Klein-Seetharaman moved to the University of Pittsburgh as an assistant professor in 2002 and was promoted to associate professor in 2009. She joined the Warwick Medical School as a professor in medicine in 2013. She returned to the[United States in 2017, first as a professor at the Colorado School of Mines and then as a professor at the Arizona State University in 2021. Her research looks to uncover the structure-property relationships of membrane proteins.