Microgenomics 2021 webinar : Analysis of immune and inflammatory signaling in colonic microadenomas

Описание: Dr. Daniel W. Rosenberg obtained his Doctoral Degree in Environmental Health Sciences at the University of Michigan. He began his research career in molecular pharmacology at The Rockefeller University in the Laboratory of Attallah Kappas, where he attained the rank of Assistant Professor. After moving to the University of Connecticut in 1991, he was appointed as the HealthNet, Inc. Chair in Cancer Biology and Professor of Medicine in the School of Medicine. He has developed an active research program that focuses on the pathogenesis of gastrointestinal diseases and has also established a translational research program in Colon Cancer Prevention, serving as its Director. The long‐term goals of the Program are to improve the early detection of cancer, develop population‐based studies of cancer risk and develop effective chemoprevention strategies for the treatment of high‐risk individuals. Dr. Rosenberg has published a number of recent papers that define the epigenetics of early human neoplasia in the colon, as well as the mutational, transcriptional and microbiome profiles that are associated with neoplastic progression. Research in the Rosenberg Lab extends across a wide range of research topics in colon cancer biology, applying sophisticated mouse genetic cancer models to further our understanding of carcinogenic mechanisms and to identify novel chemoprevention strategies. He is particularly interested in how nutrition influences cancer risk via changes to the microbiome, thereby affecting colonic homeostasis both in healthy and diseased tissues. As part of his nutritional-cancer approach, his lab has a particular interest in how prostaglandins and one-carbon metabolism may be therapeutically targeted for providing durable cancer prevention.


Stromal cells play an important role in promoting colorectal cancer progression. In this study, we have analyzed molecular changes associated with the epithelial and stromal compartments of lesions associated with early colonic neoplasia found in normal screening colonoscopy subjects. Our focus is on microadenomas (less than 5-mm) that are formed in the proximal colon, a region where rapidly developing ‘interval’ cancers often occur. In order to study these small lesions, we have combined laser-capture microdissection with high-sensitivity targeted gene expression profiling.

We report strong activation of a panel of neutrophil/monocyte chemokines, a finding that is consistent with ongoing localized inflammation. Our data also indicate reduced interferon signaling and cell-based immunity. The immune checkpoint and T cell exhaustion gene, PDCD1, was one of the most significantly up-regulated genes, a finding accompanied by decreased cytotoxic T cell effector gene expression. Additionally, CDKN2A expression was strongly up-regulated in the stroma and down-regulated in the epithelium, consistent with a set of alterations often found in senescence-associated signaling pathways. These findings have several important implications, including reduced CD8 T cell infiltration and increased T cell PD1 expression occurring within microadenomas found in the ascending colon. These changes occur within the context of a robust inflammatory response and potential stromal cell senescence, thus providing new insight into potential promotional drivers that may underlie rapid cancer development in the ascending colon.