The Hartwell Foundation has presented a 2014 Individual Biomedical Research Award to Case Western Reserve University School of Medicine researcher Brian A. Cobb, to support his efforts to prevent or reverse asthma.
Cobb, an associate professor of pathology, will receive a total of $300,000 during the next three years to research a pathway in the immune system that appears to suppress lung inflammation caused by the disease. Cobb was one of 12 award winners this year.
In addition, by winning the award, Case Western Reserve qualified to receive Hartwell funding for a postdoctoral fellowship that CWRU will designate. The fellowship will provide support for two years at $50,000 direct cost per year to an individual who holds a PhD and/or equivalent doctorate, enabling the recipient to pursue further specialized training in biomedical research as part of his or her professional career development.
Asthma has become the most common chronic condition in children nationally and is the leading cause of school absences, according to the Asthma and Allergy Foundation of America. The disease accounts for a quarter of all emergency room visits, costing more than $18 billion annually in direct costs alone.
Increases in asthma and other immune-mediated diseases in Western countries have been linked to changes in microbial exposure, with some researchers blaming the sanitizing of our homes, schools and offices. Increasingly, researchers are finding evidence that a healthy microbiome inside the gastrointestinal system appears to be essential to healthy immunities.
Cobb will build on a discovery he made with Case Western Reserve PhD student Jenny Johnson and pathology postdoctoral fellow Mark Jones last year. They found that when mice were exposed to a carbohydrate produced by the symbiotic bacterium Bacteroides fragilis, the mice were highly resistant to asthma. Exposure activates immune cells, called CD4+Foxp3— T cells, which suppress the inflammatory response in a manner dependent upon the anti-inflammatory cytokine IL-10.
“The protective response is initiated by the T cells, which produce a mediator that tells the local environment to resist the inflammatory/asthmatic response,” Cobb said.
Cobb’s first step in the new research is to identify the molecule that mediates the pathway leading to protection. Once identified, he hopes to use it to induce the immune system to regulate itself and shut down the inflammatory response leading to asthma. He plans to test if the molecule can trigger prevention of asthma in mice or, in mice models with established asthma, reverse the condition.
Early data suggests the molecule is a naturally occurring protein, not a steroid. That’s potentially good news for severe asthmatics, who, as a rule, fail to respond to corticosteroid treatments, and patients with moderate to severe asthma who receive long-term corticosteroid treatments to manage the condition. Corticosteroids come with a long list of possible side effects, including glaucoma, high blood sugar and increased blood pressure, osteoporosis and increased risk of infection.
In addition to treating asthma, Cobb believes the ability to trigger the pathway may be useful for treating lupus, rheumatoid arthritis, Type I diabetes, multiple sclerosis and other autoimmune or inflammatory diseases.
Because the research is just at the starting point; it had little chance of receiving funding from governmental sources, Cobb said.
“I very much appreciate the generous support and vision of the Hartwell Foundation,” he said.
Each year, the Hartwell Foundation invites a limited number of institutions nationally to hold an internal open competition to nominate candidates from their faculty who are involved in early-stage, innovative and cutting-edge biomedical research that has not yet qualified for significant funding from outside sources.
In selecting awardees from the nominations, the Hartwell Foundation takes into account the compelling and transformative nature of the proposed innovation, the extent to which a strategic or translational approach might accelerate the clinical application of research results to benefit children in the United States, the extent of collaboration in the proposed research, the institutional commitment to provide encouragement and technical support to the investigator, and the extent to which funding the investigator will make a difference.
Case Western Reserve has six scientists who are current or former Hartwell investigators:
- 2014 Roberto Galan, assistant professor of neuroscience for his work: “Cortical Network Dynamics and Epileptiform Activity in Autism: From Animal Models to Children.”
- 2012, Saptarsi Haldar, assistant professor of medicine, for his work on “Creating a New Treatment Approach for Duchenne Muscular Dystrophy.”
- 2011, Jennell C. Vick, assistant professor of psychological sciences, biomedical engineering and pediatrics, for his work on “Treatment for Severe Speech Disorders in Children: Identifying Target Consonant Movements for Use with Animated 3D Visual Feedback Software.”
- 2011, Jonathan E. Sears, assistant professor of ophthalmology and cell biology, for his work on “Treatment for Severe Speech Disorders in Children: Identifying Target Consonant Movements for Use with Animated 3D Visual Feedback Software.”
- 2007, M. Michael Wolfe, professor of medicine, for his work “”Peptide Replacement Therapy Using Transgenic Stem Cells Delivered to the Small Intestine.” (He received his Hartwell award at another institution before joining Case Western Reserve.)
Learn more about The Hartwell Foundation at thehartwellfoundation.org.
Applications are now being accepted for the next round of Hartwell Fellowships. To apply, visit research.case.edu/LimitedSubmissions/Hartwell2015.cfm