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Wendy F Davidson
 

Wendy F Davidson Ph.D.

Academic Title: Adjunct Associate Professor
Primary Appointment: Microbiology and Immunology
wedavidson@som.umaryland.edu
Location: BIOPARK 1 - 311
Phone: (410) 706-8188
Fax: (410) 706-8234

Research Interests:

The major focus of my laboratory is to better understand the link between systemic autoimmunity and B cell lymphomagenesis. It is well documented that patients with SLE, rheumatoid arthritis and autoimmune thyroiditis have a significantly increased risk of developing B cell lymphomas. In addition, patients with mutations in FAS or FASL and associated Autoimmune Lymphoproliferative Disease (ALPS), have an increased susceptibility to a wide variety of cancers including B cell lymphomas. Consistent with these findings, we reported that C3H and BALB/c mice with mutations in Fas (lpr) or Fasl (gld), develop B cell malignancies with high frequency by ~ 1 year of age. These tumors, secreted Ig, were mostly Ig isotype switched, and were classified as plasmacytoid lymphomas (PL). Recently, we showed that our large panel of gld PL are almost exclusively derived from autoreactive B cells specific for Ig or nuclear antigens, suggesting that chronically stimulated autoreactive B cells may be particularly susceptible to transformation. Gene expression profiling, revealed that both primary and transplanted PL share a transcriptional profile that places them at an early stage in plasma cell differentiation and distinguishes them from other B cell neoplasms identified in the mouse. A number of genes were identified that were selectively up or down regulated in PL and may be relevant to pathogenesis. Two genes whose expression was increased, Il-10 and BAFF may provide a link between autoimmunity and B cell transformation. Our future goals are to further investigate the importance of the discriminating genes in the transformation process and to compare the PL transcriptome with that of pre-malignant B cells at the polyclonal and oligoclonal stages of disease progression. The importance of IL-10 in autoimmunity and tumorigenesis is being investigated further using mice deficient in Fasl and Il-10.

In other studies, we identified novel Fas-dependent and Fas-independent, caspase-independent cell death pathways in activated T cells that induce non-apoptotic death. Current studies are focused on identifying the death receptor/ligand pairs that trigger Fas-independent death and the molecular components of the death pathways. In addition, we are investigating the possibility that non-apoptotic death in gld T cells is pro-inflammatory and is a factor in autosensitization.

Publications:

Zhang, J.Q., C. Okumura, T. McCarty, M. S. Shin, P. Mukhopadhyay, M. Hori, T.A. Torrey, Z. Naghashfar, J.X. Zhou, D.Roopenian, H. C. Morse III, and W. F. Davidson. 2004. Evidence for Selective Transformation of Autoreactive Immature Plasma Cells in Mice Deficient in Fasl.

Borges, V.M., M.F. Lopes, H., Falcao, J.H. Leite-Junior, P.M. Rocco, W.F. Davidson, R. Linden, W.A. Zin and G.A. DosReis. 2002. Apoptosis underlies immunopathogenic mechanisms in acute silicosis. Am. J. of Respir. Cell Mol. Biol. 27:78-84.

Davidson, W.F., C. Haudenschild, J. Kwon and M. Williams. 2002 T cell receptor ligation triggers novel nonapoptotic cell death pathways that are Fas-independent or Fas-dependent. J. Immunol. 169:6218-30.

Ostler, T., W.F. Davidson, and S. Ehl. 2002. Virus clearance and immunopathology by CD8+ T cells during infection with respiratory syncytial virus are mediate by IFN-gamma. Eur. J. Immunol. 32:2117-2123.

Borges, V.M., H. Falcao, J.H. Leite-Junior, L. Alium, G.P. Teixeia, M. Russo, A.F. Nobrega, M.F. Lopes, P.M. Rocco, W.F. Davidson, R. Linden, H. Yagita, W.A. Zin and G.A. DosReis. 2001. Fas ligand triggers pulmonary silicosis. J. Exp. Med. 194:155-164.

Scott, D.W., D. Donjerkovic,. W. F. Davidson, G. Carey, C. Mueller, S. Liu,, and L. Tonnetti, 2000. B-cell receptor and Fas-mediated signals for life and death. Immunol. Reviews 176: 105-115.

Sharma, K., R.X. Wang. L.Y. Zhang, D.L. Yin, X.Y. Luo, J. Soloman, D.W. Scott, W. F. Davidson, and Y.F. Shi. 2000. Death the Fas way: Regulation and Pathophysiology. Pharmacol. Therapeut. 88:333-347.