The comparative cytological and immunoregulatory phenotypes of canine multicentric and human non-Hodgkin lymphoma
Department: Veterinary Clinical Sciences
This exciting and topical project will be undertaken at both the Camden Campus of the Royal Veterinary College, a vibrant, dynamic and friendly research university, and the Centre for Haemato-Oncology at the Barts Cancer Institute, a world-leading cancer research unit. It is suitable for a veterinary or science graduate interested in clinical aspects of cancer and immune tolerance. The supervisors are all leaders in their respective fields and have extensive experience of PhD supervision. This project will provide an outstanding training experience in basic pathology and a number of fundamental immunological techniques.
The student will be trained in the cytological and histopathological examination of canine and human lymphoma, affording a unique opportunity to work with both veterinary and medical pathologists. The student will also gain a detailed knowledge of the theory and practice of multicolour flow cytometry, in vitro assays of regulatory cell function, and molecular biological aspects of microarray technology and transcriptomics.
The student will become familiar with the relevant bioinformatic techniques to analyse microarray data. In summary, this project will provide a rounded research training experience that will bridge both fundamental science and clinical practice.
Detailed Description of Project
Lymphoma is a common cause of morbidity and mortality in dogs, accounting for 83% of all canine haemopoietic malignancies and up to 24% of all neoplasms in this species. Relatively little is known about the way in which different cytomorphological or immune phenotypes impact the diagnosis and prognosis of this important disease, which is associated with less than 20% survival at two years following a diagnosis. Nevertheless, the most common type of canine lymphoma, diffuse large B cell lymphoma (DLBCL), shows many characteristics in common with the DLBCL subtype of non-Hodgkin lymphoma (NHL) in man, suggesting that it may represent an animal model for NHL. However, a critical comparison of the disease in the two species has not yet been undertaken.
The goal of this project is therefore to advance knowledge of both canine and human lymphoma, comparing the phenotypes of multicentric lymphoma in the dog with NHL in man.
Our aim is to test the hypotheses that the prognosis of canine multicentric lymphoma is related to its cytomorphological and immune phenotype, and that multicentric DLBCL in the dog shows similar phenotypic, immunopathological and clinical characteristics to NHL in man, thus qualifying it as a suitable animal model for the human disease.
Objectives are therefore to determine the cytological, histopathological and immune phenotypes of canine multicentric lymphoma; and to compare the respective mRNA transcriptomes and regulatory phenotypes of canine multicentric DLBCL with those of human NHL, exploring regulatory T cells (Tregs), tumour-associated macrophages and myeloid-derived suppressor cells. A critical comparison of parallel data derived from the dog and man will be made in order to establish the strength of similarity between the diseases in the two species.
For further details please contact Dr Oliver Garden email: firstname.lastname@example.org
Deadline for applications is 12 noon on Monday 3rd December. Interviews to be held Tuesday 15th January.
- Garden, OA, Pinheiro, DY and Cunningham, F (2010) All creatures great and small: regulatory T cells in mice, humans, dogs and other domestic animal species. International Immunopharmacol 11 (5): 576-588
- Gribben, J.G. (2010) Implications of the tumor microenvironment on survival and disease response in follicular lymphoma. Curr Opin Oncol 22(5): 424-430
- Guerard, E.J and Bishop, M.R. (2012) Overview of non-Hodgkin’s lymphoma. Dis Mon 58:208-218
- Marconato, L., Gelain, M.E. and Comazzi, S. (2012) The dog as a possible animal model for human non-Hodgkin lymphoma: a review. Hematol Oncol DOI: 10.1002/hon.2017
- Pinheiro, D, Singh, Y, Grant, C, Appleton, RC, Sacchini, F, Walker, KRL, Chadbourne, AH, Palmer, CA, Armitage-Chan, E, Thompson, I, Williamson, L, Cunningham, F and Garden, OA (2011) Phenotypic and functional characterisation of a CD4+CD25highFOXP3high regulatory T cell population in the dog. Immunol 132(1): 111-122
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