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From 2010 to 2014, Johnson served as the interim Chair of the Department of Preventive Medicine at UTHSC. In 2014, she was awarded the Kathryn Sullivan Bowld Endowment Fund Professorship in Women's Health from the College of Medicine at UTHSC. Johnson has been cited by Thomson Reuters as one of the most influential scientific publishers in the world.

Johnson has been a significant contributor to the university's research funding drives, bringing in $40 million toward her five on-going research projects. One of the projects, a Women's Health Initiative, began in 1993 and is evaluating diseases that effect women. The clinical trial involves more than 160,000 women. One of their findings was that women who consume two or more diet soft drinks each day face higher risks of heart problems than women who either don't drink them at all or drink them rarely. Another of her trials was the Systolic Blood Pressure Intervention Trial (SPRINT), which concluded in 2015. Its findings were that intervention could have a major impact on reducing blood pressure levels. Johnson is also the lead researcher on the Look AHEAD Study of the National Institute of Diabetes and Digestive and Kidney Diseases, which started in 2001 evaluating whether people with type 2 diabetes can prevent heart attack and other cardiovascular problems with weight loss and higher levels of physical activity. The study had been stopped in 2012, as preliminary indications of the 5,000 test subjects did not show positive changes from lifestyle intervention at the expected rates. Modifications in the program allowed it to be continued in 2014. In 2012, Johnson launched a clinic trial called TARGIT (Treating Adults at Risk for Weight Gain with Interactive Technology) funded by the National Institutes of Health. The program is designed to use iPod applications to support smoking cessation while eliminating weight-gain. In 2014, she began working on the D2d Trial (vitamin D and type 2 diabetes) aimed at determining if vitamin D intake lowers the risk of type 2 diabetes.

Karen C. Johnson (born 1955) is a research professor in the Departments of Preventive Medicine and Medicine in the College of Medicine at the University of Tennessee Health Science Center (UTHSC). She has been involved in at least five clinical world trials, including a Women's health initiative, the SPRINT Trial, the Look AHEAD (Action for Health in Diabetes) Study, the TARGIT Study and the D2d Trial. She has been noted by Thomson Reuters as one of the world's most-cited scientists.

Karen Lynn Chandler was born in 1955 in Memphis, Tennessee, to Colie Edward and Cecilia Chandler and grew up in Memphis, attending the Memphis Preparatory School. She continued her education earning an undergraduate degree at Lambuth University in 1978. She went on to earn her MD distinction at the University of Tennessee in 1985 and a Master of Public Health from Johns Hopkins University after her marriage. In 1990, she returned to her alma mater and joined the faculty of the UTHSC.