Odunayo Susan Lawal, a second-year PhD student in the Clinical Translational Sciences Graduate Program, has been awarded an American Heart Association grant of $65,106 to support her research on the sex-specific role of damage-mediated signaling in the endothelial and immune homeostasis of pulmonary arterial hypertension (PAH).
PAH is a life-threatening disease that exhibits sexual dimorphism and lacks effective treatment options. Under the guidance of her mentor, Dr. Olga Rafikova, Susan will be investigating the contribution of the receptor for advanced glycation endproducts (RAGE) in PAH initiation and progression.
While RAGE mediates pro-survival and regeneration signaling, overactivation of RAGE has been suggested to promote pulmonary vascular remodeling. To better understand the role of RAGE in PAH, Dr. Rafikova’s team has generated a RAGE knockout (KO) rat and observed that male RAGE KOs spontaneously develop PAH, while female rats do not. This male-specific phenotype corresponds with a significant decrease in membrane CD31, a critical regulator of endothelial barrier integrity and immune cell maturation, in the lungs.
In this grant, Susan will be testing the hypothesis that the loss of CD31 predisposes males to impaired endothelial barrier integrity and increased activity of inflammatory cells. She also proposes that the elevated traffic of activated T cells through the impaired endothelial barrier elucidates the male-specific pro-inflammatory PAH phenotype discovered earlier by Dr. Rafikova's team. Therefore, correcting the impaired RAGE/CD31 signaling is expected to provide protection for males and form the basis for future sex-specific therapeutic approaches.
Ms. Lawal's long-term goal is to understand the mechanisms regulating endothelial/T-cell cross-talk and their sex-specific roles in PAH initiation and progression. This grant is a crucial stepping stone towards achieving this goal. With this funding, Susan will be able to conduct research that will contribute to closing the gap in knowledge surrounding PAH and provide a foundation for developing effective sex-specific treatments.