Labs

Research Description

The goal of the Berin Lab is to advance the prevention and treatment of food allergy through understanding mechanisms of allergy and tolerance to foods. We study immune responses during clinical trials for food allergy to understand the immune basis of the treatment response. By identifying the immune response of those who develop treatment-based tolerance, our objective is to develop better therapies for all. We are particularly interested in T cells, a cell type that communicates with other cell types to drive antibody responses and inflammation. Immunotherapies that target T cell products are now the focus of several clinical trials for food allergy.

Food allergies can be classified into those mediated by the antibody IgE and those not mediated by IgE. Food protein induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy that we have been studying for several years and have discovered to be associated with activation of innate immunity. We are working to understand how foods are recognized by the immune system in FPIES. 

Food allergy often develops in the first year of life, and reactions commonly occur the first time that the child eats the food. Our lab is working to understand what factors are responsible for the onset of food allergy in early life. For those who develop food allergy later in life, we are studying the factors that are involved in breaking tolerance to a food that has been eaten many times previously.

For lab information and more, see Dr. Berin's Faculty Profile

Publications

See Dr. Berin's publications on PubMed.

Contact

Email Dr. Berin

Lab Staff

Abby Gubernat

Senior Research Technologist

Lisa Hung, PhD

Postdoctoral Fellow

Brianna Zientara

Research Technologist II

Research Description

The Eisenbarth-Williams lab focuses on defining the cellular and molecular mechanisms that regulate antibody responses. The development of these antibodies relies on the interactions between three immune cells – dendritic cells (DCs), T cells and B cells. We study how these three cell types communicate to shape different types of antibody responses, some protective in the case of vaccination and some harmful in the case of allergy and alloimmunization. By utilizing human samples to guide our studies and mouse models to test new mechanistic paradigms, we have identified novel and unexpected cell subsets and functions. The fundamental principles governing the interaction between DCs, T cells and B cells are the same across these seemingly disparate responses, yet specialization in the subset of each cell type, the specific niche for the interaction and the cellular signals exchanged between the cells dictates what type of antibody response is generated. This knowledge can be harnessed to induce protective immune responses and subvert pathogenic ones. Our recent work has also led us to focus on how the epithelium of the gut and lung regulate these responses, in particular to food allergens and aeroallergens.

More information on current work in the lab and our group can be found at the lab website: https://eisenbarthlab.squarespace.com

 

Publications

See Dr. Eisenbarth's publications on PubMed.

See Dr. Williams publications on PubMed.

For more information, visit the faculty profile page of Dr. Stephanie Eisenbarth and Dr. Adam Williams

Contact

Email Dr. Eisenbarth

Email Dr. Williams

The Kato Lab primarily focuses on the mechanism of type 2 inflammation in airway inflammatory diseases in humans. Currently, we use chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) as a model disease of type 2 inflammation. CRS is an inflammation of the nose and sinuses that blocks the air passages, causes headache and leads to loss of sleep, depression and reduced quality of life. CRSwNP which is a severe case of CRS, is well characterized by tissue eosinophilia with high levels of type 2 cytokines including IL-5 and IL-13. However, the mechanisms of type 2 inflammation in nasal polyps are still not well understood. The Kato Lab is currently focused on an epithelial-derived cytokine, TSLP (thymic stromal lymphopoietin), that is an IL-7-like cytokine molecule and is now recognized as an important regulator of type 2 inflammation in nasal polyps. We recently identified that TSLP is highly up-regulated in nasal polyps. TSLP is known to directly and indirectly induce type 2 inflammation via the activation of dendritic cells, Th2 cells, group 2 innate lymphoid cells (ILC2s) and mast cells which are all elevated in nasal polyps. My laboratory is currently investigating the role of Th2 cells, ILC2s, mast cells and dendritic cells in the amplification of type 2 inflammation and how TSLP contributes to type 2 inflammation through these cell types in nasal polyps.  In contrast to CRSwNP, inflammatory patterns in non-polypoid CRS (CRSsNP) are much less understood. Recently, the PI’s laboratory fully characterized patterns of inflammatory cytokines in the nasal mucosa of control subjects and patients with CRS. We found that CRSsNP displays heterogenous inflammation and this heterogeneity in CRSsNP might be responsible for the inconsistency of results in CRSsNP-related studies.  We are also currently working on understanding the effect of inflammatory endotypes on clinical phenotypes in CRSsNP.

Publications

See Dr. Kato's publications in PubMed.

For more information, view the faculty profile for Atsushi Kato, PhD.

Research Description

The Kuang Lab investigates the role of eosinophils and lymphocytes in eosinophilic gastrointestinal disease (EGID), as well as a variety of other eosinophilic disorders such as medication-induced eosinophilia vs. DRESS and hypereosinophilic syndromes (HES). We create well-characterized patient cohorts and collect both clinical data and biological samples from human research subjects.

Eosinophilic gastrointestinal disorders (EGIDs) of the upper GI tract are predominantly food-triggered chronic eosinophilic disorders with profoundly negative impact on quality of life. When left untreated, both eosinophilic esophagitis and eosinophilic gastroenteritis lead to progressive scarring of the affected GI tract segments. Predictive, non-invasive diagnostic testing and treatments are sorely lacking. Two types of immune cells, eosinophils and specialized T cells, have long been implicated in EGID pathogenesis, but numerous questions remain unanswered about their roles.

