Профессор Стэнфордского университета на ряде кафедр, включая кафедры биологических наук, неврологии и неврологических наук и нейрохирургии.
Как нейроэндокринолог занимается изучением стресса и дегенерации нейронов, а также разрабатывает стратегии генной терапии по защите чувствительных нейронов от болезней. Работает над методами переноса генов, исследуя задачу защиты нейронов от отрицательного влияния глюкокортикоидов.
Работы Сапольски широко отмечены в прессе, прежде всего — в специальном издании National Geographic "Стресс: портрет убийцы", в нескольких статьях в The New York Times, Wired Magazine и Stanford University Magazine. Также является автором ряда научно-популярных изданий.
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