Natarajan Aravindan, PhD
The long-term goal of Dr. Aravindan’s research is to define the regulatory mechanisms mediated by NFkB in therapeutic intervention tumor progression and metastasis. Dr. Aravindan's laboratory has recently shown that forced inhibition of NFkB enhances IR-induced NB cell death and targeting NFkB with curcumin increases radiation therapy-induced cytotoxicity. His project, Targeted Immunoliposomal EF24 Against Rel Orchestrated Neuroblastoma Relapse and Metastasis, examines the efficacy of EF24, a synthetic analog of curcumin with enhanced cytotoxicity and improved physicochemical properties, with a neuroblastoma target using anti-GD2 targeted liposomes.
Using an NB xenograft model, Dr. Aravindan will determine: (Aim 1) whether RT could initiate PFC leading to a persistent activation of NFκB and subsequent survival advantage and initiation of clonal expansion; (Aim 2) whether IR regulated eNOS dependent NO activates MMP9 and to study its role in NFkB dependent MMP/TIMP imbalance, NB progression and metastasis; (Aim 3) the efficacy of EF24-IL=>GD2 in inhibiting IR-induced NFkB-TNFa cross signaling dependent persistent activation of NFkB mediated survival advantage and clonal expansion; and (Aim 4) the potential effect of EF24-IL=>GD2 in IR-inhibited eNOS-NO dependent MMP9 induced NFkB mediated NB progression and metastasis. On completion, this study will provide insight into the orchestration of NFκB after RT and its downstream response. Most importantly, this study could lead to the development of a “deliverable” to test in clinical settings to mitigate local failure and metastasis that could lead to a positive impact on NB patients.