As a staff scientist at the NIAMS, Dr. Gerlinde Layh-Schmitt determined an altered response to TNF-α in HLA-B27 expressing monocytes which promotes osteoclastogenesis in a rat model of Spondyloarthritis. Prior to that, she was a senior scientist at the Health Care Research Center in Mason, OH, where she developed a whole-cell inhibition assay for bacterial methionine aminopeptidase as a novel therapeutic target. At the Privatdozent at University of Heidelberg, Germany, Dr. Layh-Schmitt identified membrane proteins essential for attachment of Mycoplasma pneumoniae to host cells based on the whole genome sequence of the pathogen. Dr. Layh-Schmitt did a postdoctoral fellowship at the Washington University, Seattle, WA, where she identified mechanism by which a pathogenicity factor (porin) is transferred from the pathogen (Neisseria) into host cells.
The major goal of Dr. Layh-Schmitt’s current research is to understand dysregulated bone formation in spondyloarthritis (SpA), including the role of HLA-B27. We have used animal models to evaluate effects of HLA-B27 on osteoclast and osteoblast development and function under inflammatory and non-inflammatory conditions. These studies revealed a novel effect of HLA-B27 misfolding on osteoclastogenesis through ER stress and IL-1α production. Recently, we have developed a robust program using induced pluripotent stem cells (iPSCs) developed from skin fibroblasts to study how SpA risk genes affect osteoblast development and function. Pluripotent stem cells offer many advantages over bone marrow sampling, and can be used to generate other types of disease-relevant cell types such as mesenchymal cells, chondrocytes, adipocytes, and even hematopoietic elements.
Previous research focused on the following: isolation and identification of novel bacteria species involved in herbicide (chloridazon) degradation; identification of bacterial pathogenicity factors and proteins essential for bacteria-host-interactions (Neisseria gonorrhoeae, Mycoplasma pneumoniae); development of anti-infectives against novel therapeutic targets in bacteria; and murine studies explaining the toxicity of retroviral vectors containing the common gamma chain used to cure SCID, but leading to TALL.