Mollie M Walton, MD

Clinical Assistant Professor of Pediatrics, University of Missouri-Kansas City School of Medicine

Full Biography

Mollie Walton, MD, Cardiology, received an $8,000 Summer 2024 Fellowship Award through the CM Clinical Fellowship Research Awards program. The funding is for Dr. Walton’s study, “MARFAN: Maximizing Atenolol Response through Functional Assessment iNvestigations amongst connective tissue disorders” and covers a project period of Sept. 1, 2024-Aug. 31, 2025.

Marfan syndrome (MFS) is a genetic disorder that affects the body's connective tissues, which support organs, bones, and other tissues. Aortic root enlargement is a common and progressive feature of MFS and is associated with life-threatening aortic root dissection.

To mitigate this risk, use of prophylactic anti-hypertensive drug therapy is recommended and the beta blocker, atenolol, is a drug of choice. Unfortunately, patients continue to have poor response to the drug therapy.

The human organic cation uptake transporters (OCT) 1 and 2, encoded by the SLC22A1 and SLC22A2 genes, respectively, are influx transporters involved in the uptake of atenolol, as well as the antidiabetic drug, metformin. 

The objective of this study is to determine the role of genetic variants (known as polymorphisms) on the cellular uptake and clearance of atenolol, which may affect drug disposition and clinical effect.

“This project characterizes the role of OCT1 and OCT2 on atenolol cellular uptake and tests the hypothesis that OCT1 and OCT2 proteins with genetic polymorphisms, when expressed in vitro, will result in altered cellular uptake of atenolol relative to the reference genotype” explains Dr. Walton.

This approach utilizes transiently transfected OCT1 and OCT2 cell assays to perform time-dependent atenolol uptake experiments to generate kinetics information. Transient transfection is a process that introduces nucleic acids, such as DNA or RNA, into cells for a limited time.

“My goal is to provide a better understanding of polymorphisms associated with OCT1 and OCT2 expression and function as a means to individualize pharmacologic therapy for atenolol, as well as other OCT1 and OCT2-dependent drugs utilized in cardiovascular patients,” said Dr. Walton. “The backbone of this study is a desire to deliver precision-based pharmacotherapy to this population with whom I regularly work.”