Location: Cleveland Clinic Main Campus
Current Program Identification of cellular targets of type I interferon in mouse lupus-like disease The etiology of type I interferon-independent neuropsychiatric lupus The role of TLR7 in driving lupus-like disease using conditional KO animals
I received my training first at Novo Nordisk a/s, the world’s leading producer of Insulin for type I diabetics. It was in this environment that my interest for autoimmunity was awakened. I joined the laboratory of Dr. Brian Kotzin in 2001, as his ground-breaking work on systemic lupus erythematosus (SLE) using a combination of genetic, molecular and immunological approaches was intriguing and interesting. SLE is a devastating systemic autoimmune disorder with symptoms varying from non-life-threatening to severe, often leading to premature death. There is no cure for SLE and treatment options remain few and non-specific. The training I received in Dr. Kotzin’s lab was outstanding and has served as a base for both my educational and research related activities since. In 2004, I took the position of Instructor, while working with Drs. Philippa Marrack and John Kappler, before moving to the Cleveland Clinic as an independent investigator.
Today, my research is focused on delineating therapeutic targets affecting autoimmune disease initiation and progression, and to use this information towards the development of new therapeutic agents. I actively collaborate with several local and national colleagues to elucidate the etiology of SLE focusing on sex disparities in lupus, TLR7-dependent regulation of type I interferons and downstream effects, and neuropsychiatric features of SLE. My lab works closely with Drs. Howard Smith and Emily Littlejohn at the Adult Lupus Clinic at the Cleveland Clinic Department of Rheumatology on patient sample-based studies, as well as with other investigators at the Lerner Research Institute.
I am committed to the education of graduate students, medical students and fellows at the Cleveland Clinic and surrounding universities. As such, I have and currently mentor PhD students from a number of local/regional institutions, medical students from the CCLCM program, and undergraduate students. I am the Associate director of Research within the CCLCM medical school located at the Cleveland Clinic, the Director for Problem-based Learning at CCLCM, and an active member of the Research Education Committee and Medical School Promotion Review Committee. I have received several awards for my commitment and engagement in graduate-level education, supporting my commitment to the education of the next generation of scientists.
Our laboratory (established at the Institute in 2007) has over the years focused specifically on two aspects of lupus: The effect(s) of sex hormones on the immune system during initiation/progression of lupus-like disease in mice, and the specific role played by type I interferons.
Elevated levels of serum type I interferons have been identified as a major feature of lupus and current clinical trials are testing the efficacy of targeting type I interferons in SLE patients. Using DTR-transgenic mice, we previously found that SiglecH+ plasmacytoid dendritic cells are key producer of type I interferon in B6.Nba2 mice and that specific ablation of this cell subset limits disease progression. Unfortunately, type I interferons are essential in our capacity to control viral and some bacterial infections, and thus a major concern of treatments targeting broad type I interferon production is a heightened susceptibility to infections. To determine pathogenic target cells of type I interferons in SLE, we developed type I interferon receptor (IFNAR) conditional KOs targeting B cells, T cells and myeloid cells. As expected, IFNAR-deficiency in B cells reduced disease severity including B cell hyperactivity, germinal center formation, and autoantibody production. IFNAR-deficiency in T cells surprisingly only affected a subset of T cells, while IFNAR-deficiency in myeloid cells.
Lupus is a devastating disease that can affect many organs. Neuropsychiatric lupus develops when the brain and CNS is affected and may present in different forms. Fatigue, cognitive impairment are common symptoms, while psychosis and demyelinating diseases are more rare. We recently discovered that the B6.Nba2 mouse model of lupus also develops neuropsychiatric lupus, as defined by anxiety, depression and cognitive impairment. Current efforts in the lab are focused on defining the role of TLR7 in both systemic lupus and neuropsychiatric lupus, as TLR7 is a well-known inducer of type I interferon production.
View publications for Trine Jorgensen, PhD
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Dr. Jorgensen and team have uncovered the role of S100a9 as a molecule integral in determining sex-specific immune responses in lupus.