Research

The Herzog lab’s mission is to perform high quality translational studies aimed at elucidating common mechanism(s) of multiple forms of pulmonary fibrosis. These studies employ a unique combination of murine modeling and novel bioengineering-based approaches, as well as studies in primary human cells, that are aimed at unveiling the immunopathogenesis of human lung fibrosis.

The central focus of our laboratory is the role of Semaphorin 7a in these diseases. Semaphorin 7a (Sema 7a) is a neuronal guidance protein and immunoregulatory molecule about which little is known. In addition to its role in axon guidance, Sema 7a participates in the activation of both macrophages and lymphocytes though its precise contribution to disease remains unclear. We have found that Sema 7a promotes a profibrotic monocyte phenotype characterized by the upregulation of scavenger receptors and secretion of selected soluble mediators, as well by inducing collagen expression in these circulating cells. In fact, our work in a murine model of lung specific, doxycycline inducible TGFb1 overexpression demonstrates that hematopoetic expression of Sema 7a is sufficient to induce fibrosis in the murine lung, and that these effects are mediated at least in part via CD4+ T cells. These latter findings are quite remarkable as while CD4 cells are known to be dispensible for the development of bleomycin-induced lung fibrosis, accumulating evidence suggests that T cells might promote or suppress fibrosis in certain circumstances. Our data indicate that Sema 7a is a central mediator of these responses in the murine lung and, potentially in such diverse human diseases as IPF, Scleroderma related interstitial lung disease (SSc-ILD), and pulmonary sarcoidosis. Current studies in this area are aimed at clarifying the role of Sema 7a’s receptors (CD29 and Plexin C1) as well as other Sema 7a related molecules and signaling pathways in these processes. Another important area of Dr. Herzog’s work involves the application of bioengineering based strategies to the study of lung fibrosis. As part of the first team to develop a bioartificial lung based on decellularized rat lung scaffolds suitable for in vivo implantation, Dr. Herzog has spent the last few years modifying these scaffolds for use in murine and human modeling systems and now has in place a dedicated scaffold based system that can support the growth of cell lines or primary. This approach is ideal in its ability to enable the studies of cell:matrix interactions.

Last, perhaps most reflecting Dr. Herzog’s training as a physician scientist, the lab is also leading the search for predictive peripheral blood biomarkers of disease activity in IPF, SSc-ILD, and sarcoidosis. As a member of the NIH funded MAPGEN and GRADS consortiums, the Herzog lab collaborates with physician scientists across the country to recruit, characterize, and immunophenotype peripheral blood samples from patients with a wide variety of fibrosing diseases.

1. Semaphorin 7a and its downstream signaling pathways in the immunopathology of pulmonary fibrosis.
2. Application of bioengineering strategies to lung biology.
3. Development of peripheral blood biomarkers of disease activity in IPF, SSc-ILD and sarcoidosis.