Stefanie N. Vogel, PhD

University of Maryland, College Park, Dept. of Microbiology, College Park, MD; B.S., 1972

University of Maryland, College Park, Dept. of Microbiology, College Park, MD; Ph.D., 1977 (Immunology)

National Institute of Dental Research, National Institutes of Health, Bethesda, MD; Post-doctoral fellow (1977-1980)

After more than 40 years in my own laboratory, my record shows that I have developed the scientific expertise and leadership skills required to direct multiple concurrent projects, multi-component projects, and a training program. I am most proud of my first grant that was continuously funded by the NIH for 33 years, during which time it was designated an NIH “Merit Award,” and my recent award of being named ”Distinguished University Professor” by the UMSOM. My focus throughout this time has not changed fundamentally: the analysis of the basic underlying mechanisms by which macrophage differentiation facilitates or restricts infectious agents or tumor growth. My laboratory has made seminal contributions to the area of immunology that we now call “innate immunity,” and specifically, the mechanisms by which Toll-like receptor (TLR) signaling is regulated.

The creative use of genetic, molecular, and biochemical approaches, combined with unique animal models of infection, has led to our most recent, highly translational work, resulting in novel therapeutic approaches for influenza and respiratory syncytial virus (RSV), development of small molecule TLR antagonists based on the structural interactions of innate signaling molecules, and a prototype vaccine for the biothreat agent,Francisella tularensis.

We  have developed a murine model of TLR4 hyporesponsiveness that expresses homologs of two co-segregating single nucleotide polymorphisms (SNPs) in human TLR4 that reduce TLR4 signaling. These SNPs are expressed in patients with many infectious inflammatory diseases and inflammatory bowel disease (IBD) and we have recently published that “TLR4-SNP” mice are hyporesponsive to lipopolysaccharide (LPS), exhibit increased sensitivity to Gram negative infection and RSV, and are exquisitely sensitive to induction of chemically-induced colitis.  The creative use of genetic, molecular, and biochemical approaches, combined with unique animal models of infection and trauma, has led to our most recent, highly translational work, resulting in novel therapeutic approaches for influenza and respiratory syncytial virus (RSV), development of small molecule TLR antagonists, and prototype vaccines for RSV and the biothreat agent, Francisella tularensis, and the therapeutic use of a PPARgamma agonist ligand to treat dextran sodium sulfate (DSS)-induced colitis in the TLR4-SNP mice. In toto, I have published >300 peer-reviewed publications and >50 invited works. Our work is highly translational and has led to the identification of multiple therapeutic approaches for mitigating acute lung injury induced by virus infection.

Mentoring the next generation of scientists is among the most important contributions I have made to science. In addition to teaching microbiology and Immunology to graduate students and medical students, I have mentored more than 39 post-doctoral fellows and 14 graduate students, the majority of whom have remained in science. I am particularly proud of my trainees, with many now in leadership positions at universities, industry, and the NIH or FDA, or immunology societies as bench scientists or administrators. I have directed a T32 Program entitled, “Signaling Pathways in Innate Immunity,” for the past 10 years and we are currently in year 11.

macrophages, lipopolysaccharide, Toll-like receptors (TLRs), macrophage differentiation, signaling pathways, interferons, cytokines, influenza, respiratory syncytial virus (RSV), Francisella tularensis, vaccines, dextran sodium sulfate

A. E. Medvedev, A. Lentschat, D. B. Kuhns, J. C. G. Blanco, C. Salkowski, S. Zhang, M. Arditi, J. I. Gallin, and S. N. Vogel.  Distinct mutations in IRAK-4 confer hyporesponsiveness to lipopolysaccharide and Interleukin-1 in a patient with recurrent bacterial infections.  J. Exp. Med.  198: 521-531 (2003).

A. A. Awomoyi, P. Rallabhandi, T. I. Pollin, E. Lorenz, M. B. Sztein, M. S. Boukhvalova, V. G. Hemming, J. C. G. Blanco, and S. N. Vogel.  Association of TLR4 polymorphisms with symptomatic Respiratory Syncytial Virus infection in high-risk infants and young children.  J. Immunol. 179: 3171-3177 (2007).

K. A. Shirey, W. Lai, A. J. Scott, M. Lipsky, P. Mistry, L. M. Pletneva, C. L. Karp, J. McAlees, T. L. Gioannini, J. Weiss, W. H. Chen, R, K. Ernst, D. P. Rossignol, F. Gusovsky, J. C. Blanco, and S. N. Vogel.  The TLR4 antagonist, Eritoran, protects mice from lethal influenza infection. Nature 497:498-502 (2013) PMC3725830

J. Blanco, M . S. Boukhvalova, L. M. Pletneva, K. Shirey, and S. N. Vogel. A recombinant anchorless Respiratory Syncytial Virus (RSV) fusion (F) protein/monophosphoryl lipid A (MPL) vaccine protects against RSV-induced replication and lung pathology. Vaccine 32:1495-500 (2014).   PMC3947896.

D. J. Perkins, R. Rajaiah, S. M. Tennant, G. Ramachandran, T. H. Dyson, and S. N. Vogel. Salmonella typhimurium co-opts the host type I interferon system to selectively restrict macrophage innate immune transcriptional responses. J. Immunol 195: 2461-2471 (2015). PMC4546913