Research Award Recipients

Dr. Esen Sefik earned her undergraduate degrees in molecular, cellular, and developmental biology at Yale University. She then completed her PhD in immunology at Harvard University. She continued her training at Yale University as an HHMI Damon Runyon post-doctoral fellow. Currently, Dr. Sefik works as an associate research scientist in Dr. Richard Flavell’s laboratory, where she employs humanized mice to study chronic inflammatory human diseases, including celiac disease.

Dr. Sefik is employing specially developed humanized mice that enable the development of a celiac disease-susceptible human immune system in mice to model new onset celiac disease in mice. These humanized mice provide factors in a physiological manner (considering time, location, and amount), enabling the development of most human hematopoietic cells, including human neutrophils, in mice. Additionally, this humanized mouse model incorporates essential cellular and molecular mechanisms associated with celiac disease, testing their role in celiac disease development. 

Dr. Sefik will be using this award to address the following aims:

1. Create and validate a new humanized mouse model as a surrogate for human celiac disease. 
2. Leverage these humanized celiac disease mice to characterize the disease, gain a real-time understanding of events, and identify key cellular and molecular pathways that drive human celiac disease pathogenesis.

Dr. Wenjun Zhang obtained his Ph.D. in Plant Genetics from the Institute of Genetics, Chinese Academy of Sciences, in 1994. He is a research specialist at the Dubcovsky Lab at the University of California at Davis where he studies wheat gene mapping and cloning. Dr. Zhang has generated a wheat gene deletion that eliminates all the alpha gliadins of wheat chromosome 6D, which are among the most allergenic gluten genes, but does not decrease the quality of breadmaking. Dr. Zhang is now using this deletion to develop new bread wheat varieties with reduced allergenicity. The new varieties are not yet celiac safe since they still have multiple sites that contain “bad” genes, but are an example of a possible pathway to keep reducing wheat allergenicity. Dr. Zhang has also generated a deletion of the a-gliadins on chromosome 6A and is using CRISPR to eliminate the “bad” a-gliadins on chromosome 6B. The fewer celiac epitopes the wheat product has, the lower the probability that it will trigger an allergenic response, which is expected to reduce the incidence of wheat intolerance in the population.

Dr. Wenjun Zhang and Dr. Jorge Dubcovsky aim to reduce wheat allergenicity by eliminating the wheat proteins that carry celiac epitopes with a long-term goal of developing bread and pasta wheat varieties that are safe for people with celiac disease.

Dr. Wenjun Zhang and Dr. Jorge Dubcovsky will be using this award to address the following aims:

1. Generate one pasta and one bread wheat without any celiac epitopes.
2. Make wheat generated in this project available to other researchers to promote the formation of a collaborative group of scientists working together to reduce wheat allergenicity and, in the long-term, develop a celiac-safe wheat.

The Celiac Disease Foundation is proud to fund a project at Dr. Jorge Dubcovsky’s lab at UC Davis to develop commercially viable celiac disease–safe wheat varieties for bread and pasta. Dr. Dubcovsky and Dr. Wenjun Zhang are continuing their work to change the DNA of wheat plants to incorporate synthetic gluten genes in order to produce this “celiac-safe” wheat. Further rounds of CRISPR (which is short for “clustered regularly interspaced short palindromic repeats” and is a type of DNA editing) are needed to remove those remaining genes that are not “celiac-safe.” Additionally, the team has begun creating and designing high molecular weight glutenin subunits (components that are responsible for gluten elasticity) to restore the breadmaking quality of the wheat. Read more on this exciting project here and here. 

Dr. Valérie Abadie received her undergraduate degrees in cellular biology and physiology at Paul Sabatier University, Toulouse, France. She next completed a Master degree in microbiology at Paris V-Necker Enfants malades and obtained her Ph.D. in Microbiology-Virology from the University of Paris VII in 2005.

Dr. Abadie is employing specially developed mice models that mimic celiac disease to learn if blocking B-cells can mitigate or prevent damage to the intestinal villi when someone with celiac disease ingests gluten to determine if B-cell targeted treatments for celiac disease should be developed.

Dr. Abadie and her team will be using this award to address the following aims:

1. Assess the contribution of B-cells to the activation and amplification of the anti-gluten CD4+ T-cell response
2. Determine whether targeting B-cells prevents IE-CTLs activation and development of villous atrophy

Dr. Abadie has published her finding that B-cells are required for the development of villous atrophy, supporting the study of B-cell-directed treatments for celiac disease.

• B Lymphocytes Contribute to Celiac Disease Pathogenesis

Dr. Jocelyn Silvester is an attending physician at Boston Children’s Hospital and an instructor of pediatrics at Harvard Medical School. Dr. Silvester chairs the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Celiac Special Interest Group. She completed her Ph.D. in Biology at the University of Cambridge, Cambridge, England prior to receiving her MD from Dalhousie University in Halifax, Nova Scotia, Canada in 2008.

Dr. Marisa Stahl is an attending physician at Colorado Children’s Hospital and an assistant professor of pediatrics at the University of Colorado School of Medicine. Dr. Stahl is a member of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Celiac Special Interest Group. She received her MD from Northwestern Univeristy The Feinberg School of Medicine in 2013, and completed her residency at the University of North Carolina in 2016 and her fellowship in pediatric gastroenterology at Children’s Hospital Colorado in 2019.

Dr. Silvester at Boston Children’s Hospital and Dr. Marisa Stahl at Colorado Children’s Hospital are collaborating to evaluate a potential new diagnostic test for celiac disease that could be an alternative to small intestinal biopsy. This test involves looking for changes in IL-2 in blood in a single-dose gluten challenge in children with celiac disease. Dr. Silvester and Dr. Stahl are also evaluating if blood may be exposed to gluten outside of the body, eliminating the need for patients to be consuming gluten to be diagnosed with celiac disease.

Dr. Silvester will apply the award to the following specific aims:

1. Establish whether change in serum IL-2 following gluten ingestion is a marker of celiac disease across the lifespan.
2. Determine whether ex vivo gluten-induced IL-2 release in whole blood is predictive of in vivo IL-2 response 4 hours after oral gluten challenge.
3. Assess whether there is boosting of ex vivo IL-2 response 1-4 weeks after a single gluten dose.

Dr. Benjamin Lebwohl is the Director of Clinical Research at the Celiac Disease Center at Columbia University and the President of the Society for the Study of Celiac Disease (SSCD). He received his MD from Columbia College of Physicians and Surgeons in 2003, and then completed his internship, residency, and chief residency in internal medicine at Columbia. He joined the faculty of the Celiac Disease Center at Columbia University in 2010.

Dr. Lebwohl and his team will seek to answer two critical questions in his research:

1. What happens to the diversity of the microbiome in celiac patients exposed to gluten and does it relate to the variance in the severity of symptoms suffered by this patient community; and
2. Using an epidemiological approach to a longitudinal Swedish database, has the relative mortality rate of celiac patients changed over time given higher diagnostic rates, improved access to gluten-free foods, and better patient awareness?

Dr. Lebwohl has published four articles with his findings that people with celiac disease have a slightly increased risk of mortality, psychiatric, and skin disorders, and that differences in the gut microbiome do not account for the diverse symptoms people with celiac disease experience.

• Association between celiac disease and mortality risk in a Swedish population
• Psychiatric disorders in patients with a diagnosis of celiac disease during childhood from 1973 to 2016
• Risk of skin disorders in patients with celiac disease
• Lack of Effect of Gluten Challenge on Fecal Microbiome in Patients With Celiac Disease and Non-Celiac Gluten Sensitivity