The GI tract is the largest repository for tissue eosinophils but many other eosinophilic disorders accompanied by excessive blood eosinophilia do not present with GI symptoms. Similarly, these specialized T cells, initially attributed to EGID, are recently thought to be biomarkers in food allergy and hay fever, conditions clinically distinct from EGID. Preliminary evidence suggests there are unique blood eosinophil signatures in EGIDs that distinguish them from blood eosinophils in other eosinophilic disorders, and that specialized circulating Th2 cells in EGIDs differ from those identified in more traditional IgE-mediated atopic conditions.

Our goals are to define 1) unique blood eosinophil signatures in EGID that distinguish it from other eosinophil-associated disorders or atopic disorders with blood eosinophilia; 2) Precisely identify the specialized Th2 cells in EGID as compared to food allergy. Findings will deepen our understanding of EGID pathogenesis, provide potential non-invasive EGID-specific diagnostic or disease activity biomarkers, and transform how one conceptualizes disease pathogenesis in other eosinophilic disorders (e.g. allergic asthma) and food-associated disorders (e.g. food allergy).

Select Publications

See Dr. Kuang’s publications in PubMed

For more information, visit the faculty profile page of Fei Li Kuang, MD PhD here

Contact

 Email: Dr. Kuang  feili.kuang@northwestern.edu

Lab Staff

Richard Kasjanski

Research Technician

Email: Richard rkasjanski@northwestern.edu

Our primary research interest is the regulation of immune cell survival and function by members of the Siglec family of receptors. These receptors bind to glycan ligands that include the negatively charged sugar known as sialic acid, and most bear cytoplasmic signaling motifs (ITIM and ITIM-like motifs) that initiate inhibitory signaling cascades to shut off inflammatory responses. Because each member of the Siglec family is expressed only a particular set of immune cells, these receptors represent promising therapeutic targets to reduce or prevent inflammatory responses involved in disease. We are especially interested in the use of Siglec-8 (expressed on eosinophils, mast cells, and, to a lesser extent, basophils) and Siglec-6 (expressed on mast cells and basophils) as targets to treat diseases and conditions caused by these cell types, such as allergic diseases, chronic spontaneous urticaria, and systemic mastocytosis. We have shown that antibody ligation of Siglec-8 on cytokine-primed eosinophils leads to cell death through a pathway involving the upregulation and activation of CD11b/CD18 integrin and ROS production. We are currently working to determine why cytokine priming is necessary for this effect and delineate the mechanism and consequences of Siglec-8-induced cell death. We have also established that antibody engagement of Siglec-6 on human mast cells leads to a broad inhibitory effect that is strengthened through co-engagement with an activating receptor of interest. This approach could give rise to focused strategies to shut off only a certain disease-causing pathway on mast cells without globally depleting these cells or inhibiting their function. Understanding the underlying biology of these receptors may improve our ability to exploit these receptors for therapeutic benefit, identify other molecules or pathways that may be therapeutically significant, or detect failures of these regulatory pathways that may lead to disease. The lab employs in vitro systems to assess the consequences of engaging these receptors on human eosinophils and mast cells and has generated unique transgenic mice to understand the functions and clinical utilities of these receptors in vivo.

Through a collaboration with the laboratory of Tom Hope here at Northwestern, we are also investigating the interactions between HIV and human mast cells. We and others have demonstrated that mast cells can be infected by HIV and that intact, replication-competent virions are produced as a result of this infection. Because the nature of the viral reservoir during antiretroviral therapy is of particular interest to understand the chronic low-grade inflammation observed in people living with HIV that promotes premature aging and age-associated co-morbidities and to identify approaches that could eradicate the cellular reservoir of HIV, it is important to understand the consequences of HIV infection of mast cells. In this research, we employ both primary human mast cells as well as cell lines to assess effects of HIV infection on mast cell phenotype, function, and survival, and utilize mice bearing human immune cells to explore patterns of infection and the consequences thereof in vivo.

Publications

View Dr. O'Sullivan's publications at PubMed

For more information, visit the faculty profile of Jeremy O'Sullivan, PhD.

Contact

Email Dr. O'Sullivan

Lab Staff

Yun Cao, MS
Research Lab Manager 1
312-503-1396

Research Description

Aspirin Exacerbated Respiratory Disease (AERD) is also referred to as Samter’s Triad. This disease is clinically defined by the presence of chronic rhinosinusitis with nasal polyps, asthma, and an intolerance to medications that inhibit the cyclooxygenase-1 enzyme. When patients with AERD ingest certain non-steroidal anti-inflammatory drugs (NSAIDs) such as Aspirin or Ibuprofen they develop worsening nasal and respiratory symptoms that can be severe. Even in the absence of taking NSAIDs, patients with AERD on average have more severe sinus disease and asthma compared to patients that have either chronic sinus disease or asthma alone. The Stevens lab is currently investigating what cellular and molecular mechanisms may be contributing to this enhanced disease phenotype. In particular, the lab is focusing on the role basophils and eosinophils may have in promoting the chronic inflammation observed in the sinuses. Additionally, the lab is also investigating how specific mediators related to the 15-lipoxygenase metabolic pathway may contribute to AERD disease pathogenesis.

Publications

View lab publications here via PubMed.
For more information, visit the faculty profile page of Whitney Stevens, MD PhD here.

Contact

Email Dr. Stevens

Lab Staff:
Anna Staudacher, MS
Research Technician II
Email Anna