Research in the Nikolich-Zugich lab is centered on the biology of T lymphocytes in health, infection and aging, with a particular accent on immune defense. Our studies are performed in the context of the relationship between the immune system and microorganisms (acute and persistent pathogens and normal flora) over the lifespan, with particular emphasis on age-related defects in immunity, and defects in the long-term homeostasis of the immune system.
Diagnosis of the most critical primary defects in the aged innate and adaptive immune responses to multiple pathogen types (viral and bacterial, emerging pathogens) is coupled with studies to repair or ameliorate these defects by immunomodulatory intervention, immune rejuvenation or targeted, rational vaccine approaches. Our studies are often pursued by vertical model integration – using fundamental studies in rodents to identify specific age-associated dysfunctions and potential interventions, then translating these findings into relevant studies in humans (sometimes using non-human primates as an intermediary). In other cases, however, we start from human health and immunity issues, identify the key problems and then take that back to mice to dissect the fundamental principles, then validate our findings in humans. Thereby, we utilize both the bench-to-bedside and bedside-to-bench-to-bedside approaches.
We seek to elucidate the following key questions:
- Which T cell properties or functions are most critical for protective immunity against different infections?
- How are T cells maintained for life and why is their production and maintenance disturbed in old age?
- How is T cell activation and effector differentiation impaired during aging, and is this due to T cells themselves, to their partners in immune activation, their environment or a combination thereof?
- What can we do to fix (1-3) above, and do current and new longevity-extending interventions also improve (or harm) the function of the immune system?