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Pharmaceutical Sciences Dept.
Lee T. Todd, Jr. Bldg, Room 345

Dr. Graf's laboratory's research focus is on the relationships between obesity and changes in lipid and lipoprotein metabolism that link obesity to cardiovascular diseases and diabetes.

Our work largely centers on pathways that promote the active elimination of cholesterol from the body in a process termed “Reverse Cholesterol Transport”. Currently available therapies target cholesterol synthesis and absorption to reduce plasma cholesterol and lower the risk cardiovascular disease. However, an emerging body of work suggests that the flux of cholesterol through lipoproteins (LDL and HDL) is more relevant to cardiovascular disease than their absolute levels in plasma. In addition, research from our lab and others suggests that cholesterol in the liver may play an active role in the development of non-alcoholic fatty liver disease, a common complication of obesity.

A transport protein complex called ABCG5 ABCG8, or G5G8 for short, is expressed in both the liver and intestine and represents the major route for cholesterol elimination from the body. We have recently shown that the loss of this transporter worsens the development of fatty liver disease and that acutely increasing its levels can restore some aspects of liver function in a mouse model of obesity and fatty liver disease. Our data also suggests that the function of this pump is altered in the setting of insulin resistance and fatty liver. However, little is known about the mechanisms that govern these changes and the extent to which these changes affect the progression of disease. The goal of this project is to determine how this pump is regulated in the liver such that therapeutics can be developed to accelerate cholesterol elimination in the treatment of both cardiovascular and liver disease.

The second project focuses on the role of the intestine in cholesterol elimination. Classically, we think of the small intestine as an absorptive organ that provides the body with the nutrients extracted from our diets. However, it is clear that this organ is also important in cholesterol elimination and that other pathways independent of G5G8 contribute to sterol excretion. The goal of this project is to identify proteins within this alternate pathway and determine whether these are amenable to pharmaceutical development.



  • Physiology, Molecular Genetics, Cell Biology, Mouse Models
  • Cholesterol Metabolism: Absorption, Transport, & Elimination
  • Regulation of the primary cholesterol elimination transporter, ABCG5 ABCG8 (G5G8)

Education & Appointments


  • PhD Univ Of Kentucky
  • MS Univ Of Kentucky
  • BS Texas A & M University


  • Professor, Department of Pharmaceutical Sciences
  • Vice Chair, Pharmaceutical Sciences

We wish to remember and honor those who inhabited this Commonwealth before the arrival of the Europeans. Briefly occupying these lands were the Osage, Wyndott tribe, and Miami peoples. The Adena and Hopewell peoples, who are recognized by the naming of the time period in which they resided here, were here more permanently. Some of their mounds remain in the Lexington area, including at UK’s Adena Park.

In more recent years, the Cherokee occupied southeast Kentucky, the Yuchi southwest Kentucky, the Chickasaw extreme western Kentucky and the Shawnee central Kentucky including what is now the city of Lexington. The Shawnee left when colonization pushed through the Appalachian Mountains. Lower Shawnee Town ceremonial grounds are still visible in Greenup County.

We honor the first inhabitants who were here, respect their culture, and acknowledge the presence of their descendants who are here today in all walks of life including fellow pharmacists and healthcare professionals.