Trained as a pharmacologist, he first deciphered the mode of action of modafinil, amphetamines, and antidepressants on narcolepsy symptoms,[2] work that was done in close collaboration with Dr. Seiji Nishino.
Ten years later, this led to the discovery that mutations in the hypocretin (orexin) receptor 2 cause canine narcolepsy,[3] and that human narcolepsy was caused by an immune mediated destruction of the hypocretin (orexin) producing cells in the brain[4] Parallel work performed by Mashashi Yanagisawa, Christopher Stinton and colleagues subsequently showed that hypocretin (orexin) deficient mice also have narcolepsy.
[5] The autoimmune destruction of hypocretin (orexin) neurons in the hypothalamus was later shown by Han and Mignot to be at least partially precipitated by influenza A infections, notably the H1N1 2009 pandemic strain,[6] complementing findings made in Northern Europe following the H1N1 Pandemrix vaccination campaign.
He is an elected member of the Association of American Physicians and of the Institute of Medicine of the National Academy of Sciences.
For 2023 he was awarded the Breakthrough Prize in Life Sciences for discovering that narcolepsy is caused by the loss of a small population of brain cells that make a wake-promoting substance, paving the way for the development of new treatments for sleep disorders.