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Trine Jorgensen, Ph.D.
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Area of general research interest:
- Autoimmunity
- Systemic lupus erythematosus
- Gender differences
- The role of interferons in autoimmunity
Current program:
- Molecular mechanisms of gender differences in mouse lupus-like disease
- A new mouse model of Sjogrens Syndrome
Investigators:
- Angela Johnson , PhD, Post doc Fellow
- Natalia Giltiay, PhD, post doc Fellow
- Nodoka Sakurai, MD, Volunteer
Collaborators:
- Xiaoxia Li, PhD, Department of Immunology, Cleveland Clinic
- Loren D. Erickson, PhD, University of Virginia, Charlottesville, VA
- Divaker Choubey, PhD, University of Cincinnati, OH
- Shozo Izui, MD, C.M.U., Geneva, Switzerland
Brief Description:
The incidence of many autoimmune diseases is higher in women than in men. This bias is thought to be a result of genetic susceptibility and environmental factors, including exposure to sex hormones. This concept is supported by the fact that many women are between the ages of 15 and 40 when diagnosed with autoimmune diseases.
Our laboratory (established at the Institute in 2007) focuses on the effects of sex hormones on the immune system during initiation/progression of lupus-like disease in mice. Spontaneous mouse models of autoimmunity includes the New Zealand hybrid ((NZB x NZW)F1) mouse model of systemic lupus erythematosus (SLE). This proven model of SLE develops several manifestations similar to those seen in human patients. Of particular interest is the fact that predominantly female (NZB x NZW)F1 mice develop the disease. Thus, this model is extremely useful for studies investigating the interrelationship of sex hormones and autoimmunity.
Our studies aim to identify the molecular and cellular signatures associated with early lupus-like disease characteristics, such as hypergammaglobulinemia and anti-nuclear autoantibody production. Our goal is to identify new biomarkers/biosignatures for early detection of disease. In addition, we are specifically investigating whether sex hormones are involved in the control of type I interferon production/signaling, as we and others have previously described how manipulating levels of type I interferons in female lupus-prone mice can alter disease incidence and kinetics.
Key References:
Gubbels MR, et al. MHC and gender on lupus-like autoimmunity in Nba2 congenic mice. J Immunol 2005;175:6190-6.
Trine N. Jørgensen, Joshua Thurman, Shozo Izui, Michael T. Falta, Troy E. Metzger, Shannon A. Flannery, John Kappler, Philippa Marrack, Brian L. Kotzin. 2006. Genetic Susceptibility to PolyI:C-Induced IFNa/b-dependent Accelerated Disease in Lupus-Prone Mice. Genes and Immunity 7:555-567.
Trine N. Jørgensen, Ellen Roper, Joshua M. Thurman, Philippa Marrack, Brian L. Kotzin. 2007. Type I interferon signaling is involved in the spontaneous development of lupus-like disease in B6.Nba2 and (B6.Nba2 x NZW)F 1 mice. Genes and Immunity 8:653-662.
Jørgensen TN, et al. Bim and Bcl-2 mutually affect the expression of the other in T cells. J Immunol 2007;179:3417-24.
Melanie R. Gubbels Bupp , Trine N. Jørgensen, Brian L. Kotzin. 2008. Identification of candidate genes that influence sex hormone dependent disease phenotypes in mouse lupus. Genes and Immunity 9:47-56.