Rheumatology

Gerlinde Layh-Schmitt, PhD

Appointment

Assistant Professor

Email

gerlinde.layh-schmitt@cchmc.org

Phone

513-636-3325

Fax

513-636-3328

Credentials

PhD: University of Hohenheim, Germany, 1983
Habilitation (Privatdozent Dr. rer. nat. habil.): University of Heidelberg, Germany, 1995

Awards and Honors

Grant of the Deutsche Forschungsgemeinschaft
Stipend from the Max-Planck Society
Cancerfree kids award

Research

Ankylosing spondylitis (AS) is associated with generalized bone loss, or osteoporosis, and yet there are localized areas of abnormal bone formation. While osteoporosis may be secondary to chronic inflammation, localized bone formation is poorly understood. Overall susceptibility to AS has been linked to a small group of closely related MHC class I molecules, referred to as HLA-B27. One of our goals is to determine how HLA-B27 influences disease pathogenesis, and in particular whether its tendency to misfold and activate the unfolded protein response (UPR), affects myeloid cell development including osteoclast differentiation. The UPR has dramatic effects on Toll-like receptor (TLR) signaling, which in turn alters cytokine responses known to play a role in osteoclast activation. We will use HLA-B27 transgenic animal models and in vitro models, as well as patient-derived samples, to test the hypothesis that UPR-TLR synergy leads to an imbalance of bone remodeling. Additional studies will focus on host pathogen interaction, particularly with organisms suspected as triggers of HLA-B27-associated diseases.

Publications, Most Recent

Will E., Bailey J., Schuesler T., Balcik B., Burzynski B., Witte D., Layh-Schmitt G., von Kalle, C., Baum, C., Sorrentino B., Wagner, L. M, Kelly, P., Reeves, L. and Williams D. A.: Limitations of murine studies in interpreting genotoxicity of retroviral vectors in support of Phase I trials.Mol. Ther. 2007; 782-791.

Layh-Schmitt, G., Rosenstiel. A, Wang, W., Koch, S., Wittlinger, C., Kraft, E., Klanke, C., Bailey, J., Jansen, M., McCaffery, P., v. Kalle, C.. An LMO2 associated Transcription complex activates a truncated form of retinaldehyde dehydrogenase in T cell acute lymphoblastic leukemia (T-ALL). (submitted).

Greis K. D., Zhou S., Siehnel R., Klanke C., Curnow A., Howard J., Layh-Schmitt, G. Development and Validation of an whole cell Inhibition Assay for Bacterial Methionine Aminopeptidase by SELDI-TOF Mass Spectrometry.Antimicrobial Agents and Chemotherapy, 2005; 49: 3428-3434.

Von Kalle, C., Fehse B., Layh-Schmitt, G., Schmidt, M., Kelly, P., Baum, C. Stem cell clonality and genotoxicity in hematopoietic cells: gene activation side effects should be avoidable.Semin Hematol. 2004; 41(4): 303-318.

Presentations, Most Recent

Kraft E., S. Crable, K. Crable, J. Bailey, C. Klanke, C. v. Kalle, G. Layh-Schmitt. LMO2 induced T cell acute lymphoblastic leukemia originates from a differentiation block in T cell development. 5th Annual Midwest Blood Club meeting, Cincinnati OH, USA (2006).

Layh-Schmitt, G., S. Crable, K. Crable, E. Kraft, J. Bailey, C. Klanke, C. v. Kalle. T cell acute lymphoblastic leukemia originates from a differentiation block in T cell development due to aberrant expression of LMO2 and TAL1(SCL). Blood, 106, 628. 48th ASH Annual Meeting, Orlando, FA, USA (2006).

Layh-Schmitt, G., W. Wang, A. Rosenstiel, C. Wittlinger, C. Klanke, J. Bailey, K. Crable, S. Crable, C. v. Kalle. LMO2 induced T cell acute lymphoblastic leukemia originates from a differentiation block in T cell development. 4th Annual Midwest Blood Club meeting, Lexington KY, USA (2006).

Layh-Schmitt, G., W. Wang, A. Rosenstiel. S. Koch, C. Klanke, K. Anderson, P. McCaffery. RALDH2 is regulated by an LMO/SCL(TAL1) associated protein complex in T cell acute lymphoblastic leukemia. 47th ASH Annual Meeting, Atlanta, GA, USA (2005).

Layh-Schmitt, G., W. Wang, A. Rosenstiel, C. Klanke, K. Bohn, C. von Kalle. Molecular mediators of T-cell leukemia in a patient after gene therapy for X-SCID. 3rd Annual Midwest Blood Club meeting, Louisville, KY, USA (2005).

Layh-Schmitt, G., A. Rosenstiel, C. Klanke, K. Bohn, C. von Kalle. Towards the mechanism of LMO2 associated T-cell leukemia. 6th International Symposium and Expert Workshops on Leukemia and Lymphoma, Amsterdam, Netherlands (2005).

Layh-Schmitt, G., A. Rosenstiel, C. Klanke, K. Anderson, C. von Kalle. Aberrant expression of LMO2, TAL1(SCL) and T-RALDH2 in the T-cell clone of a patient with T-ALL like syndrome after gene therapy for X1-SCID. 46th ASH Annual Meeting, San Diego, CA, USA (2004).