Professor of Medicine University of Massachusetts Medical School
Dr. Fitzgerald received her B.Sc. in Biochemistry in 1995 from University College Cork, Ireland, and her Ph.D. in 1999 from the laboratory of Professor Luke Oâ€™Neill in Trinity College Dublin, Ireland. From 1999 to 2002, she was a post-doctoral fellow in the Department of Biochemistry at Trinity College Dublin. Dr. Fitzgerald joined the Division of Infectious Disease at the University of Massachusetts Medical School as a recipient of a Wellcome Trust International Award in 2001. In 2004 she joined the Faculty as an Assistant Professor. She is currently Professor of Medicine and Director of the Program in Innate Immunity.
Research in the Fitzgerald laboratory is focused on all things related to innate immunity and the inflammatory process, with signal transduction and gene regulation being her particular area of expertise. Active research areas include: (1) biology and role of inflammasomes in anti-microbial immunity (2) cytosolic nucleic acid recognition systems in anti-viral defense and autoimmune disease, (3) long non-coding RNAs in the immune system and (4) innate immunity to Malaria. Enabling these studies, her research spans the disciplines of immunology, cell and molecular biology, biochemistry and genetics.
Dr. Fitzgerald entered the field of immunology by discovering Mal/TIRAP, a central adapter in TLR4 signaling. Since then, she has discovered TRAM, an adapter molecule important downstream of TLR4 in controlling interferon production. Since starting her own lab at UMASS, she has made multiple discoveries that have continued to impact our understanding of host-pathogen interactions. These include the discovery of TBK1/IKKe responsible for the activation of IRF3 and IRF7. Dr. Fitzgerald has also made major contributions to our understanding of the inflammasome where she identified the AIM2 inflammasome important in host-defense to viruses and bacteria. Recent studies have advanced our understanding of how Gram negative bacteria are detected by the NLRP3 inflammasome. Her lab identified a TRIF dependent pathway that licenses NLRP3 inflammasome activation through engagement of the caspase-11 protease. Finally, newer work in her lab has begun to examine the impact of long non-coding RNA species which are induced during host-pathogen interactions and which in turn act to coordinate transcriptional responses in innate immunity.
Professor of Medicine University of Maryland School of Medicine
Dr. Stefanie Vogel received her Ph.D. from the University of Maryland, College Park in 1977 and then did postdoctoral research at the National Institute of Dental Research; Laboratory of Microbiology and Immunology, NIH under Dr. Joost Oppenheim where she characterized inheritance and mapped the Lps gene in macrophages and showed that interferons, and particularly endogenous IFN-b production by macrophages, contributed significantly to macrophage responses to bacterial products such as LPS. Â In 1980, she began a 22 year academic career at the Uniformed Services University of the Health Sciences, Bethesda, MD where she rose to the rank of Professor. Â In 2002, she joined the University of Maryland School of Medicine as Professor of Microbiology and Immunology and Professor of Medicine. Throughout her career, she has had continuous NIH grant support for her research (including an NIH Merit Award) and has received numerous invitations to speak on her current studies at many national and international meetings, including the NIH Immunology Interest Group, the American Association of Immunologists, the former ISICR, the International Endotoxin and Innate Immunity Society, the Society for Leukocyte Biology, and Toll Meetings. Her CV lists over 290 peer-reviewed publications, many in high impact journals, 37 book chapters and reviews and 5 patents. To date, she has mentored 35 post-doctoral fellows and 11 graduate students, and is currently director of a NIH Training Grant, Signaling Pathways in Innate Immunity.
Dr. Vogel’s research is focused on the capacity of macrophages to respond to bacterial products such as the endotoxic lipopolysaccharide (LPS) of Gram negative bacteria. Their studies on the role of Toll-like receptors (TLRs) in this process has led to the dissection of intracellular signaling pathways that define TLR responses to different pathogens, suggesting that these receptors have evolved to enable the host to respond appropriately to specific pathogens. In addition to examining the expression of a variety of proinflammatory genes and interferons as a consequence of exposure of macrophages to LPS and other microbial products, the Vogel laboratory is also actively studying mechanisms by which the inflammatory response to infection is controlled in mice and in humans. Specifically, they have utilized a paradigm of in vitro and in vivo â€œendotoxin toleranceâ€Ë‡ in which macrophages or mice exposed to a relatively low dose of LPS become transiently refractory to subsequent challenge to a variety of TLR agonists. An analysis of the kinase and DNA binding activities of signaling components involved in the TLR4 and TLR2 signaling pathways have been examined systematically by her group, in addition to studies that demonstrate dysregulated interactions among intracellular proteins required for this activation. This is best exemplified by work carried out by her group that identified the underlying genetic defect in a child with severe, recurrent bacterial infections as an IRAK4 deficiency. Lastly, the Vogel laboratory has also pursued mechanisms of inflammatory damage in many animal models where cytokines and IFNs figure centrally in disease progression, pathology, and resolution (e.g., stroke, encephalitic viruses, cecal ligation and puncture-induced polymicrobial sepsis, hemorrhagic shock, Respiratory Syncytial Virus (RSV) infection, and more recently, influenza infectoin). The work in the Vogel laboratory is highly translational: using TLR4 antagonists to block influenza-induced acute lung injury, the re-purposing of FDA-approved drugs that increase expression of M2 macrophages to resolve RSV-induced pathology, and development of a TLR2 antagonist using Computer Aided Drug Design to target a region within the TLR2 TIR domain, are all examples of her most recent efforts to apply our basic understanding of the role of cytokines and interferons to the resolution of diseases.
Young Investigators to Watch for 2018
Here are some of the emerging scientists in the field of interferon and cytokine research:
Dr. Rajsbaum performed his PhD in the laboratory of Anne O’Garra at the MRC-NIMR, London in 2009, and completed his postdoctoral training at Mount Sinai School of Medicine, New York, with Dr Adolfo Garcia-Sastre.