The focus of our initial studies has been on patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT) as curative therapy primarily for hematological malignancies. More than 50% of HSCT recipients develop chronic Graft-Versus-Host-Disease (cGVHD), a multi-organ autoimmune-like disorder, and the oral cavity (oral mucosa or salivary glands) is affected in a majority of cGVHD patients. While mucosal manifestations are readily evaluable, pathologic changes in salivary glands progress silently from periductal and diffuse lymphocytic infiltrates to destruction of secretory acini and irreversible glandular fibrosis, with severe consequences on oral health, nutrition and quality of life. Understanding the mechanisms underlying salivary gland destruction may contribute to development of targeted therapies and non-invasive methods for serial screening and treatment of post-transplant patients prior to glandular destruction. We are investigating immune and physiologic causes of salivary gland dysfunction following allogeneic hematopoietic stem cell transplant, the pathogenesis of oral cGVHD, with associated clinical trials work directed toward advancing cGVHD therapy. Our recent work has identified immune cell populations in cGVHD-affected oral mucosa and salivary glands including CD4, CD8+T cells, regulatory and IL17-producing T cells. Analysis of the local biofluid of the oral cavity, saliva, shows close association between Th1 cytokines and chemokines and clinical disease severity. Using immunohistochemistry, we have detected production of the interferon-induced GTPase protein MxA (myxoma resistance protein A) in human salivary glands and oral mucosa, providing direct evidence for active type 1 interferon signaling in cGVHD-affected oral tissues. These studies are ongoing, and are contributing to a clear characterization of the pathogenic process of oral cGVHD in the salivary glands and oral mucosa that will lead to identification of additional therapeutic targets. Ongoing clinical trial work includes characterization and sampling of the oral cavity in patients following HSCT in conjunction with the NIH interdisciplinary cGVHD group and prospective therapeutic clinical trial evaluating the efficacy of 0.05% clobetasol oral rinse for treatment of moderate-severe oral cGVHD.

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Dental & Craniofacial Research
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Hickman, Heather D; Mays, Jacqueline W; Gibbs, James et al. (2018) Correction: Influenza A Virus Negative Strand RNA Is Translated for CD8+ T Cell Immunosurveillance. J Immunol 201:2187
Hickman, Heather D; Mays, Jacqueline W; Gibbs, James et al. (2018) Influenza A Virus Negative Strand RNA Is Translated for CD8+ T Cell Immunosurveillance. J Immunol 201:1222-1228
Kerep, Ana Zelic; Broome, Jacob; Pirsl, Filip et al. (2018) Impact of the 2014 NIH chronic graft-versus-host disease scoring criteria modifications assessed in a large cohort of severely affected patients. Bone Marrow Transplant :
Goklemez, Sencer; Pirsl, Filip; Curtis, Lauren M et al. (2017) Clinical significance of IgE in a large cohort of patients with moderate or severe chronic graft-versus-host disease. Am J Hematol 92:E162-E164
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Pirsl, Filip; Curtis, Lauren M; Steinberg, Seth M et al. (2016) Characterization and Risk Factor Analysis of Osteoporosis in a Large Cohort of Patients with Chronic Graft-versus-Host Disease. Biol Blood Marrow Transplant 22:1517-1524
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Kuzmina, Zoya; Gounden, Verena; Curtis, Lauren et al. (2015) Clinical significance of autoantibodies in a large cohort of patients with chronic graft-versus-host disease defined by NIH criteria. Am J Hematol 90:114-9
Curtis, Lauren M; Datiles 3rd, Manuel B; Steinberg, Seth M et al. (2015) Predictive models for ocular chronic graft-versus-host disease diagnosis and disease activity in transplant clinical practice. Haematologica 100:1228-36

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