by Samreen Jatana
Special to the CTSI Stories Blog
Lupus is a devastating disease that affects around 1 in 2,000 people in the U.S., and involves chronic inflammation and tissue damage in various organs including the skin, kidneys, and joints. Although the mortality rate for lupus has improved in recent decades, a diagnosis of lupus often means elevated risk of early mortality and lifetime of immunosuppressive therapy, which can carry significant side effects.
Anna Bird wants to improve treatment options. Bird, who is currently working towards a doctorate within the Immunology/Microbiology (IMV) graduate program in the laboratory of Jennifer Anolik, M.D., Ph.D., was recently awarded a CTSI Trainee Pilot Grant to study the immunologic mechanisms underlying the autoimmune disease, systemic lupus erythematosus (SLE).
Improving treatment options requires the development of more specific, targeted therapeutic approaches. But to make those improvements, researchers require a better understanding of the factors driving lupus pathogenesis, a project that Bird seeks to contribute to in her graduate research.
Specifically, she is using the CTSI Trainee Pilot as an opportunity to define the mechanisms underlying pathology observed in an under-characterized tissue in lupus: the bone marrow. Bone marrow in lupus often produces functionally abnormal or inadequate numbers of immune cells, and is a site where tissue necrosis and bone thinning are commonly observed. Evidence is accumulating that dysregulated cell production by the marrow contributes directly to lupus pathogenesis in peripheral tissues, as well as the high rate of infection that lupus patients experience.
Although it is poorly understood why lupus patients show marrow abnormalities, the work funded by the CTSI Trainee Pilot seeks to illuminate the mechanisms driving lupus pathogenesis within the bone marrow.
The CTSI project focuses on the neutrophil as a likely contributor to pathology in lupus marrow. Neutrophils contribute to inflammation in peripheral tissues including the vasculature and kidneys, and have been identified as a source of dying cell material and type I interferon, as well as B lymphocyte proliferation factors that are known to be central in driving B lymphocyte reactivity against self-tissues in lupus. Neutrophils develop abnormally in lupus and may be acquiring premature effector function that is responsible for elevated cell death seen in lupus marrow.
“Ultimately, this project will both assess whether neutrophils contribute to pathology in the marrow, as well as identifying the mediators responsible for abnormal neutrophil development in lupus,” said Bird. “This Pilot has provided a great opportunity for a translational investigation, incorporating a highly novel characterization of human bone marrow in lupus in combination with a murine model, which will allow me to tease apart the mechanisms underlying neutrophil defects in lupus.”
The CTSI Trainee Pilot has also provided a platform for collaboration between researchers in Hematology/Oncology, Immunology/Microbiology and the CTSI, as well as a foundation for generation of preliminary data that Anna can use to apply for the NIH K mechanism for future post-doctoral studies.