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, in addition to teaching both medical and graduate students. 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 University of Maryland Baltimore. 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. Apart from TLR signaling, we have manipulated the differentiation state of macrophages to become either highly activated ("M1") or alternatively activated ("M2") that contribute to either disease or tissue repair, respectively. Identification of metabolic pathways underlying macrophage differentiation has been a major area of study.  In toto, I have published >300 peer-reviewed publications and >50 invited works. 

The creative use of genetic, molecular, and biochemical approaches, combined with unique animal models of infection or trauma, has led to our history of highly translational work, resulting in the development of multiple novel therapeutic approaches for (1) mitigating disease caused by influenza and respiratory syncytial virus (RSV) infection, (2) development of small molecule TLR antagonists based on the structural interactions of innate signaling molecules, and (3) a prototype nanoparticle-encapsulated vaccine for the biothreat agent, Francisella tularensis.  Recently, we developed a non-replicating adenoviral vector that is engineered to respond to  inflammatory signals, resulting in the the production of the HMGB1 antagonist, Box A. When administered therapeutically during an inflammatory insult, this vector blunts strongly inflammatory responses induced by HMGB1 in vivo such as lethal influenza infection and LPS-induced lethality in mice and cotton rats. Among our most important discoveries was the identification of two novel mutations within the IRAK4 gene in a child who had been seen at the NIH who had exhibited a history of repeated bacterial infections. These same mutations have since been identified in other similar patients. 

We  have also 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 such as RSV infection and inflammatory bowel disease (IBD) and we have published that “TLR4-SNP” mice are hyporesponsive to lipopolysaccharide (LPS) and influenza infection, exhibit increased sensitivity to Gram negative infection and RSV, and are exquisitely sensitive to induction of chemically-induced colitis. Treatment of DSS-treated TLR4-SNP mice with  a PPARgamma agonist ligand that elicits an M2 response, reversed colitic damage.

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 senior administrators. I have directed a T32 Program entitled, “Signaling Pathways in Innate Immunity,” and we are currently in year 13.

macrophages, lipopolysaccharide, Toll-like receptors (TLRs), macrophage differentiation, signaling pathways, interferons, cytokines, influenza, respiratory syncytial virus (RSV), Francisella tularensis, vaccines, dextran sodium sulfate, HMGB1, Box A, Adenovirus vector

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).

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

K. Richard, K.H. Piepenbrink, K. A. Shirey, A. Gopalakrishnan, S. Nallar, D. J. Prantner, D. J. Perkins, W. Lai, A. Vlk, V. Y. Toshchakov, C. Feng, R. Fanaroff, A. E. Medvedev, J. C. G. Blanco, and S. N. Vogel.  Human TLR4 D299G/T399I SNPs: A novel mouse model reveals mechanisms of altered pathogen sensitivity J Exp Med (2021) 218 (2): e20200675 (online ahead of print) doi: 10.1084/jem.20200675.  PMC7685774

A. M. Vlk, D. Prantner, K. A. Shirey, D. J. Perkins, M. S. Buzza, V. Thumbiegere-Math, A. D. Keegan, S. N. Vogel. M2a macrophages facilitate resolution of chemically-induced colitis in TLR4-SNP mice. mBio e01208-23.(2023) doi: 10.1128/mbio.01208-23. PMC10653841

K. A. Shirey, J. Joseph, L. Coughlan, H. Nijhuis, A. W. Varley, J. C. G. Blanco, S. N. Vogel. An adenoviral vector encoding an inflammation-inducible antagonist, HMGB1 Box A: A novel therapeutic approach to inflammatory diseases. mBio Feb 5;16(2):e0338724. (2025) doi: 10.1128/mbio.03387-24. PMC11796352