Tulane Center for Eosinophilia Disorders under the leadership of Dr. Anil Mishra, PhD, is a first center in the southern region of USA. The center will provide an opportunity to the researchers, patients and their families to understand the disease and consult for the better treatment of the eosinophil associated disorders. The center will also provide an opportunity to the basic research scientist to directly translate their experimental findings to the human disease with the help of clinicians. The center will be involved in basic, clinical and translational studies to determine the mechanistic aspects of eosinophilic disorders in the lung, skin and multiple gastrointestinal segments.
The center's aim is to develop diagnostic and therapeutic interventions for eosinophil associated allergic diseases. Eosinophilic disorders occur when eosinophils, white blood cells with a bilobed nucleus with multiple toxic granules white blood cell, are found in above-normal amounts in various parts of the body. Eosinophil resides in the gastrointestinal tract of healthy individuals https://www.jci.org/articles/view/6560 and https://www.jci.org/articles/view/10224; however, during allergic (food or aeroallergen) responses, a large number of eosinophils are generated from their precursors in bone marrow that move into the responsive organ of the body. We recently discover that the eosinophils generated during the allergic diseases are different then the eosinophils reside in healthy state. The pathogenic eosinophils that are generated in allergic condition and move to the diseased organs express cell surface molecules CD101 and CD274 https://www.jacionline.org/article/S0091-6749(18)30297-5/fulltext. These CD10+CD274+ eosinophils release a variety of toxins that can cause chronic inflammation, resulting in tissue damage.
We and others reported that eosinophils have a major role in promoting asthma, eosinophilic esophagitis (EoE) (https://www.sciencedirect.com/science/article/pii/S0016508507017994; https://www.nejm.org/doi/10.1056/NEJM199010113231505?url_ver=Z39.88-2003&rfr_id=ori:rid: crossref.org&rfr_dat=cr_pub%20%200www.ncbi.nlm.nih.gov) and a number of other gastrointestinal symptoms and tissue remodeling (fibrosis) and most recently found their accumulation and role in inflammation mediated pancreatic malignancy (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945222/). Because of the growing knowledge and a better diagnostic technology, we now have a better understanding of a number of allergic diseases. We are currently studying multiple compounds that might block eosinophil production and their recruitment into the tissues. Our research work indicated that in the future our center may provide the best treatment for eosinophil-associated multiple medical disorders such as asthma, eosinophilic esophagitis, and other eosinophil associated gastrointestinal disorders, including eosinophils-induced pancreatitis and malignancy.
Basic and Clinical Studies at Our Center
The major goal of Dr. Mishra's research is aimed to elucidate the mechanism inflammatory cells recruitment and their impact on immunological and pathological responses in eosinophilic gastrointestinal disorders [eosinophilic esophagitis (EoE) and eosinophilic gastritis (EG)], asthma, inflammatory cells induced pancreatitis, chronic pancreatitis and malignancies. Further, to translate the experimental findings into human novel therapeutic and diagnostic interventions. Dr. Mishra working in the area of inflammatory cells including eosinophils, mast cells, T cells biology from at least more than 2 decades and very much interested in defining the role of eosinophils in health and disease.
- Immune signaling molecules involved in promoting the pathogenesis of eosinophilic esophagitis (EoE). Recently, we first time implicated the role of IL-18 in eosinophils biology including maturing the naïve eosinophils into the CD101/CD274 double positive pathogenic eosinophils and these eosinophils have a critical role in promoting eosinophil associated gastrointestinal diseases (https://www.jacionline.org/article/S0091-6749(18)30297-5/fulltext) Currently, our current research is focused toward understanding the mechanisms that nerve cell derived VIP via its specific receptors present on eosinophils and mast cells have an important role on accumulation and activation in and beyond the esophageal epithelial mucosa that likely promotes pathophysiological functional abnormalities in eosinophilic esophagitis (EoE) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5736881/) Additionally, we are working on establishing the clinical significance of IL-18 and its responsive eosinophils in asthma. We hope by targeting the molecules responsible for transforming naïve eosinophils to pathogenic eosinophils we will provide therapeutic intervention for eosinophilic asthma and esophageal functional abnormalities in EoE. Below we show a summarized mechanistic schematic diagram of naive eosinophils generation, transformation to pathogenic eosinophils and their accumulation in EoE or asthma.
- IL-18 role in the progression of Chronic eosinophilic pancreatitis and pancreatic malignancy. Our other focused area of research is on the pathogenesis of acute and chronic pancreatitis including pancreatic malignancy.
Current Faculty and Postdoctoral Fellows
- Chandra Sekhar Yadavalli, Ph.D., joined Tulane Eosinophilic Disorder Center on Feb 1st, 2021, and is working on the "pathogenesis of acute and chronic eosinophil associated esophageal disorders". He received his Ph.D. degree from Bharathiar University in Coimbatore, India. Cell biology, Immunology, Molecular biology, and Biochemistry are his areas of specialization. Earlier, he worked as a Postdoctoral fellow at IISER Tirupati on the "NF-kB signaling pathway" from June 2019 to Jan 2021. He published nearly 28 articles in National and International journals.
- Chandra Sekhar Kathera, PhD. In 2022, he joined the Tulane Eosinophilic Disorder Center to work on MMP-12 Heterogeneity and Its Influence on Eosinophilic Esophagitis (EoE). Chandra Sekhar received his Ph.D. from Sri Venkateswara University in Tirupati, INDIA. He previously completed a Post-Doctoral Fellowship at Yeungnam University in South Korea in Recombinant Protein Purification and Lab Grown Meat Development Media Optimization. Between June 2021 and October 2022
