- Past President, International Cytokine & Interferon Society
- Fellow of The American Association for the Advancement of Science (AAAS)
- Fellow of The American Academy of Microbiology (AAM)
- 2005 Seymour & Vivian Milstein Award for Excellence in Interferon and Cytokine Research
Transcription factors modulate diverse gene regulatory networks that govern pluripotency, immune response, differentiation, cell death, proliferation, etc. Most of my studies have centered on the response of cells and organisms to cytokines, interferons, and pathogenic microbes. The studies have converged on the activation of two transcription factor families, the interferon regulatory factors (IRFs), and the signal transducers and activators of transcription (STATs). Our discovery of a transcription factor that is activated in response to dsRNA led to the identification of IRF3. Our studies on the activation of STAT1 revealed mechanisms that regulate its phosphorylation and nuclear trafficking. These findings were recognized with a Seymour & Vivian Milstein Award for excellence in interferon and cytokine research.
Prior to establishing my laboratory, I performed my Ph.D. research in the laboratory of Arnold J. Levine, where I identified p53 stability and expression differences in normal, transformed, and virus-infected cells. Subsequently, I joined the laboratory of James E. Darnell, Jr. as postdoctoral fellow at the Rockefeller University. During that time I identified the DNA regulatory enhancer responsible for the transcriptional response to type I interferons, viral regulation of interferon signaling, and factors that recognize response DNA elements. Since then our laboratory group has made seminal contributions to our understanding of IRF and STAT function by their serine and tyrosine phosphorylation, characterization of mechanisms that regulate their nuclear trafficking, development of a Drosophila transgenic JAK/STAT model, and determination of effects of infection on cytokine and interferon responses.
Recently we have transitioned our investigations to understand the vulnerabilities of KRAS-driven pancreatic cancer. We demonstrated that STAT3 plays a key role in tumor cell differentiation, but it is not required for tumorigenesis in a murine cancer model. We inactivated oncogenic KRAS in pancreatic ductal adenocarcinomas using CRISPR/Cas9 and show that at an advanced tumor stage, dependence on KRAS for tumor growth is reduced and is instead manifested in the suppression of antitumor immunity.