[6] Takahashi was a postdoctoral fellow at the National Institute of Mental Health for two years under Martin Zatz before assuming a faculty position in Northwestern University's Department of Neurobiology and Physiology in 1983, where he held a 26-year tenure.
[6] Takahashi joined the faculty at the University of Texas Southwestern Medical Center at Dallas in 2008 as their Loyd B. Sands Distinguished Chair in Neuroscience.
[1] Takahashi also serves as a member of the Scientific Advisory Board of Hypnion Inc., a company focused on the development of novel therapeutics for central nervous system disorders affecting sleep and wake-alertness, as well as circadian rhythm abnormalities.
[12] Takahashi's research has led to many developments in understanding how the circadian clock of mammals affects physiology and relationships with the environment.
[14] After the in vitro research on the pineal gland culture system used to understand circadian oscillations, the limitations of the cell culture system were evident and Takahashi switched methods to begin using forward genetics and positional cloning—tools which required no advanced knowledge of the underlying mechanism—to understand the genetic and molecular bases of circadian rhythms.
[6][18] In 2000, Takahashi made what he calls one of his most significant contributions to the field, which was the cloning of the mutant tau gene identified in 1988 by Menaker and Martin Ralph.
[19] Since identifying the clock mutant in 1994,[17] Takahashi has continued his research on this mutation and has applied it to studying clinical disorders, such as irregular sleep homeostasis and obesity.
[6] Takahashi's lab has continued use of this method in order to lead to discoveries of the role of the circadian clock in vision, learning, memory, stress, and addiction, among other behavioral properties.
[6][2] In 2007, Takahashi and his colleagues at Northwestern ran a forward mutagenesis screen in mice looking for variations in circadian oscillations and subsequently identified a mutant which they named overtime (Ovtm).
[23] Using positional cloning, genetic complementation, and in-situ hybridization Takahashi and colleagues discovered that Ovtm was a point mutation that caused a loss of function in FBXL3 – an F-box protein – and was expressed throughout the brain and in the SCN.