The focus of the laboratory of James J. Lee, Ph.D., is on understanding the molecular and cellular mechanisms surrounding the immune responses associated with allergy, asthma and cancer.
Dr. Lee's approach to these problems extensively utilizes the mouse as a model system. In particular, his team exploits the generation of transgenic and knock-out mice as a method to study the differentiation and effector functions of eosinophils, a type of white blood cell (granulocyte) involved in host defenses to parasites. Eosinophils often increase in number as a consequence of allergic inflammation (for example, hay fever, asthma and so on).
Dr. Lee's team has created several novel mouse models of human diseases characterized by eosinophil infiltration of specific tissues. These mouse models allow for the molecular- and cellular-level characterization of the specific pathways leading to pathology.
Dr. Lee's laboratory collaborates extensively with Nancy A. Lee, Ph.D., at Mayo Clinic's campus in Scottsdale, Arizona, to achieve their experimental goals.
Molecular characterization of genes expressed in mouse eosinophils. In an attempt to understand regulatory pathways used to achieve a terminally differentiated cell type during murine hematopoiesis, Dr. Lee's research team is cloning genes that are expressed in the eosinophil and its progenitor cells. Eosinophils play pivotal roles in inflammatory responses to both infection and injury. These responses are mediated primarily through the expression of gene products specific to the eosinophil granule.
One of the laboratory's goals is the identification, characterization and cloning of the eosinophil granule protein genes in the mouse. The lab has isolated and cloned the genes that code for two of four major murine granule proteins and three eosinophil-associated granule ribonucleases. Studies of the transcriptional, and possibly coordinate, regulation of these genes during eosinophilopoiesis are ongoing.
- Development of improved mouse eosinophil models. The knockout mice described above will also permit a longer term goal of "humanizing" the mouse eosinophil. In this project, clones for the human granule proteins are used with eosinophil-specific promoters to generate transgenic mice expressing these human proteins. Selective breeding with the knock-out animals thus allows a tit for tat replacement of the mouse proteins with their human counterparts. The hope is that these studies will create mouse models much more characteristic of human disease.
- Animal models of eosinophil-mediated inflammation. Researchers in Dr. Lee's team are currently using transgenic and gene knock-out mouse models to examine the role(s) of eosinophils during immune-mediated inflammation. In addition, they are exploiting established murine models of respiratory inflammation to investigate the exacerbation of airway inflammation by environmental stimuli. These models include ozone exposure (a major air pollutant), allergen treatment and infection with the influenza virus, each of which exacerbates the symptoms of asthma patients.
Significance to patient care
Surprisingly, the role(s) of eosinophils in health and disease is often summarized by clinicians and basic research scientists as a pervasive consensus opinion first learned in medical or graduate school. Eosinophils are rare white blood cells whose activities are primarily destructive and are only relevant in parasitic infections and asthma.
Studies from Dr. Lee's laboratory investigating the role(s) of eosinophils in both health and disease have demonstrated that the activities of these granulocytes are far more expansive and complex than previously appreciated. In turn, this greater understanding has led to the realization that eosinophils have significant contributory roles in a wide range of diseases. Furthermore, the lab's published studies even implicate eosinophil-mediated activities in otherwise healthy persons.
- Board of directors, International Eosinophil Society, 2007-present
- Course director, Workshop on Phenotyping Mouse Models of Human Lung Disease, The Jackson Laboratory, Bar Harbor, Maine, 2007-present
- Co-editor, "Eosinophils in Health and Disease," 2012
- Member, Taskforce on the Research Needs of Eosinophil-Associated Diseases (TREAD), National Institutes of Health, 2012
- President, International Eosinophil Society, 2009-2011