Dr. Kirk Pritchard Receives Grant Renewal to Continue Work to Improve Vascular Function in People with Sickle Cell Disease

Kirkwood Pritchard, PhD

Kirkwood Pritchard, PhD, professor of surgery (pediatric surgery), has been awarded a four-year, $2.2 million R01 grant renewal for the project titled, “Mechanisms of Inflammation in Sickle Cell Disease” from the National Heart, Lung, and Blood Institute.

Dr Pritchard's lab has shown that myeloperoxidase (MPO) and high mobility group box-1 (HMGB1) play important roles in the mechanisms by which sickle cell disease impairs vascular function. Dr. Pritchard’s lab designed L-acetyl-lysyltyrosylcysteine amide (KYC) to inhibit MPO.

Recently, he published that KYC is also a first-in-class systems pharmacology agent that improves vascular function and reduces liver injury in sickle cell disease (SCD) mice. As a systems pharmacology substrate, KYC enhances MPO catalase activity, which decreases oxidative stress and exploits MPO peroxidase activity to generate a new product that increases antioxidant gene expression.

Dr. Pritchard’s renewed NIH application employs state of the art molecular biology strategies to examine the mechanisms by which MPO and HMGB1 increase vasculopathy and vasocongestion in SCD mice. Findings from his studies may lead to new drugs to improve vascular function and reduce vasocongestion and stroke in people with sickle cell disease.

The project received funding from the Department of Surgery’s We Care Fund in 2015.