Kevin L Bentley PhD

Research Scientist in Epidemiology (Microbial Diseases)

Research Interests

Lymphatics; Lymph nodes; Type 1 diabetes; Sjögren's syndrome; Lymphotoxin; Homeobox genes; Transgenic mice

Research Summary

Dr Bentley’s current research interests lie in 1) the development and regulation of lymphoid organs, 2) the role and regulation of lymphoid neogenesis in disease states, 3) leading to an interest in autoimmune diseases such as Type 1 diabetes and Sjögren’s syndrome, and 4) the development of effective animal models to study these questions. The lymphatic system plays a key role in tissue fluid regulation and tumour metastasis, and the adaptive immune response. Certain aspects of the origins of the lymphatic system in the embryo remain unclear, as do the mechanisms that direct growth of the network of lymphatic vessels in ontogeny following immunization and during chronic inflammation. Specifically, he is interested in whether pathological processes in lymphatic organ and vessel development follow a similar pattern as in embryonic development. What cell types are involved? What cytokines, chemokines, transcription factors and signalling pathways are involved? Dr Bentley is attempting to answer these questions using transgenic reporter mice, in vivo imaging, immunofluorescence, and gene expression techniques. To date, he has used a yeast-based homologous recombination system to design and generate a series of transgenic reporter mice expressing lacZ or green fluorescent protein (GFP) in endothelial cells of lymph node high endothelial vessels, and a red fluorescent protein in endothelial cells of lymphatic vessels. Mice containing these reporters have been mated to produce mice having GFP-tagged blood vessels and RFP-tagged lymphatic vessels in lymph nodes for in vivo imaging of lymphoid development and pathology, and for cell trafficking studies. These mice will also be used with insulin promoter driven lymphotoxin-alpha (LTa) expressing transgenic mice to study T lymphocyte infiltrations in the pancreas.
Dr Bentley has also made transgenic mice expressing human insulin for studying cell trafficking and antigen movement in Type 1 diabetes, and for incorporation in a humanized mouse model under development by the JDRF Diabetes Center at Yale.
Additionally, transgene constructs for salivary gland specific expression of LTa and LTb have been generated and transgenic mice are in the process of being made. These mice will be used to study the role of chronic inflammation in Sjögren’s syndrome and accompanying lymphoma formation.

Extensive Research Description

Dr Bentley’s current research interests lie in 1) the development and regulation of lymphoid organs, 2) the role and regulation of lymphoid neogenesis in disease states, 3) leading to an interest in autoimmune diseases such as Type 1 diabetes and Sjögren’s syndrome, and 4) the development of effective animal models to study these questions. The lymphatic system plays a key role in tissue fluid regulation and tumour metastasis, and the adaptive immune response. Certain aspects of the origins of the lymphatic system in the embryo remain unclear, as do the mechanisms that direct growth of the network of lymphatic vessels in ontogeny following immunization and during chronic inflammation. Specifically, he is interested in whether pathological processes in lymphatic organ and vessel development follow a similar pattern as in embryonic development. What cell types are involved? What cytokines, chemokines, transcription factors and signalling pathways are involved? Dr Bentley is attempting to answer these questions using transgenic reporter mice, in vivo imaging, immunofluorescence, and gene expression techniques. To date, he has used a yeast-based homologous recombination system to design and generate a series of transgenic reporter mice expressing lacZ or green fluorescent protein (GFP) in endothelial cells of lymph node high endothelial vessels, and a red fluorescent protein in endothelial cells of lymphatic vessels. Mice containing these reporters have been mated to produce mice having GFP-tagged blood vessels and RFP-tagged lymphatic vessels in lymph nodes for in vivo imaging of lymphoid development and pathology, and for cell trafficking studies. These mice will also be used with insulin promoter driven lymphotoxin-alpha (LTa) expressing transgenic mice to study T lymphocyte infiltrations in the pancreas.
Dr Bentley has also made transgenic mice expressing human insulin for studying cell trafficking and antigen movement in Type 1 diabetes, and for incorporation in a humanized mouse model under development by the JDRF Diabetes Center at Yale.
Additionally, transgene constructs for salivary gland specific expression of LTa and LTb have been generated and transgenic mice are in the process of being made. These mice will be used to study the role of chronic inflammation in Sjögren’s syndrome and accompanying lymphoma formation.

Selected Publications