Joan Cook-Mills, PhD, professor of Medicine in the Division of Allergy-Immunology, has had a longstanding interest in the regulation of inflammation. She completed her graduate training in biochemistry with an emphasis on immunology and micronutrient malnutrition at Michigan State University.
Her understanding of metabolism and nutrient regulation of cell signaling led her to study whether nutrients could be an effective and safe approach for regulation of chronic diseases, such as allergic inflammation, instead of current drug interventions.
Cook- Mills enjoys teaching and mentoring students in class and the lab, especially when she sees them increase their knowledge, get excited about their novel ideas and results and realize that they have an impact on discovery.
What are your research interests?
My primary interest is in the mechanisms of allergic inflammation and how nutrients regulate the signals for allergic inflammation.
What is the ultimate goal of your research?
The ultimate goal of my research is to understand the molecular mechanisms for regulation of inflammation by nutrients. Nutrients are chemical compounds that functionally interact with cell metabolism and cell signaling molecules, thereby regulating cellular function. The prevalence of allergic diseases and asthma has increased dramatically in the last 50 years in developed and developing countries. This time span is too short for genetic changes in populations, suggesting that there are environmental changes contributing to the increased prevalence in allergy and asthma.
How does your research advance medical science and knowledge?
We have discovered that different forms of vitamin E have opposite regulatory effects during inflammation. The alphalpha-tocopherol form of vitamin E inhibits allergic inflammation, but the gamma-tocopherol form of vitamin E increases allergic inflammation.
In the U.S., the average human plasma gammalpha-tocopherol concentration is five to seven times higher than most other countries, most likely due to gamma-tocopherol being rich in soybean oil, corn oil and canola oil – oils common in the North American diet. In contrast, oils prevalent in European and Mediterranean diets are rich in alpha-tocopherol such as olive oil, sunflower oil and safflower oil.
We reported that alpha-tocopherol associates with higher lung function and that gamma-tocopherol associates with lower lung function in a study of 4,500 individuals. In mouse models of allergic inflammation, alpha-tocopherol inhibited and gamma-tocopherol elevated allergic lung inflammation.
In mechanistic studies, we demonstrated that recruitment of inflammatory cells to the site of allergic inflammation was mediated through endothelial cell signaling by the receptor vascular cell adhesion molecule-1 and that this receptor activates signals including protein kinase C-alpha (PKC-alpha).
We further showed that alpha-tocopherol is an antagonist of PKC-alpha and that gamma-tocopherol is an agonist of PKC-alpha. As alpha-tocopherol and gamma-tocopherol represent modifiable risk factors, this may be an effective strategy for primary and/or secondary asthma prevention by dietary modification to lower gamma-tocopherol and increasealpha-tocopherol.
How is your research funded?
My research has been funded by the National Institutes of Health, the American Heart Association, Ray Biotech Inc. and the Ernest S. Bazley Asthma and Allergic Diseases Center Research and Education Program.
Where have you recently published papers?
Some of our recent manuscripts have been published in the Journal of Immunology, American Journal of Physiology-Lung Cellular and Molecular Physiology, American Journal of Respiratory Care and Critical Medicine, Respiratory Research and Biochemical Journal.
What types of collaborations are you engaged in across campus (and beyond)?
We collaborated with Rajesh Kumar, MD, professor of Pediatrics in the Division of Allergy and Immunology, Pedro Avila, MD, professor of Medicine in the Division of Allergy-Immunology and Kiang Liu, PhD, professor of Preventive Medicine in the Division of Epidemiology and Medicine in the Division of Internal Medicine and Geriatrics. I am currently collaborating with clinical investigators at Harvard and Vanderbilt for studies on the associations of alphalpha-tocopherol and gammalpha-tocopherol in children and outcomes of inflammation early in life.