- The primary focus of my laboratory involves translational research with infants that are protected from developing allergic disease secondary to unique, but poorly defined, environmental exposures. Farming environments have been found to be protective against the development of allergic diseases on multiple continents and include epidemiologic findings from the dairy farming regions of Wisconsin. Allergic diseases are major public health problems in children and adults and are initiated in early childhood by poorly understood mechanisms that include alterations in immune maturation and association with severe viral respiratory infections. The goals of our currently funded study are focused on in-depth investigations to better define the immunologic and environmental profiles at the inception of allergic diseases. Two aims of this study seek to interrogate innate immune cell function using an innovative and sensitive approach optimized in our laboratory along with cutting-edge techniques to quantify Treg cell function. Results from this study will lead to a better understanding of the impact of farming environments on immune maturation and immune responses that protect against the development of allergic disease and significant respiratory viral infections. The long-term goal is to bring the farm “protective” factors to all infants in a primary prevention manner that would promote healthy immune maturation and overall improved health.
- Another area of investigation involves utilization of numerous murine models of T cell unresponsiveness and functional analysis of peripheral blood mononuclear cells from human subjects. CD25+ T regulatory (Treg) cells are a subset of CD4+ T cells with an anergic phenotype that suppress immune responses by a poorly understood mechanism. Treg cells develop in the thymus (thymically occurring) or in lymphoid tissue (induced). Ongoing work in my laboratory has demonstrated a link between GRAIL (RNF128), an anergy-related E3 ubiquitin ligase, and CD25+ Treg cells. Our studies suggest that GRAIL is expressed along a continuum in anergic T cells and suppressive T cells and exerts its effect through modulation of the actin cytoskeleton. Our laboratory has recently developed a novel conditional knockout mouse model to assist with characterizing the role of GRAIL in Treg cell biology and various immune responses. By understanding the molecular basis for induction and function of CD25+ Treg cells, directed approaches can be developed for therapeutic alternatives to varied disease states that result from inappropriate immune responses.
Al Dhaheri N, Wu N, Zhao S, Wu Z, Blank RD, Zhang J, Raggio C, Halanski M, Shen J, Noonan K, Qiu G, Nemeth B, Sund S, Dunwoodie SL, Chapman G, Glurich I, Steiner RD, Wohler …June 24, 2020
A team in the lab of James Gern, MD, including co-investigators Christine Seroogy, MD, Daniel Jackson, MD, and Sima Ratnamam, MD, was recently awarded a supplement to their ongoing U19 grant from the National Institutes …June 1, 2020
The Pediatrics Research Week 2020 Abstract Book is now available. University of Wisconsin Department of Pediatrics faculty, staff, fellows and residents submitted over 50 research abstracts for the virtual conference, which is taking place May 26-29, 2020. …May 21, 2020
1. Ascierto PA, Fox B, Urba W, Anderson AC, Atkins MB, Borden EC, Brahmer J, Butterfield LH, Cesano A, Chen D, de Gruijl T, Dillman RO, Drake CG, Emens LA, Gajewski TF, Gulley JL, Stephen …May 4, 2020
In response to COVID-19, the Department of Pediatrics’ annual Research Week will offer alternative programming to spotlight the scholarly work from its residents, fellows, faculty and staff. Through a mix of livestreamed lectures and interactive …April 28, 2020
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