Summary

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.

Research Statement

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.

Scientific Publications

Generation and differentiation of induced pluripotent stem cells reveal ankylosing spondylitis risk gene expression in bone progenitors.

Layh-Schmitt G, Lu S, Navid F, Brooks SR, Lazowick E, Davis KM, Montagna C, Gadina M, Colbert RA
Clinical rheumatology.
2017 Jan;
36(1).
doi: 10.1007/s10067-016-3469-5
PMID: 27864696

Loss of bone strength in HLA-B27 transgenic rats is characterized by a high bone turnover and is mainly osteoclast-driven.

Rauner M, Thiele S, Fert I, Araujo LM, Layh-Schmitt G, Colbert RA, Hofbauer C, Bernhardt R, Bürki A, Schwiedrzik J, Zysset PK, Pietschmann P, Taurog JD, Breban M, Hofbauer LC
Bone.
2015 Jun;
75().
doi: 10.1016/j.bone.2015.02.024
PMID: 25746795

HLA-B27 misfolding and ankylosing spondylitis.

Colbert RA, Tran TM, Layh-Schmitt G
Molecular immunology.
2014 Jan;
57(1).
doi: 10.1016/j.molimm.2013.07.013
PMID: 23993278

HLA-B27 alters the response to tumor necrosis factor α and promotes osteoclastogenesis in bone marrow monocytes from HLA-B27-transgenic rats.

Layh-Schmitt G, Yang EY, Kwon G, Colbert RA
Arthritis and rheumatism.
2013 Aug;
65(8).
doi: 10.1002/art.38001
PMID: 23666508

Immature cell populations and an erythropoiesis gene-expression signature in systemic juvenile idiopathic arthritis: implications for pathogenesis.

Hinze CH, Fall N, Thornton S, Mo JQ, Aronow BJ, Layh-Schmitt G, Griffin TA, Thompson SD, Colbert RA, Glass DN, Barnes MG, Grom AA
Arthritis research & therapy.
2010;
12(3).
doi: 10.1186/ar3061
PMID: 20576155

From HLA-B27 to spondyloarthritis: a journey through the ER.

Colbert RA, DeLay ML, Klenk EI, Layh-Schmitt G
Immunological reviews.
2010 Jan;
233(1).
doi: 10.1111/j.0105-2896.2009.00865.x
PMID: 20193000

Education

University of Heidelberg, Germany
Habilitation (Priv. Doz. Dr. rer. nat. habil.)

University of Hohenheim, Germany
Ph.D. (Dr. rer. nat.)

University of Hohenheim, Germany
M.S. , Biology

Experience

Assistant Professor
Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati

Senior Scientist
Health Care Research Center, Procter & Gamble

Privatdozent (Dr. rer. nat. habil.)
University of Heidelberg, Germany

Postdoctoral Fellow
University of Washington, Seattle, WA

Postdoctoral Fellow
Max Planck Institute of Biophysics, Frankfurt, Germany

Last Updated: July 2020