Distinguished Professor of Pharmacology, Ben and Wands Hildyard Chair for Mitochondrial and Metabolic Diseases, American Cancer Society Research ProfessorUniversity of California, San Diego
I have spent my entire academic career investigating stress and inflammation signaling covering the entire gamut of research approaches from basic biochemistry through molecular cell biology to animal pathophysiology. After discovering how environmental stress caused by either infection, inflammation or exposure to toxic substances leads to activation of AP-1, NF-κB and other transcription factors, we begun to examine the role of the key signaling pathways controlling these transcription factors in the pathogenesis of cancer, degenerative and metabolic diseases. My group has identified some of the fundamental mechanisms through which inflammation and obesity promote tumor development and progression and contribute to type II diabetes and insulin resistance. We were also among the first to highlight the role of inflammation in metabolic disease. We had established the mechanisms through which members of the IL-6 cytokine family contribute to the development of colorectal and liver cancer through activation of STAT3 and other transcription factors. We had established the complex and cell type specific mechanisms through which NF-κB activation via IkB kinases (IKK) controls development and progression of colon, liver and prostate cancers. We were amongst the first to demonstrate that not only innate immune cells, especially macrophages, but also adaptive immune cells, including T regulatory cells and B lymphocytes, contribute to tumorigenesis and its progression. Through this work, I have contributed to the founding of the Inflammation and Cancer field. More recently, my laboratory demonstrated the existence of immunosuppressive plasma cells and their role in negative regulation of immunogenic chemotherapy. Much of this work focused on hepatocellular carcinoma (HCC) and my lab was the first to establish a robust and accurate mouse model for studying non-alcoholic steatohepatitis (NASH)-induced HCC. We used this model to establish the adaptive immune mechanism that controls HCC development.