The field of immunological investigation of tolerance mechanisms has been my main scientific pursuit since 1989. The long-term research goal of our laboratory is to define mechanisms of cells involved in immune tolerance. To achieve this, we focus on human immunological studies in allergy, asthma, and primary immunodeficiency. . I currently run a basic science laboratory at Stanford which includes 17 full time personnel and run a clinical research team at Stanford/Packard which includes 16 full time personnel who focus on clinical trials in allergy and asthma. By defining specific phenotype, functional, and molecular changes in a type of immune cell involved in tolerance, the regulatory T cell, we have been able to study and focus on these goals: 1) primary immune defects in tolerance, 2) environmental effects on tolerance, 3) immunomodulatory agents and their effect on tolerance. Our laboratory was the first to apply gene silencing experiments in human T cells to determine the roles of STAT5A and B in human immunology and signaling. Furthermore, we showed that polycyclic aromatic hydrocarbon (PAH), an airborne pollutant found in high levels in diesel exhaust, reproducibly causes the methylation of key genetic loci like FOXP3 in Treg. We also demonstrated that this mechanism was dependent on the aryl hydrocarbon receptor. Recently, we developed a new possible basophil-based diagnostic and epigenetic-based prognostic in which certain genetic loci in immune cells can be tracked for durable response to immunotherapy in near-fatal allergies. Our laboratory has published over 112 peer-reviewed papers and we continue to research mechanisms in human immunology through hypothesis-based and hypothesis-generating scientific discovery. I am very thankful for the opportunity and privilege to lead , collaborate with others, and mentor researchers in order to make transformative changes in patients’ lives in allergy and asthma through innovation and discovery.