BUSM’s Mizgerd Awarded Five-Year NIH Grant
Joseph P. Mizgerd, ScD, a Professor of Medicine, Microbiology, and Biochemistry and Director, Pulmonary Center at BUSM, was recently awarded a five-year grant valued at $410,194 per year from the National Institutes of Health for his project titled Cytokine-stimulated systemic defenses during pneumococcal pneumonia. Dr. Mizgerd and colleagues will be testing the hypotheses that macrophages recognizing pneumococcus in the lungs send signals to the liver to activate blood-borne innate immune responses that fight off the bacteria, and that pneumococci which subvert these signaling pathways are especially virulent and capable of causing bacteremic pneumonia. Participating investigators on the grant include Assistant Professors Lee Quinton and Matt Jones from the Pulmonary Center and Professor Stephen Pelton, Director of BMC Pediatric Infectious Diseases.
The major focus of work in Dr. Mizgerd’s laboratory is on acute lower respiratory tract infections. Inflammatory responses in the lungs require the coordinated expression of diverse mediators including adhesion molecules, chemokines, colony stimulating factors, and cytokines that are absent or present only at low levels in uninfected lungs, but are expressed at high levels during infection. Similar mediators are induced during most lung infections, although individual mediators can have different roles during different infections. Dr. Mizgerd studies the coordinated expression of these mediators focusing on gene regulation. NF-kB transcription factors are critical to the gene expression program directing inflammation in the lungs, with RelA inducing inflammatory genes mediating host defense and p50 counteracting this gene induction to prevent lung injury. These transcription factors have cell-specific roles during infection. In addition expression of these mediators is regulated post-transcriptionally by miRNAs that target cytokine mRNAs to limit their expression, and modifications of these miRNAs to relieve miRNA-mediated repression to facilitate cytokine expression. An improved knowledge of the molecular mechanisms directing inflammation in the lungs will provide new directions for preventing acute lower respiratory tract infections.