, to see if they could be modified to alter the immune response in established inflammatory conditions.
 
Wells returned his focus to cancer immunology when an opportunity arose to work with Professor Chris Evans at Harvard Medical School in the US. There, Wells and his colleagues searched for protein fragments, called peptides, derived from tumour genes. Their aim was to use the peptides to generate an immune response against specific cancers.
 
"We discovered that through slightly modifying tumour peptides we could activate the immune response so that it would still recognise the original peptides and hence destroy tumour cells.”
 
The resulting vaccine technology has the potential to refocus an existing immune response or could be used to generate a new immune response capable of attacking infected or malignant cells. Wells established a research program aimed at optimising this immunotherapy approach for Ewing's Sarcoma and was subsequently promoted to a faculty position at Harvard Medical School as an Instructor in 2008.
 
In 2011, Wells joined UQDI for the opportunity to work with Professor Ian Frazer, whose expertise in cancer immunotherapy and vaccine development was of great interest to Wells. He joined UQDI as a Perpetual Trustees Fellow and is now a Senior Research Fellow and Group Leader, focusing on the immunopathology of Squamous cell carcinoma (SCC) in the skin and the development of a therapeutic vaccine.
 
He explains that while it is now possible to activate cancer-specific immune responses, we now know that other regulatory immune responses intervene, preventing cancer clearance.
 
"We want to activate one aspect of the immune response, while stripping away the regulatory immune effect that protects cancer," he says.
 
As part of this endeavour, Wells is working with Professor Peter Soyer, Director of the Princess Alexandra Hospital Dermatology Department. This collaboration enables access to patient samples, and in turn, research developments will be translated back to the clinic.
 
If successful, this work could lead to the development of a therapeutic vaccine for skin cancer.
 
"It will also represent a major advance in our understanding so that we can fight all cancers," says Wells. This is an exciting prospect, he adds, "I find it very easy to get out of bed in the morning and feel I’m doing something of value with my life.”

 

 

Telephone: +61 7 3443 6983

 

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10 Recent Publications
 
Moyle, Peter M., Dai, Wei, Liu, Tzu-Yu, Hussein, Waleed M., Maruthayanar, Pirashanthini, Wells, James W., McMillan, Nigel A. J., Skwarczynski, Mariusz and Toth, Istvan (2015) Combined synthetic and recombinant techniques for the development of lipoprotein-based, self-adjuvanting vaccines targeting human papillomavirus type-16 associated tumors. Bioorganic and Medicinal Chemistry Letters, 25 23: 5570-5575. doi:10.1016/j.bmcl.2015.10.049
 
Liu, F., Ferreira, E., Porter, R. M., Glatt, V., Schinhan, M., Shen, Z., Randolph, M. A., Kirker-Head, C. A., Wehling, C., Vrahas, M. S., Evans, C. H. and Wells, J. W. (2015) Rapid and reliable healing of critical size bone defects with genetically modified sheep muscle. European Cells and Materials, 30 30: 118-131.
 
Roufaiel, Marian Nassef Kadry Naguib, Wells, James W. and Steptoe, Raymond J. (2015) Impaired T-cell function in B-cell lymphoma: a direct consequence of events at the immunological synapse?. Frontiers in Immunology, 6 258.1-258.10.

Collin, Joseph F., Wells, James W., Czepulkowski, Barbara, Lyne, Linden, Duriez, Patrick J., Banham, Alison H., Mufti, Ghulam J. and Guinn, Barbara-ann (2015) A novel zinc finger gene, ZNF465, is inappropriately expressed in acute myeloid leukaemia cells. Genes Chromosomes Cancer, 54 5: 288-302. 

Jung, Ji-Won, Overgaard, Nana H., Burke, Michael T., Isbel, Nicole, Frazer, Ian H., Simpson, Fiona and Wells, James W. (2015) Does the nature of residual immune function explain the differential risk of non-melanoma skin cancer development in immunosuppressed organ transplant recipients?. International Journal of Cancer, 

Bergot, Anne-Sophie, Monnet, Nastasia, Tran, Son Le, Mittal, Deepak, Al-Kouba, Jane, Steptoe, Raymond J., Grimbaldeston, Michele A., Frazer, Ian H. and Wells, James W. (2015) HPV16 E7 expression in skin induces TSLP secretion, type 2 ILC infiltration and atopic dermatitis-like lesions. Immunology and Cell Biology, 93 6: 540-547. 

Overgaard, Nana H., Jung, Ji-Won, Steptoe, Raymond J. and Wells, James W. (2015) CD4+/CD8+ double positive T cells: more than just a developmental stage?. Journal of Leukocyte Biology, 97 1: 31-38. 

Burke, Michael T., Isbel, Nicole, Barraclough, Katherine A., Jung, Ji-Won, Wells, James W. and Staatz, Christine E. (2015) Genetics and nonmelanoma skin cancer in kidney transplant recipients. Pharmacogenomics, 16 2: 161-172. 

Freeman, Andrew, Bridge, Jennifer A., Maruthayanar, Pirashanthini, Overgaard, Nana H., Jung, Ji-Won, Simpson, Fiona, Prow, Tarl W., Soyer, H. Peter, Frazer, Ian H., Freeman, Michael and Wells, James W. (2014) Comparative Immune Phenotypic Analysis of Cutaneous Squamous Cell Carcinoma and Intraepidermal Carcinoma in Immune-Competent Individuals: Proportional Representation of CD8+ T-Cells but Not FoxP3+ Regulatory T-Cells Is Associated with Disease Stage. PLoS One, 9 10: e110928.1-e110928.9. 

Bergot, Anne-Sophie, Ford, Neill, Leggatt, Graham R., Wells, James W., Frazer, Ian H. and Grimbaldeston, Michele A. (2014) HPV16-E7 expression in squamous epithelium creates a local immune suppressive environment via CCL2- and CCL5- mediated recruitment of mast cells. PLoS Pathogens, 10 10: 1-11. 

 

The laboratory is interested in understanding the immunopathology of Squamous Cell Carcinoma and novel factors that regulate CD8 T-cell function in the skin. We are also interested in understanding how immunosuppressive drugs lead to tumour formation and affect naïve and memory T-cell function in other contexts, such as skin immunity and bone healing. There are 8 major research themes in the laboratory.

  • Novel pathways of CD8 T-cell regulation in the skin
  • The role of CD4/CD8 double-positive T-cells in skin immunity
  • The contribution of T-cell suppression to Squamous Cell Carcinoma development
  • The impact of T-cell suppression on bone healing
  • The testing of novel therapeutic compounds on Squamous Cell Carcinoma growth and survival
  • The impact of immunosuppression on T-cell residency in human skin
  • The role of chemokines in the advancement of Squamous Cell Carcinoma
  • Novel strategies to improve antibody-based therapies for cancer

2011-2016: Perpetual Trustees Fellowship. James Wells. $1000K.

2014-2015: Cancer Council Queensland. JW Wells, IH Frazer. AP1069748. Chemokine involvement in the differential response of actinic Keratosis and Squamous Cell Carcinoma to Imiquimod therapy. $200K.

2015-2017: ARC Discovery Project Grant. JW Wells, RJ Steptoe, IH Frazer. DP150103714. Deciphering novel control mechanisms in the skin. $464K.