Elizabeth A. Jacobsen, Ph.D.

Elizabeth A. Jacobsen, Ph.D., studies the immune mechanisms of inflammation.

In collaboration with James J. Lee, Ph.D., and Nancy A. Lee, Ph.D., both of Mayo Clinic in Arizona, Dr. Jacobsen has used novel mouse models of asthma to define novel immune regulatory roles for eosinophils (a type of white blood cell) in allergic asthma. In particular, she demonstrated that eosinophils recruit/activate dendritic cells, alter the polarization of T cells, and recruit T cells to the lung in mouse models of allergic asthma.

These findings have direct translational implications to current asthma therapies that target eosinophil depletion in patients. Eosinophils are hallmark cells found in the lungs and airways of allergic asthma patients. Although the medical textbooks often describe eosinophils as destructive cells, Dr. Jacobsen's research has demonstrated the eosinophils contribute to the immune environment of the lung and may be significant mediators of propagating both allergic asthma, and in their absence, neutrophilic asthma. Often both forms of asthma are treated with inhaled or oral corticosteroids to inhibit the inflammatory response. In some patients this form of treatment is ineffective for unknown reasons. Understanding the mechanisms of corticosteroid induced inhibition of inflammation in these forms of asthma and the cells that are targeted will have an a significant impact on better understanding patient therapies.

Focus areas

Dr. Jacobsen has expanded her novel findings described above to study several additional areas of research:

• Elucidating mechanisms of neutrophilic and corticosteroid-resistant asthma. Dr. Jacobsen demonstrated that in the absence of eosinophils, a Th17-polarized neutrophilic form of asthma predominates in mouse models of allergic asthma.
• Defining cytokines that alter dendritic cell-induced Th17-polarized neutrophilic asthma.
• Determining the role(s) of corticosteroids on individual white blood cells (for example, dendritic cells, macrophages, lymphocytes, neutrophils and eosinophils) in mouse models of neutrophilic asthma where the corticosteroid receptor is specifically deleted from these cells.

Significance to patient care

Dr. Jacobsen's translational studies are being completed in mouse models of asthma, as it permits a reductionist approach to clarify the individual cellular and molecular mechanisms that participate in the inflammation process. In addition, many of these assessments are not possible to complete in humans.

The short-term goal of her research is to understand the immune mechanisms of these diseases, while the long-term goal is to identify novel cellular and molecular biomarkers and targets for patients with neutrophilic asthma.

Moreover, Dr. Jacobsen aims to translate these mouse-model findings to better identify those patients who will respond favorably to corticosteroid therapy.