Ravinder Reddy Gaddam, PhD, a postdoctoral research fellow in the Vikram Lab, received a three-year, $231,000 Career Development Award from the American Heart Association (AHA). Gaddam’s application was in < 1 percentile. He previously earned AHA Postdoctoral Fellowships in 2018 and 2021. With this new AHA funding, Gaddam will uncover the therapeutic potential of novel endothelium-targeted gamma-peptide nucleic acid-based miR-122 inhibitor (e-γPNA-122-I) to treat diabetic vasculopathies under the mentorship of Ajit Vikram, PhD, and Kaikobad Irani, MD, both faculty in the Division of Cardiovascular Medicine.

Vascular disorders are common in diabetic patients and are preceded by endothelial dysfunction. One approach to effectively treat endothelial dysfunction is targeting microRNAs (miRs). In particular, miR-122 is an optimal target because its blood levels are elevated in patients with diabetes and positively correlate with the severity of cardiovascular disorders. However, the clinical translation of existing miR-122 inhibitors remains challenging because of their adverse effects. In a recent Journal of Medicinal Chemistry publication, Gaddam and his colleagues demonstrated the suitability of engineered molecules with peptide backbone and specific modifications to inhibit miR-122 and rescue diabetes-associated endothelial dysfunction efficiently and safely. The attractive attributes of these molecules include their improved specificity, stability, immune inertness, and safety.

Specifically, Gaddam will use the AHA Career Development Award funding to investigate how miR-122 promotes diabetes-associated endothelial dysfunction and high blood pressure by targeting miR-122. This project will use novel endothelium-homing and liver-sparing miR-122 inhibitors. Because of the novelty and applicability of this molecule, the University of Iowa Research Foundation filed a utility patent application in February 2023.

“An incredible mentorship and guidance from my primary and secondary mentors, Dr. Ajit Vikram, PhD and Prof. Kaikobad Irani, MD, helped me achieve this AHA Career Development Award,” Gaddam said. Gaddam thanked both mentors by adding, “the unconditional support and encouragement from Dr. Vikram and Prof. Irani over the last few years aided in reshaping my research career.” Dr. Gaddam is also thankful to co-mentor Raman Bahal, PhD, associate professor at the University of Connecticut, for generating this new class of molecules.