Labs

Research Description

The question of primary interest in my lab is why only select individuals, despite being genetically similar and living in the same allergen environment, are prone to developing allergic disease, and which processes drive this predisposition? To address this, we employ a systems biology approach and bioinformatics to explore whether there is underlying unity in the pathogenesis of seemingly disparate allergic diseases. By synthesizing large volumes of biological data, we link departures from homeostatic conditions (including changes in metabolic, developmental, and endocrine systems) at the epithelial barriers of the skin, gut, and airways with innate immune system responses as a possible suite of mechanisms driving initiation of allergic disease. Specifically, we are asking the following questions: Are allergic diseases at different barrier sites caused by common systemic processes? Do hormones (estrogen, androgen, growth hormones) maintain homeostasis of the mucosal barriers? Why are developmental pathways for maintenance of tissue homeostasis linked to early susceptibility of asthma? What is the impact of environmentally relevant xenobiotics (xenoestrogens, aromatic hydrocarbons) on epithelial barriers and priming of allergic responses?

Secondarily, I keep being fascinated by a cell type that is intimately tied into mucosal biology, and plays central roles in many aspects of allergic disease - the eosinophil. I am intrigued by the fact that aside from being destructive in allergy, eosinophils play prominent roles in homeostasis and assist in normal development of tissues and maturation of other cell types – however, these alternate aspects of eosinophil biology remain largely unexplored. In my lab, we are studying the nature of reciprocal interactions between eosinophils and the mucosa in health and disease by asking the following questions: When and why are eosinophils homeostatic in the mucosa? What is their role in priming of immune responses?

For lab information and more, see Dr. Berdnikovs' faculty profile

Publications

See Dr. Berdnikovs' publications on PubMed.

Contact

Email Dr. Berdnikovs

Phone 312-503-6924

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

Our primary research interests are in eosinophil- and mast cell-associated diseases, including asthma, hypereosinophilic syndromes and systemic mastocytosis. We have a particular interest and focus on understanding the function of Siglec-8, an inhibitory and sometimes pro-apoptotic receptor expressed on human eosinophils, basophils and mast cells and how it can be targeted for clinical benefit. Animal models are used to study its closest counterparts, such as Siglec-F. In studies involving carbohydrate biochemistry and glycoproteomics, the lab is isolating and characterizing potential glycan ligands for Siglec-F and Siglec-8. Finally, we are interested in food allergy and anaphylaxis and are exploring new ways to prevent allergic reactions in vitro and in vivo. 

Publications

View lab publications via PubMed. 

For more information, please see Dr. Bochner's faculty profile or view more information regarding our NHLBI-funded work.

Contact Us

Email Dr. Bochner
Phone 312-503-0068 or the Bochner Lab at 312-503-1396.

Lab Staff

Melanie C. Dispenza, MD, PhD
Postdoctoral Fellow
312-503-0066

Piper Robida, PhD
Postdoctoral Fellow
312-503-0066

Krishan Chhiba, BS
MD/PhD Candidate
312-503-8032

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

Rebecca Krier, MS
Research Lab Manager 1
312-503-8032

Jeremy O’Sullivan, PhD
Research Assistant Professor
312-503-0066

Soon Cheon Shin, PhD
Research Associate
312-503-1131

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

Research Description

1. We study a novel mast cell-specific receptor called MRGPRX2 and its mouse ortholog Mrgprb2. We have discovered an integral role for these receptors in allergic-type drug reactions (McNeil et al., Nature 519:237) and currently are assessing their roles in allergic, infectious, and auto-immune diseases. These receptors appear to mediate communication between mast cells and nerve cells, and also may detect pathogens directly, thus acting as innate immune sensors. The study of these receptors is expected to fill in many of the blanks in our understanding of mast cell biology, including the discovery of mast cell involvement in disorders not previously associated with these cells.
2. We study the causes of chronic itch in mouse models of skin diseases. Recent studies have identified the cytokine IL-31 as the primary pruritogen in moderate-to-severe atopic dermatitis (AD). Evidence suggests that IL-31 directly stimulates epithelial cells and nerve cells in the skin, but how each cell participates in itch and inflammation is unknown. We are investigating IL-31’s effects on both cell types. We also have uncovered novel instances of cross-talk between nerve cells and epidermal cells in promoting itch that we are pursuing further.
3. We are evaluating novel biomarkers that may help to identify distinct endotypes of skin diseases like AD, using mouse and human tissue.

Publications

View McNeil lab publications here via PubMed.

Contact

Contact Dr. McNeil at 312-503-0084.

Lab Staff:
Li Zhang, MD, PhD
Research Assistant Professor
312-503-0908
Email Dr. Zhang

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

Our group studies Chronic Rhinosinusitis, a disease of the nose and sinuses that affects over 30 million Americans.  Using tissue samples collected from patients undergoing surgery for Chronic Rhinosinusitis through our close collaboration with Clinical Allergists and ENT surgeons, we study the gene and protein expression profiles as well as resident immune cell populations that are altered in disease in order to identify and explore potential mechanisms of disease progression and identify targets for therapeutic development. This work has provided evidence of dysregulation of epithelial immune barrier function, innate immunity, fibrin deposition and adaptive immune responses as potential mechanisms of disease progression. In the realm of epithelial barrier, we are currently investigating the mechanism by which Oncostatin M drives epithelial barrier degeneration. Additional research in our lab is pursuing mechanisms of fibrin deposition and the contributions of alterations in the fibrin system to polyp formation. Other experiments are working to reveal the potential impact of abnormal B cell activation in polyps. Finally, we continue our long running exploration of the cellular and molecular mechanisms of anti-inflammatory actions of glucocorticoid steroids and the causes of apparent steroid resistance in selected individuals and diseases.

Publications

View Dr. Schleimer's publications at PubMed

For more information, visit the faculty profile of Robert Schleimer, PhD.

Contact

Contact Dr. Schleimer at 312-503-0076

Lab Staff

Roderick Carter
Senior Research Technician

Yan Feng
Visiting Scholar

Yoshimasa Imoto
Visiting Scholar

James Norton
Laboratory Manager

Kathryn Pothoven
Graduate Student

Lydia Suh
Senior Research Technician

Toru Takahashi
Visiting Scholar

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