The research being conducted in my laboratory aims to identify the pathogenetic mechanisms involved in systemic autoimmune diseases using a mouse model that develops a spontaneous lupus nephritis that is very similar to human SLE. Our studies have shown that improper regulation of the production of IdLNF1-expressing antibodies is involved, and we recently identified a peptide structural motif that all of the IdLNF1 antibodies express, that induces activation of autoreactive T cells. Vaccination with this peptide delays disease onset, and currently, we are trying to understand what cells and mechanism(s) are involved. Since the mouse model we use shows an increased incidence of disease in females like humans, we are also exploring how gonadal steroid hormones modulate disease. We have found that the administration of estrogen to male SNF1 mice, which do not develop lupus, results in accelerated nephritis and decreased survival, with the onset of clinical disease and immune cell phenotypes involved exactly mirroring spontaneous disease in females. We are using this model to understand whether estrogen receptor expression on immune cells is responsible, in part, for gender bias in immune responses, including autoimmune disease. Exposure to some toxic chemicals that behave like estrogen, such as dioxin, has been suggested to induce and/or modulate autoimmune diseases including SLE and diabetes, and we have demonstrated that exposure to relatively low levels of dioxin accelerates disease in male SNF1 mice. Metal exposure is also suspect, and we will also use this model and its nonautoimmune haplotype-matched control, DBA/1 X Balb/c, to study gestational and adult immunotoxicologic effects of lead and mercury exposure.
As part of my mission to Animal Science, I develop immune methodology for use in cows and sheep. Research projects that I will be involved in will include studies of M. paratuberculosis infection in cattle and sheep, and characterization of immunosuppression in dairy cattle, with a focus to derive strategies to improve animal health, and production. One new focus is the development of a low-cost, simple, and sensitive penside diagnostic assay for Johne’s Disease. Similar approaches can be used for the development of assays against other pathogens. I will also carry out studies as determined by the Immunology Core of the Johne’s Disease Integrated Program, recently funded by the USDA. I am also looking at the immunomodulatory effects of L-canavanine, leptin and conjugated linoleic acid.
Selected Recent Publications:
Stoll ML. Price KD. Silvin CJ. Jiang F. Gavalchin J. Immunization with peptides derived from the idiotypic region of lupus-associated autoantibodies delays the development of lupus nephritis in the (SWR x NZB)F1 murine model. Journal of Autoimmunity. 29(1):30-7, 2007 Aug.
Pilones, K. Lai, Z. Gavalchin, J. Prenatal HgCl2 Exposure Alters Fetal Cell Phenotypes. Journal of Immunotoxicology. 4(4):295-301, October 2007.
Nedrow AJ. Gavalchin J. Smith MC. Stehman SM. Maul JK. McDonough SP. Thonney ML. Antibody and skin-test responses of sheep vaccinated against Johne's Disease. Veterinary Immunology & Immunopathology. 116(1-2):109-12, 2007 Mar 15.
Gavalchin, J., et al, Immunity and You –web and CD Immunology Curriculum for high school