Comparative Cancer Genetics
These researchers are using next-generation technologies to characterize evolutionarily conserved and species-specific alterations that contribute to the origin, progression, and biological behavior of cancer through comparative approaches with naturally occurring tumors of dogs, mice, and humans. They have already generated and published well-integrated data showing conserved, "horizontal" genomic changes in mouse, human, and dog cancers, as well as "vertically"-integrated features within species. Their datasets already include tumor:normal exome sequencing from dogs, RNA sequencing (mRNA and microRNA) from dogs, mice (including xenografts), and humans, and they are working on creating new datasets for genome-wide methylomes from dogs and humans, ChIP-seq from canine tumors, and libraries from massive parallel sequencing of rearranged lymphocyte antigen receptors to quantify clonal expansion in tumors and in the periphery during anti-tumor immune responses. Their data constitute a canine microcosm that is comparable in scope (albeit not in size) to TCGA, and which they are comparing with relevant entries in TCGA. This work spans tumor genomics and tumor immunology in models of non-Hodgkin lymphoma, osteosarcoma, soft tissue sarcomas, melanomas, renal cell carcinomas, and models for immune response to these tumors.
The researchers are also expanding their efforts to explore autoimmunity as "the other side of the coin" to tumor immunology, where one represents aberrant, excessive autoreactivity (too much immunity) and the other represents aberrant, insufficient autoreactivity (cancer). For this, they are exploring the transcriptomes of antigen-specific autoreactive lymphocytes in diabetes, and the changes in these transcriptomes as we induce therapeutic tolerance.
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