Howard Young joined the National Cancer Institute in 1983 as an independent investigator and is now a Senior Investigator in the Cancer and Inflammation Program, Center for Cancer Research at the National Cancer Institute at Frederick, in Frederick, MD. He is a Past President of the International Society for Interferon and Cytokine Research, has served on the ICIS Council for the last 3 years and for over 15 years has been on the ICIS Membership Committee. He founded and currently edits the ICIS newsletter. He is a member of the American Academy of Microbiology, the Faculty of 1000 and he has also served as Chair of the Immunology Division of the American Society for Microbiology. He was co-founder and Chair of the NIH Cytokine Interest Group (2 times) and is now an elected member of the NIH Immunology Interest Group steering committee and the NIH Assembly of Scientists. He is a two-time Recipient – National Cancer Institute – of the NIH Director’s Award for Mentoring and a Recipient – National Public Service Award from the American Society for Public Administration and the National Academy of Public Administration.
He has established an NIH Interferon Club and an NIH Microbiome Working Group, both designed to bring together investigators involved in interferon research or microbiome research in order to promote interactions and collaborations across the NIH. He has been working on varying aspects of innate immunity for over 30 years, and has a long history of studying cytokine gene expression and signaling, the biology and molecular biology of NK cells, the generation and analysis of murine macrophage cell lines and immune signaling networks; all of which has resulted in over 300 publications. His initial studies involved molecular characterization of the transcriptional regulation of Interferon-γ and was the first investigator to demonstrate epigenetic control of IFN-γ expression as mediated by methylation of a core regulatory element in the IFN-γ promoter. Following these studies, his laboratory began to focus on the effects of IFN-γ on the host. Given that the IFN-γ gene has been cloned from many different species, sequence comparisons have revealed that the AU rich element in the 3’UTR of the gene is more conserved than the coding region. Based on this evolutionary conservation, he asked a very basic research question, i.e. what are the consequences to the host if the conserved ARE region is removed. He found that low levels of circulating IFN-γ are observed in this mouse, consistent with levels that are observed in patients who have chronic inflammation. Analysis of the mouse has revealed differences in the phenotype dependent on the mouse genetic background. On the Balb/c background he reported that the mice develop aplastic anemia as well as accumulation of calcium in the liver and kidneys, resulting in death by 8 weeks of age. In contrast, on the BL/6 genetic background, the mice develop a lupus like condition as well as primary biliary cholangitis (PBC). Furthermore, the PBC has a female bias and is the first mouse model to mimic the human disease with respect to gender differences. These findings thus represent a novel mouse model of disease that will be important in developing new therapeutic approaches, as current treatments are inadequate and non-specific.
